[{"id":256710,"date":"2026-09-25T00:00:40","date_gmt":"2026-09-25T04:00:40","guid":{"rendered":"https:\/\/www.thetransmitter.org\/?p=256710"},"modified":"2026-09-23T16:30:18","modified_gmt":"2026-09-23T20:30:18","slug":"grant-review-needs-reform-how-about-we-add-an-element-of-chance","status":"publish","type":"post","link":"https:\/\/www.thetransmitter.org\/funding\/grant-review-needs-reform-how-about-we-add-an-element-of-chance\/","title":{"rendered":"Grant review needs reform. How about we add an element of chance?"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"

A process that uses a lottery system saves time, reduces strategic resubmission and accepts that, above a quality threshold, luck has always played a part in science funding.<\/p>\n","protected":false},"author":73,"featured_media":256712,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","footnotes":""},"categories":[139],"tags":[170,107,40,207],"class_list":["post-256710","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-perspectives","tag-craft-and-careers","tag-funding","tag-policy","tag-science-and-society"],"acf":{"primary_tag":107,"doi_url":"","citation_count":"","custom_js_library":"","hero_type":"feat_image","hero_alt_image":null,"hero_youtube":"","hero_video":null,"hero_layout":"landscape","hero_caption":"Lucky roll:<\/strong> Lottery-based grant review has been adopted by grant funding initiatives in New Zealand, Switzerland and Germany. Adrien Peyrache and his colleagues are attempting to implement this model in a small sleep research program in Canada.","hero_by":"Illustration by","hero_credit":245526,"hero_bg_color":"tan","authors":[221737],"other_authors":"","related_title":"Explore more from The Transmitter<\/em>","related_hide":false,"related_filter":"latest","related_tag":null,"related_category":null,"related_custom":{"articles":null},"related_custom_wwn":{"articles":null},"newsletter":"","banner_content":"","banner_url":"","apple_article_id":"bb23ab75-4fd3-4c06-bd0f-4a12e67066e0","apple_article_revision":"AAAAAAAAAAD\/\/\/\/\/\/\/\/\/\/w==","google_button_text":"","google_btn_bg_color":"","tooltip_text":"","sidebar_related_hide":false,"sidebar_related_title":"related articles","sidebar_related_hide_images":false,"sidebar_related_articles":"","comps":[{"acf_fc_layout":"copy_comp","copy":"Like most of my colleagues, I not only benefit from publicly funded grants, but I also participate in the review and discussion of grant proposals.\u00a0<\/span>\r\n\r\nTwice a year at the Canadian Institutes of Health Research (CIHR), the Canadian equivalent of the U.S. National Institutes of Health, we discuss excellent applications and try to find consensus on a score, which will eventually determine whether a grant receives funding or not. During the most recent review session, I noticed that we were discussing some applications for the fourth or fifth time, but no funding decisions had been made. Do we really have to continue like this?\u00a0<\/span>\r\n\r\nAll of us\u2014reviewers, committee members, applicants\u2014had invested enormous time to get here. Accounting for all of that time, the real cost of peer-reviewed grant selection likely runs\u00a0<\/span>at least 40,000 Canadian dollars per application<\/span><\/a>, if not much more. With thousands of submissions at the CIHR alone, the scientific community is spending millions of dollars\u00a0deciding\u00a0who gets to do science, and not on doing more science. Ironically\u2014or tragically\u2014the system may eventually reach what is called the <\/span>Szilard point<\/span><\/a>, when the cost of the system exceeds its value.\u00a0<\/span>\r\n\r\nWe don't have to accept this as inevitable. It is time to rethink how the funding system is organized.<\/span>\r\n\r\nResearchers are good at evaluating bottom-tier applications and exceptional proposals. But when it comes to applications that are around the midline, determining which grant to score higher than another often seems like an impossible and highly arbitrary task. To save time and resources, why not let chance decide?\u00a0<\/span>\r\n\r\nThe idea of a lottery-based grant review process was proposed <\/span>more than a decade ago<\/span><\/a> and has been adopted by grant funding initiatives in New Zealand, Switzerland, Germany and elsewhere. So far, these communities <\/span>have welcomed the changes<\/span><\/a>. Chance may also make funding fairer, the German funding program shows: The <\/span>share of women<\/span><\/a> among both applicants and funded researchers increased in that system after the introduction of a lottery.<\/span>\r\n\r\nAdding a lottery element to the grant review process respects everyone's time, reduces strategic resubmission cycles and accepts that, above a quality threshold, luck has always been part of science. Before implementing these kinds of programs more broadly, however, we need to test them on a small scale and evaluate the results. That's exactly why we\u2019re trying it out in a small research program in Quebec.<\/span>\r\n\r\n[tt_sidebar_quote author='']Adding a lottery element to the grant review process respects everyone's time, reduces strategic resubmission cycles and accepts that, above a quality threshold, luck has always been part of science.<\/span>[\/tt_sidebar_quote]\r\n\r\n[tt_text class='']A[\/tt_text]\u00a0couple of years ago, my colleague <\/span>Nadia Gosselin<\/span><\/a> at the Universit\u00e9 de Montr\u00e9al and I started the Quebec Sleep Research Network, funded by the <\/span>Fonds de Recherche du Qu\u00e9bec \u2011 Sant\u00e9<\/span><\/a> (the regional biomedical funding agency). Our initiative aims to strengthen the sleep research community and foster dialogue among basic researchers, clinicians, policymakers and the public. Leading such an initiative not only lets us step outside the ivory tower but also try out alternatives in how science is managed, on a small scale.<\/span>\r\n\r\nOne of our core missions is to distribute small-value seed grants (CA$30,000) for projects that will eventually seek larger support, especially from the CIHR. During our first grant review session in 2025, we tried something different. We asked each reviewer (three per application) to give a simple\u00a0\u201dpass\u201d or \u201cfail\u201d on a grant,\u00a0based on explicit criteria. All passing grants then entered a\u00a0lottery, the fate of each decided by a roll of dice (in fact, its digital equivalent).\u00a0<\/span>\r\n\r\nThat\u2019s not all, though. We gave each reviewer the opportunity to flag one application as\u00a0\u201dunmissable.\u201d Any proposal that received two such flags went straight to the committee for direct funding, bypassing the lottery. Only one application received two unmissable flags in 2025, and it took the committee no time to agree that this application was truly exceptional. Finally, in keeping with our priority to support early-career researchers, we had an initial lottery just for them, ensuring that they received some of the grants in this review cycle. In the end, the committee met for less than an hour, and we were all satisfied with the outcome.<\/span>\r\n\r\nAs I write this, we are evaluating the 2026 call. For this second competition, we sought to improve the system even further. We are automatically carrying over grants that passed in 2025 but were not selected in the lottery. And we will not carry over any older proposals, as a two-year-old proposal may have become outdated. By preventing resubmission and re-review, we save even more time for everyone.<\/span>\r\n\r\nOf course, this system is not perfect, and a lottery is not the final answer to all the problems. Two alternative approaches include baseline funding and evaluation based only on someone\u2019s track record. Importantly, for large grants, we should not abandon discussing those proposals within study sections; a lottery system provides no feedback on how to improve an application for future competition. And a lottery alone cannot single out the most promising ideas, which is exactly why we designed our system such that exceptional proposals can skip the draw entirely.\u00a0<\/span>\r\n\r\nWe have received overwhelmingly positive feedback from the community so far, and not one colleague has objected to this system. Before the next call for applications, after two evaluation cycles, we plan to survey reviewers to ask if they felt the process was fair and whether they want it to continue. Many grant reviewers say they struggle to assign a fair score. So we also plan to ask the reviewers how much time they think they saved using a binary evaluation instead and whether this approach lessened the fear that a small scoring difference might result in dire consequences for the applicant. Unfortunately, our community is too small to include a control group of grants to evaluate traditionally, and we do not have prior review sessions for comparison. Instead, we need many more experiments across countries and agencies to assess the real impact of a lottery system.\u00a0<\/span>\r\n\r\nThe success of lottery-based grant review will not rely on proving that the projects we fund are better\u2014that may be impossible to show. Rather, its success will depend on developing a process that allows for good ideas to get a fair shot, in less time. <\/span>"},{"acf_fc_layout":"callout_comp","callout_title":"AI use disclosure:","callout_copy":"The author used Claude to check style against the guidelines and tighten phrasing before submission.","callout_color":"red"}]},"_links":{"self":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256710","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/users\/73"}],"replies":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/comments?post=256710"}],"version-history":[{"count":11,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256710\/revisions"}],"predecessor-version":[{"id":256736,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256710\/revisions\/256736"}],"acf:post":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/contributor\/221737"},{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/contributor\/245526"}],"acf:term":[{"embeddable":true,"taxonomy":"post_tag","href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/tags\/107"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/media\/256712"}],"wp:attachment":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/media?parent=256710"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/categories?post=256710"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/tags?post=256710"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}},{"id":256748,"date":"2026-09-25T00:00:03","date_gmt":"2026-09-25T04:00:03","guid":{"rendered":"https:\/\/www.thetransmitter.org\/?p=256748"},"modified":"2026-09-24T15:51:05","modified_gmt":"2026-09-24T19:51:05","slug":"fly-neurons-carry-molecular-signatures-of-their-origins","status":"publish","type":"post","link":"https:\/\/www.thetransmitter.org\/development\/fly-neurons-carry-molecular-signatures-of-their-origins\/","title":{"rendered":"Fly neurons carry molecular signatures of their origins"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"

The pattern of transcription factors a Drosophila<\/em> neuron expresses offers clues to its lineage and birth order\u2014and ultimately how neural circuits emerge.<\/p>\n","protected":false},"author":78,"featured_media":256750,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","footnotes":""},"categories":[152],"tags":[182,43,72,190,299,73,251,56,301,581,201],"class_list":["post-256748","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","tag-central-nervous-system","tag-circuits","tag-connectivity","tag-connectome","tag-development","tag-drosophila","tag-molecular-neuroscience","tag-neural-circuits","tag-neurons","tag-sex-differences","tag-transcriptomics"],"acf":{"primary_tag":299,"doi_url":"","citation_count":"","custom_js_library":"","hero_type":"feat_image","hero_alt_image":null,"hero_youtube":"","hero_video":null,"hero_layout":"landscape","hero_caption":"Decoder ring:<\/strong> Combinations of transcription factors, shown in various colors, distinguish neurons in the developing fruit fly ventral nerve cord according to the cells\u2019 birth order.","hero_by":"Erika Don\u00e0","hero_credit":"","hero_bg_color":"tan","authors":[250079],"other_authors":"","related_title":"Explore more from The Transmitter<\/em>","related_hide":false,"related_filter":"latest","related_tag":null,"related_category":null,"related_custom":{"articles":null},"related_custom_wwn":{"articles":null},"newsletter":"","banner_content":"","banner_url":"","apple_article_id":"57d834f2-5c02-4a5e-9fc0-b7fcf825ba69","apple_article_revision":"AAAAAAAAAAD\/\/\/\/\/\/\/\/\/\/w==","google_button_text":"","google_btn_bg_color":"","tooltip_text":"","sidebar_related_hide":false,"sidebar_related_title":"related articles","sidebar_related_hide_images":false,"sidebar_related_articles":"","comps":[{"acf_fc_layout":"copy_comp","copy":"How does a developing nervous system generate its vast array of neurons?<\/span>\r\n\r\nThe combination of transcription factors a neuron expresses provides some clues, according to two studies of <\/span>Drosophila<\/span><\/i> melanogaster <\/span><\/i>published in <\/span>Nature <\/span><\/i>over the past four months. This molecular code tracks two important aspects of a neuron\u2019s identity: its lineage and its birth order.\u00a0<\/span>\r\n\r\nThe two studies \u201care conceptually representing a way to understand how you can specify neural diversity,\u201d says <\/span>Claude Desplan<\/span><\/a>, professor of biology and neural science at New York University, who was not involved in the work.<\/span>\r\n\r\nBoth teams drew on adult <\/span>fruit fly connectomes<\/span><\/a>, using those wiring maps to relate neurons\u2019 molecular profiles during development to their eventual anatomy and connectivity.<\/span>\r\n\r\nDrosophila<\/span><\/i> is a good model for this kind of research because its nervous system is highly stereotyped, says <\/span>Denis Jabaudon<\/span><\/a>, professor of developmental neurobiology and plasticity at the Geneva University Neurocenter, who was not involved in the studies. The same neurons can be found in the same locations in all fruit flies.\u00a0<\/span>\r\n\r\nIt is well established that combinations of transcription factors help define neuronal identity, Jabaudon says, but how developmental patterning cues generate the right mix in each cell has been an open question.\u00a0<\/span>\r\n\r\n\u201cIt's a great step toward making the link between genetic programs, transcriptional programs and what a cell does and becomes,\u201d says <\/span>Lawrence Zipursky<\/span><\/a>, a neuroscientist at the University of California, Los Angeles, who was not involved in the studies.<\/span>\r\n\r\n[tt_text class='']O[\/tt_text]ne of the studies<\/span><\/a>, published in May, focused on well-characterized neurons in the cerebrum that control mating behaviors in male fruit flies. \u201cWe wanted to understand the origin of these unique neuron types that are built into these circuits that allow the fly to have specific behaviors,\u201d says study investigator <\/span>Josie Clowney<\/span><\/a>, associate professor of molecular, cellular and developmental biology at the University of Michigan.\u00a0<\/span>\r\n\r\nSingle-cell RNA sequencing revealed 89 transcription factors expressed in complex combinations that distinguished neuron families, or \u201chemilineages.\u201d Each family descended from a single stem cell and shared the same developmental fate, depending on whether the NOTCH gene had been on or off.\u00a0<\/span>\r\n\r\n[tt_sidebar_quote author='Josie Clowney']There are parts of the brain where it seems that the order the neuron is born is the most important thing for what that neuron is going to become.<\/span>[\/tt_sidebar_quote]\r\n\r\nNeurons in a given hemilineage typically resemble one another, send their neurites along a shared tract and use the same neurotransmitters, previous studies have shown. But lineage is only part of the story: The expression of another 36 transcription factors varied with neurons\u2019 birth order and the anatomy of their axons and dendrites, the researchers found.\u00a0<\/span>\r\n\r\n\u201cThere are parts of the brain where it seems that the order the neuron is born is the most important thing for what that neuron is going to become,\u201d Clowney says.\u00a0<\/span>\r\n\r\nThe other <\/span>study<\/span><\/a>, published in July, focused on the ventral nerve cord, which is analogous to the vertebrate spinal cord. The goal was to cover \u201cmany cells in the single cell transcriptomic landscape, to find that diversity that emerges in the connectome,\u201d says study investigator <\/span>Erika Don\u00e0<\/span><\/a>, a neuroscientist at the Consiglio Nazionale delle Ricerche.<\/span>\r\n\r\nBy sequencing more than <\/span>379,000 <\/span>cells from flies of four different developmental stages, the researchers created an atlas of gene expression in the nerve cord across development. From there, they identified the markers of 34 cord hemilineages and 17 transcription factors that encode neuronal birth order. Don\u00e0, who is Italian, was amused by the finding, as 17 \u201cis an unlucky number in Italy.\u201d<\/span>\r\n\r\nTogether, these factors act like a molecular time stamp, carrying information about when a neuron was born, and could potentially \u201cexplain a large degree of diversity,\u201d Don\u00e0 says.<\/span>\r\n\r\nArtificially expressing one factor outside its normal temporal window changed the neurons\u2019 molecular identity, morphology and projections, the team showed\u2014evidence that the code helps shape what kinds of neurons develop.\u00a0<\/span>\r\n\r\n[tt_text class='']M[\/tt_text]any of the transcription factors identified in the two studies do not disappear once a neuron has acquired its identity. Instead, they are expressed into adulthood, suggesting that they may also help a cell maintain its identity later in life. One possibility is that \u201cmaybe, evolutionarily, it was just cheaper to leave them on,\" Zipursky says.\r\n\r\nTogether, the two studies point toward a layered model of neuronal identity. First, a hemilineage-specific gene-expression code establishes a neuron\u2019s broad family and overall anatomical plan. A birth-order code then helps generate different subtypes within that family.\u00a0<\/span>\r\n\r\n\u201cTo me, it\u2019s very profound that you have the clock\u2014which, all the cells are following the clock\u2014and they integrate whatever their specification is into that clock,\u201d Zipursky says.\u00a0<\/span>\r\n\r\nSex-specific factors further refine neuronal identities rather than creating entirely distinct types, both studies suggest. Clowney compares this layer to \u201cgetting dressed\u201d\u2014the final accessory added to an outfit.<\/span>\r\n\r\nDecoding these layers could ultimately reveal how developmental genes guide the wiring of neural circuits, Jabaudon says.<\/span>\r\n\r\nBut whether a similarly systematic code exists in vertebrates remains unclear. The next step might be to try the same experimental methods in rodents, Don\u00e0 says. \u201cIt's going to be possible if people maybe can focus on two or three lineages and at very high resolution,\u201d she says. \u201cAnd, of course, it's very expensive because it's going to need a lot of cells to be sequenced, but it's doable.\u201d <\/span>"}]},"_links":{"self":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256748","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/users\/78"}],"replies":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/comments?post=256748"}],"version-history":[{"count":4,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256748\/revisions"}],"predecessor-version":[{"id":256759,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256748\/revisions\/256759"}],"acf:post":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/contributor\/250079"}],"acf:term":[{"embeddable":true,"taxonomy":"post_tag","href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/tags\/299"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/media\/256750"}],"wp:attachment":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/media?parent=256748"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/categories?post=256748"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/tags?post=256748"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}},{"id":256673,"date":"2026-09-24T00:00:58","date_gmt":"2026-09-24T04:00:58","guid":{"rendered":"https:\/\/www.thetransmitter.org\/?p=256673"},"modified":"2026-09-23T15:48:04","modified_gmt":"2026-09-23T19:48:04","slug":"polarized-cortical-organoids-mimic-the-brains-regional-organization","status":"publish","type":"post","link":"https:\/\/www.thetransmitter.org\/spectrum\/polarized-cortical-organoids-mimic-the-brains-regional-organization\/","title":{"rendered":"Polarized cortical organoids mimic the brain\u2019s regional organization"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"

The organoids show region-specific gene-expression changes that match those observed during fetal development.<\/p>\n","protected":false},"author":73,"featured_media":256675,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","footnotes":""},"categories":[152],"tags":[17,59,31,148,39,197],"class_list":["post-256673","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","tag-autism","tag-fragile-x-syndrome","tag-gene-expression","tag-methods","tag-organoids","tag-spectrum"],"acf":{"primary_tag":197,"doi_url":"","citation_count":"","custom_js_library":"","hero_type":"feat_image","hero_alt_image":null,"hero_youtube":"","hero_video":null,"hero_layout":"landscape","hero_caption":"Heads or tails:<\/strong> Cortical organoids treated with different signaling molecules express molecular markers of the anterior (green) or posterior (red) cortex.","hero_by":"","hero_credit":"","hero_bg_color":"tan","authors":[107413],"other_authors":"","related_title":"Explore more from The Transmitter<\/em>","related_hide":false,"related_filter":"latest","related_tag":null,"related_category":null,"related_custom":{"articles":null},"related_custom_wwn":{"articles":null},"newsletter":"","banner_content":"","banner_url":"","apple_article_id":"e3d9db66-1dc6-44a1-a64e-35082e90fbea","apple_article_revision":"AAAAAAAAAAD\/\/\/\/\/\/\/\/\/\/w==","google_button_text":"","google_btn_bg_color":"","tooltip_text":"","sidebar_related_hide":false,"sidebar_related_title":"related articles","sidebar_related_hide_images":false,"sidebar_related_articles":"","comps":[{"acf_fc_layout":"copy_comp","copy":"A simple protocol produces organoids that display molecular features of the front or rear of the human cortex, according to a new <\/span>study<\/span><\/a>. The technique could provide better cell-based models of autism and other neurological conditions that involve region-specific changes, the study suggests.<\/span>\r\n\r\nBriefly exposing neocortical organoids to signaling molecules called morphogens prompts them to develop their own signaling centers, the study found. These centers activate developmental pathways and induce molecular markers of anterior or posterior identity that match those found in the prenatal cortex.<\/span>\r\n\r\n\u201cIt\u2019s a very significant step,\u201d says <\/span>Arnold Kriegstein<\/span><\/a>, professor of neurology at the University of California, San Francisco, who was not involved in the work. The brain is more highly regionalized than any other organ, he says, with the same cell type taking on different functions and forming different connections depending on its location.<\/span>\r\n\r\nDuring embryonic development, gradients of morphogens organize the cortex along an anterior-posterior axis. But most cortical organoids either lack this large-scale organization or must be\u00a0 <\/span>fused with separate, morphogen-secreting spheres<\/span><\/a> to create assembloids.<\/span>\r\n\r\nThe new technique instead stimulates organoids to form their own morphogen-secreting centers, avoiding the need to fuse tissues. It is \u201ca very straightforward method\u201d that is easy to replicate, says study investigator <\/span>Momoko Watanabe<\/span><\/a>, assistant professor of anatomy and neurobiology at the University of California, Irvine.<\/span>\r\n\r\nIn the new study, Watanabe and her colleagues generated neocortical organoids from human pluripotent stem cells. After 15 days, the team exposed them to a fixed concentration of either FGF8 or BMP4, morphogens that promote anterior or posterior identity, respectively.\u00a0<\/span>\r\n\r\nOrganoids incubated with FGF8 for six days showed increased expression of anterior markers and formed FGF8-secreting clusters that signaled to nearby cells, helping to establish and maintain anterior identity. Similarly, organoids treated with BMP4 showed increased expression of posterior markers and developed posterior signaling centers that remained detectable at week 14, the study found.<\/span>\r\n\r\nThe polarized organoids also showed shifts in gene expression along the anterior-posterior axis that matched those observed during fetal development.\u00a0<\/span>\r\n\r\n[tt_sidebar_quote author='Arnold Kriegstein<\/span>']It\u2019s a very significant step.<\/span>[\/tt_sidebar_quote]\r\n\r\n[tt_text class='']T[\/tt_text]hat graded pattern of gene expression is important, says <\/span>Irene Faravelli<\/span><\/a>, assistant professor of pathology and pathophysiology at the University of Milan, who was not involved in the study. \u201cThe developing human cortex itself is organized largely through molecular gradients rather than sharp distinctions between areas,\u201d she says.<\/span>\r\n\r\nBut molecular markers are just one component of regionalization, Faravelli adds. \u201cIn the brain, areal identity also involves differences in cellular organization, connectivity and function, including interactions with other brain areas and the presence of sensory inputs. These organoids do not reproduce that full environment.\u201d<\/span>\r\n\r\nWatanabe and her team also developed cortical organoids from stem cells derived from people with fragile X syndrome, a common genetic cause of autism.\u00a0<\/span>\r\n\r\nCompared with control organoids, the fragile X models showed weaker gradients in the transcription factors SOX4 and SOX11 along the anterior-posterior axis. These findings mirror transcriptional changes that follow an anterior-posterior gradient detected in a <\/span>previous analysis<\/span><\/a> of cortical tissue from people with autism, highlighting the organoids\u2019 potential to study region-specific changes linked to neurodevelopmental conditions.<\/span>\r\n\r\nThe findings were published this month in <\/span>Cell Stem Cell<\/span><\/i>.\u00a0<\/span>\r\n\r\nIn addition to modeling neurological conditions, the organoids could help resolve the protomap-protocortex debate\u2014that is, the extent to which cortical organization is preprogrammed or driven by external factors, such as incoming signals from the thalamus. The fact that cortical polarity can emerge without external input suggests that intrinsic programs initiate regionalization, Watanabe says. But refining those regions likely requires external inputs, which become increasingly important after birth, she says.<\/span>\r\n\r\nWatanabe and her team next plan to analyze the organoids beyond week 14, a stage that roughly corresponds to the third trimester of fetal development. By then, they expect to see more distinct patterns of molecular markers corresponding to more mature cortical organization, she says. In the long term, they would also like to investigate whether neuronal activity\u2014measured using electrophysiology or calcium imaging\u2014differs between anterior and posterior cortical organoids, she says.<\/span>"}]},"_links":{"self":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256673","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/users\/73"}],"replies":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/comments?post=256673"}],"version-history":[{"count":3,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256673\/revisions"}],"predecessor-version":[{"id":256722,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256673\/revisions\/256722"}],"acf:post":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/contributor\/107413"}],"acf:term":[{"embeddable":true,"taxonomy":"post_tag","href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/tags\/197"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/media\/256675"}],"wp:attachment":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/media?parent=256673"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/categories?post=256673"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/tags?post=256673"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}},{"id":256688,"date":"2026-09-23T12:24:16","date_gmt":"2026-09-23T16:24:16","guid":{"rendered":"https:\/\/www.thetransmitter.org\/?p=256688"},"modified":"2026-09-23T15:45:17","modified_gmt":"2026-09-23T19:45:17","slug":"prefrontal-cortex-has-three-transcriptomic-acts-across-human-lifespan-new-atlas-suggests","status":"publish","type":"post","link":"https:\/\/www.thetransmitter.org\/transcriptomics\/prefrontal-cortex-has-three-transcriptomic-acts-across-human-lifespan-new-atlas-suggests\/","title":{"rendered":"Prefrontal cortex has three transcriptomic acts across human lifespan, new atlas suggests"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"

Various genes show distinct exits and entrances with age in the open-source dataset, the largest of its kind to date.<\/p>\n","protected":false},"author":78,"featured_media":256690,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","footnotes":""},"categories":[152],"tags":[146,228,37,201],"class_list":["post-256688","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","tag-alzheimers-disease","tag-psychiatric-disorders","tag-single-cell-sequencing","tag-transcriptomics"],"acf":{"primary_tag":201,"doi_url":"","citation_count":"","custom_js_library":"","hero_type":"feat_image","hero_alt_image":null,"hero_youtube":"","hero_video":null,"hero_layout":"landscape","hero_caption":"Sorting cells:<\/strong> Based on their single-nucleus transcriptomic patterns, cells from the prefrontal cortex of 1,494 people fall into eight classes, which were split into 27 subclasses and further into 65 subtypes.","hero_by":"Courtesy of PsychAD Consortium","hero_credit":"","hero_bg_color":"tan","authors":[235277],"other_authors":"","related_title":"Explore more from The Transmitter<\/em>","related_hide":false,"related_filter":"latest","related_tag":null,"related_category":null,"related_custom":{"articles":null},"related_custom_wwn":{"articles":null},"newsletter":"","banner_content":"","banner_url":"","apple_article_id":"e39c2636-745b-4438-81b9-e63a16b6ab43","apple_article_revision":"AAAAAAAAAAAAAAAAAAAAAg==","google_button_text":"","google_btn_bg_color":"","tooltip_text":"","sidebar_related_hide":false,"sidebar_related_title":"related articles","sidebar_related_hide_images":false,"sidebar_related_articles":"","comps":[{"acf_fc_layout":"copy_comp","copy":"All the dorsolateral prefrontal cortex is a stage and all the genes merely players; they have their exits and entrances across three acts divided by age, according to a new human <\/span>brain-cell atlas<\/span><\/a> published today in <\/span>Nature<\/span><\/i> along with eight companion studies.\u00a0<\/span>\r\n\r\nTurbulent changes related to neurogenesis and gliogenesis make for a dramatic first act leading up to adulthood. The second act, from early adulthood through middle age, is eerily silent, but a new cast of characters dominated by glia takes the stage for the third act, at around age 60, according to the atlas, which shows how gene activity changes in individual cells of the human prefrontal cortex over the span of a lifetime.\u00a0<\/span>\r\n\r\nThe data are <\/span>publicly available<\/span><\/a> and come from 1,494 people, who ranged in ancestry, health and psychiatric profiles and age, from before birth to more than 100 years. The studies reveal the nonlinear dynamics of disease progression and weakened clock-gene rhythms in people aged 60 and up, among other novel findings.\u00a0<\/span>\r\n\r\nThe work is a \u201cherculean effort\u201d that is \u201ctransformative for our understanding of the prefrontal cortex across the human lifespan, in neurodegenerative and psychiatric disease, and its genetic regulation,\u201d says <\/span>Jennifer Below<\/span><\/a>, professor of genetics at Vanderbilt University Medical Center. Below was not involved in the work but reviewed one of the companion papers<\/span>.\u00a0<\/span>\r\n\r\nThe atlas is \u201cthe largest resource with cellular resolution released to date,\u201d Below adds. Comparable datasets containing single-cell or single-nucleus transcriptomics have focused on specific <\/span>age groups<\/span><\/a> or <\/span>brain disorders<\/span><\/a>, or have smaller cohorts.<\/span>\r\n\r\n\u201cStudying disorders separately can obscure shared biology, while combining datasets generated using different methods can introduce technical differences that resemble disease effects,\u201d says study investigator <\/span>Panos Roussos<\/span><\/a>, professor of psychiatry and of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai.\u00a0<\/span>\r\n\r\nThe new dataset includes 500 people diagnosed with Alzheimer\u2019s disease, 112 with diffuse Lewy body disease, 85 with vascular dementia, 40 with Parkinson\u2019s disease, 47 with tauopathy, 15 with frontotemporal dementia, 120 with schizophrenia and 55 with bipolar disorder. Many of these people had multiple diagnoses.\u00a0<\/span>\r\n\r\n[tt_text class='']R[\/tt_text]oussos and his colleagues in the PsychAD Consortium<\/a> isolated single nuclei from dorsolateral prefrontal cortex tissue and conducted multiplexed single-nucleus RNA sequencing. They focused on the dorsolateral prefrontal cortex because it \u201ccontributes to working memory, planning, decision-making and cognitive control\u2014functions affected across many of the disorders we studied,\u201d he says.\r\n\r\nBased on genetic markers, they sorted the 6.3 million nuclei by cell type, including excitatory and inhibitory cells, astrocytes, immune cells, oligodendrocytes, oligodendrocyte progenitor cells and vascular support cells.<\/span>\r\n\r\nCell type accounts for 50.5 percent of the variation in the dataset; the second-largest source of variation was person-to-person differences. This result shows that \u201cnuclei from the same person are related observations,\u201d so researchers planning to use the dataset should avoid treating \u201ceach nucleus as an independent person,\u201d Roussos says.\u00a0<\/span>\r\n\r\n[tt_sidebar_quote author='Jennifer Below']The work is a \u201cherculean effort.\u201d[\/tt_sidebar_quote]\r\n\r\nNon-neuronal cells are more abundant than usual in the brains of people with neurodegenerative disorders, whereas deep-layer excitatory neurons are more abundant in people with neuropsychiatric disorders, according to an analysis using a <\/span>custom statistical tool<\/span><\/a>. The groups also differentially expressed some of the same genes, a <\/span>different statistical tool<\/span><\/a> demonstrated. Many of those genes are essential for cell function.\u00a0<\/span>\r\n\r\nDifferent cell types also follow specific trajectories over the course of disease progression, a neural network model revealed. This is a novel perspective, showing that gene-expression patterns change nonlinearly across disease progression and can even impact it, says <\/span>Michael Lutz<\/span><\/a>, professor of neurology and pathology at Duke University, who was not involved in the work but reviewed the paper.\u00a0<\/span>\r\n\r\nThe broad age distribution enabled the researchers to look at <\/span>transcriptomic changes through development and aging<\/span><\/a>. They found \u201cextensive developmental changes, followed by relative molecular stability through much of adulthood and renewed changes in later life, particularly in glial support and immune cells,\u201d Roussos says.\u00a0<\/span>\r\n\r\nClock genes associated with circadian rhythms are particularly dysregulated in people aged\u00a0 60 or older, an analysis of data from approximately 200 neurotypical adults revealed. These patterns were reconstructed from donors with different times of death, so they help \u201cgenerate hypotheses about circadian aging rather than directly measuring changes in an individual\u2019s sleep,\u201d Roussos says.\u00a0<\/span>\r\n\r\n[tt_text class='']T[\/tt_text]he dataset also represents people with different ancestries and underlying genetic traits, which the researchers mapped onto observed gene-expression patterns<\/a> and built models of how genetic variation shapes gene regulation. This pointed them to \u201cnew targets and potential mechanisms of risk that can be exploited to develop better drug therapies,\u201d Below says.\r\n\r\nHowever, \u201cmany groups were not represented, and there remains a lot of opportunity to expand such studies across populations and exposures,\u201d Below says.\u00a0<\/span>\r\n\r\nIt is the first time this kind of analysis has been applied to people of non-European descent at this scale, says <\/span>Seth Ament<\/span><\/a>, professor in the Department of Psychiatry and Institute for Genome Sciences at the University of Maryland School of Medicine, who was not involved in the study. The analysis included 439 people of non-European or mixed ancestry. It shows convergence across ancestry for \u201ccell-type-specific mechanisms, some of which we didn't know about,\u201d he says.<\/span>\r\n\r\nThe brains were collected postmortem, \u201cand what's present in that brain reflects the entirety of someone's life experience in some ways,\u201d says Ament, who reviewed the paper. For complex diseases, such databases are mainly useful for generating hypotheses and pointing to where researchers should be looking, he says. Ament and his colleagues posted a <\/span>preprint<\/span><\/a> in July describing changes in single-cell gene expression across different ages, representing more than 2 million cells.\u00a0<\/span>\r\n\r\nNext, Roussos says he wants to \u201cexpand across brain regions and populations, integrate gene expression with other molecular measurements, and test the mechanisms suggested by the atlas.\u201d<\/span>\r\n\r\nLutz says he plans to use the database in combination with other multi-omics atlases, such as <\/span>Rush Memory and Aging Project<\/span><\/a> and the <\/span>Alzheimer\u2019s Disease Neuroimaging Initiative dataset<\/span><\/a>, for orthogonal validation and to gain deeper insight into disease mechanisms.<\/span>"}]},"_links":{"self":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256688","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/users\/78"}],"replies":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/comments?post=256688"}],"version-history":[{"count":10,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256688\/revisions"}],"predecessor-version":[{"id":256724,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256688\/revisions\/256724"}],"acf:post":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/contributor\/235277"}],"acf:term":[{"embeddable":true,"taxonomy":"post_tag","href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/tags\/201"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/media\/256690"}],"wp:attachment":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/media?parent=256688"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/categories?post=256688"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/tags?post=256688"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}},{"id":256656,"date":"2026-09-23T00:00:50","date_gmt":"2026-09-23T04:00:50","guid":{"rendered":"https:\/\/www.thetransmitter.org\/?p=256656"},"modified":"2026-09-22T15:50:39","modified_gmt":"2026-09-22T19:50:39","slug":"microglia-scoop-out-garbage-from-inside-neurons","status":"publish","type":"post","link":"https:\/\/www.thetransmitter.org\/microglia\/microglia-scoop-out-garbage-from-inside-neurons\/","title":{"rendered":"Microglia scoop out garbage from inside neurons"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"

Through a newly identified process called skoupocytosis, neurons recruit the immune cells to remove cellular waste they find hard to deal with themselves.<\/p>\n","protected":false},"author":73,"featured_media":256664,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","footnotes":""},"categories":[152],"tags":[18,104,34],"class_list":["post-256656","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","tag-cellular-neuroscience","tag-glial-cells","tag-microglia"],"acf":{"primary_tag":34,"doi_url":"","citation_count":"","custom_js_library":"","hero_type":"video","hero_alt_image":null,"hero_youtube":"","hero_video":256663,"hero_layout":"landscape","hero_caption":"Offloading waste:<\/strong> Neurons may recruit microglia (green) to dispose of proteolytic organelles (red) and other waste packets if they become too large to squeeze through axons.","hero_by":"Video by Renee Pepper","hero_credit":"","hero_bg_color":"tan","authors":[235277],"other_authors":"","related_title":"Explore more from The Transmitter<\/em>","related_hide":false,"related_filter":"latest","related_tag":null,"related_category":null,"related_custom":{"articles":null},"related_custom_wwn":{"articles":null},"newsletter":"","banner_content":"","banner_url":"","apple_article_id":"4373b88e-a63c-41f7-83f3-57d7a3cb2595","apple_article_revision":"AAAAAAAAAAD\/\/\/\/\/\/\/\/\/\/w==","google_button_text":"","google_btn_bg_color":"","tooltip_text":"","sidebar_related_hide":false,"sidebar_related_title":"related articles","sidebar_related_hide_images":false,"sidebar_related_articles":"","comps":[{"acf_fc_layout":"copy_comp","copy":"Microglia are professional phagocytes, surveying the brain and cleaning up neuronal debris, damaged proteins and other biomolecules. The cells can also make contact with axons to scoop out large organelles containing degraded proteins, a new <\/span>preprint<\/span><\/a> shows.<\/span>\r\n\r\nThe study reveals a novel exit route for debris that neurons could call upon when needed, says <\/span>Ralph Nixon<\/span><\/a>, professor of psychiatry and cell biology at New York University, who was not involved in the work.<\/span>\r\n\r\nNeurons can eject their garbage into <\/span>extracellular spaces<\/span><\/a>. They can also package waste generated at presynaptic active zones into organelles and traffic them to the soma for degradation. Occasionally, in stressed or active neurons, these proteolytic organelles can get too bloated to make it through the axon, says study investigator<\/span> Shigeki Watanabe<\/span><\/a>, professor of cell biology at Johns Hopkins University. The study, posted on bioRxiv in July,\u00a0suggests microglia might be recruited to get rid of this buildup.<\/span>\r\n\r\nAfter observing microglia take up organelle aggregations from neurons in a cell culture, the researchers began looking for the same thing in a live brain, Watanabe says. Outside healthy brains, microglia have an \u201camoeba-like\u201d appearance and behave differently, he says. \u201cWe cannot publish anything without in-vivo imaging in microglia.\u201d<\/span>\r\n\r\nThis work involved years of trial and error, because \u201cyou're kind of imaging blindly,\u201d says study investigator <\/span>Renee Pepper<\/span><\/a>, a postdoctoral researcher in Watanabe\u2019s lab.\u00a0<\/span>\r\n\r\n[tt_text class='']I[\/tt_text]n the somatosensory cortex, microglia extended processes toward an average of 77 percent of the observed stationary organelles during 15-minute two-photon imaging sessions. Over several minutes,\u00a0 processes would \u201ctouch the organelle and pull back, and then go back again,\u201d Pepper says, and following those contacts, a fluorescent tag on the neurons\u2019 proteolytic organelles moved to the microglia.<\/span>\r\n\r\nThese interactions, which the researchers call skoupocytosis, are most common in the axon and appear to be distinct from previously documented instances of microglia nibbling synapses.<\/span>\r\n\r\n[tt_sidebar_quote author='Renee Pepper<\/span>']This work involved years of trial and error, because \u201cyou\u2019re kind of imaging blindly.<\/span>[\/tt_sidebar_quote]\r\n\r\nThe protein makeup of synaptic terminals from artificially stimulated neuronal cultures revealed high levels of an enzyme called alpha\/beta hydrolase domain-containing (ABHD16A). It <\/span>regulates the amount<\/span><\/a> of an extracellular form of phosphatidylserine (PS), a signaling molecule involved in<\/span> microglial synaptic pruning<\/span><\/a>. Blocking the enzyme reduces the proportion of PS outside the cell and increases the size of organelles accumulating in neurons, the new study shows.<\/span>\r\n\r\nThis suggests that PS, once released outside the cell, could act as a flare for microglia to perform skoupocytosis, and that microglia don\u2019t indiscriminately engulf bits of neurons but know precisely what to take, says <\/span>Nicole Scott-Hewitt<\/span><\/a>, assistant professor in the cell biology department at Duke University, who was not involved in the study. The new study, Scott-Hewitt says, adds to our understanding of the language of molecules that neurons and microglia use to communicate with each other.\u00a0<\/span>\r\n\r\nAlthough the findings hint at a mechanism, the details have yet to be worked out, and there are likely more molecules involved, Watanabe says. How microglia interpret neuronal distress signs correctly is what he would like to look into next, he says.<\/span>\r\n\r\nA strength of the study is combining in-vivo, in-vitro and in-situ approaches, along with imaging techniques, says <\/span>Marie-\u00c8ve Tremblay<\/span><\/a>, professor of medical sciences at the University of Victoria, who was not involved in the study.\u00a0<\/span>\r\n\r\nObserving microglia in the healthy brain is especially tricky, Tremblay says, because they \u201crapidly transform on a timescale of seconds and minutes, and can become toxic when taken out of their brain environment.\u201d The new study expands on the past two decades of in-vivo work in showing that microglia are \u201cextremely dynamic in the healthy brain,\u201d she says.\u00a0\u00a0<\/span>\r\n\r\nSkoupocytosis might be rare in healthy brains, however, because the proteolytic organelles produced in healthy states are typically small enough to squeeze through the axon, Nixon says. Although the researchers found skoupocytosis in vivo without manipulating neuronal activity, the only way to reliably get the organelles to accumulate for in-vitro experiments was by artificially inducing activity, Pepper says. She plans to look at how synaptic activity recruits the molecular players involved in skoupocytosis and how important it is for synapse function.<\/span>\r\n\r\n\u201cSeeing two things that are different, like interacting in a coordinated\u201d way stimulates an \u201cinnate biological curiosity,\u201d says <\/span>Fernando Gonz\u00e1lez Ib\u00e1\u00f1ez<\/span><\/a>, who was not involved in the study and who asked to be identified as a Mexican postdoctoral researcher in Tremblay\u2019s lab. \u201cTaking something out without this cell bursting,\u201d is a tricky process involving a host of mechanical forces, he adds. <\/span>"}]},"_links":{"self":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256656","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/users\/73"}],"replies":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/comments?post=256656"}],"version-history":[{"count":7,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256656\/revisions"}],"predecessor-version":[{"id":256681,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256656\/revisions\/256681"}],"acf:post":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/contributor\/235277"}],"acf:term":[{"embeddable":true,"taxonomy":"post_tag","href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/tags\/34"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/media\/256664"}],"wp:attachment":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/media?parent=256656"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/categories?post=256656"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/tags?post=256656"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}},{"id":256614,"date":"2026-09-23T00:00:13","date_gmt":"2026-09-23T04:00:13","guid":{"rendered":"https:\/\/www.thetransmitter.org\/?p=256614"},"modified":"2026-09-22T16:02:07","modified_gmt":"2026-09-22T20:02:07","slug":"how-neuromorphic-computing-could-improve-ai","status":"publish","type":"post","link":"https:\/\/www.thetransmitter.org\/theoretical-neuroscience-podcast\/how-neuromorphic-computing-could-improve-ai\/","title":{"rendered":"How neuromorphic computing could improve AI"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"

Mihai Petrovici explains what neuromorphic computing is and how it can speed up and reduce energy consumption in artificial intelligence and brain simulations.<\/p>\n","protected":false},"author":78,"featured_media":256615,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","footnotes":""},"categories":[156],"tags":[143,148,309,1216,25,1208],"class_list":["post-256614","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-podcasts","tag-computational-neuroscience","tag-methods","tag-neural-dynamics","tag-neuromorphic-computing","tag-technology","tag-theoretical-neuroscience-podcast"],"acf":{"primary_tag":1208,"doi_url":"","citation_count":"","custom_js_library":"","hero_type":"youtube","hero_alt_image":null,"hero_youtube":"anJgf0dEbgg","hero_video":null,"hero_layout":"landscape","hero_caption":"","hero_by":"","hero_credit":"","hero_bg_color":"tan","authors":[221738],"other_authors":"","related_title":"Explore more from The Transmitter<\/em>","related_hide":false,"related_filter":"latest","related_tag":null,"related_category":null,"related_custom":{"articles":null},"related_custom_wwn":{"articles":null},"newsletter":"","banner_content":"","banner_url":"","apple_article_id":"6e42dc6d-9c2d-4f93-bed5-d8083173320c","apple_article_revision":"AAAAAAAAAAD\/\/\/\/\/\/\/\/\/\/w==","google_button_text":"","google_btn_bg_color":"","tooltip_text":"","sidebar_related_hide":false,"sidebar_related_title":"related articles","sidebar_related_hide_images":false,"sidebar_related_articles":"","comps":[{"acf_fc_layout":"audio_comp","audio_title":"","audio":256617,"apple_link":"","spotify_link":"","google_link":""},{"acf_fc_layout":"copy_comp","copy":"In this episode of the \u201cTheoretical Neuroscience\u201d podcast, Gaute Einevoll talks with <\/span>Mihai Petrovici<\/span><\/a>, senior researcher at the University of Bern. His group develops brain-inspired computing systems that use neuromorphic hardware to emulate neural dynamics efficiently and to investigate how networks of spiking neurons can perform computation.<\/span>\r\n\r\nRead the transcript<\/a>."}]},"_links":{"self":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256614","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/users\/78"}],"replies":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/comments?post=256614"}],"version-history":[{"count":4,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256614\/revisions"}],"predecessor-version":[{"id":256683,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256614\/revisions\/256683"}],"acf:post":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/contributor\/221738"}],"acf:term":[{"embeddable":true,"taxonomy":"post_tag","href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/tags\/1208"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/media\/256615"}],"wp:attachment":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/media?parent=256614"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/categories?post=256614"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/tags?post=256614"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}},{"id":256594,"date":"2026-09-22T00:00:50","date_gmt":"2026-09-22T04:00:50","guid":{"rendered":"https:\/\/www.thetransmitter.org\/?p=256594"},"modified":"2026-09-22T11:42:36","modified_gmt":"2026-09-22T15:42:36","slug":"hasty-stem-cells-highlight-potential-limitation-with-cortical-organoids","status":"publish","type":"post","link":"https:\/\/www.thetransmitter.org\/neurodevelopment\/hasty-stem-cells-highlight-potential-limitation-with-cortical-organoids\/","title":{"rendered":"Hasty stem cells highlight potential limitation with cortical organoids"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"

The models recapitulate many key developmental processes, but some radial glial cells in mouse organoids make neurons earlier than they should.<\/p>\n","protected":false},"author":73,"featured_media":256596,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","footnotes":""},"categories":[152],"tags":[29,104,157,109,301,39,41],"class_list":["post-256594","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","tag-cortex","tag-glial-cells","tag-neurodevelopment","tag-neurogenesis","tag-neurons","tag-organoids","tag-stem-cells"],"acf":{"primary_tag":157,"doi_url":"https:\/\/doi.org\/10.53053\/LRMS1498","citation_count":"0","custom_js_library":"","hero_type":"feat_image","hero_alt_image":null,"hero_youtube":"","hero_video":null,"hero_layout":"landscape","hero_caption":"Cell families:<\/strong> Neurons and progenitor cells in a mouse cortical organoid are labeled in green, red and yellow, with cell nuclei shown in blue.","hero_by":"","hero_credit":"","hero_bg_color":"tan","authors":[107386],"other_authors":"","related_title":"Explore more from The Transmitter<\/em>","related_hide":false,"related_filter":"latest","related_tag":null,"related_category":null,"related_custom":{"articles":null},"related_custom_wwn":{"articles":null},"newsletter":"","banner_content":"","banner_url":"","apple_article_id":"909b0fac-2704-45e6-b2a2-10f18388306b","apple_article_revision":"AAAAAAAAAAAAAAAAAAAAAA==","google_button_text":"","google_btn_bg_color":"","tooltip_text":"","sidebar_related_hide":false,"sidebar_related_title":"related articles","sidebar_related_hide_images":false,"sidebar_related_articles":"","comps":[{"acf_fc_layout":"copy_comp","copy":"Neural stem cells in mouse cortical organoids generate many of the same cell types as those in the developing brain, but individual stem-cell lineages do not follow the orderly developmental progression seen in vivo, according to a new <\/span>study<\/span><\/a>.<\/span>\r\n\r\nSo even though the organoids\u2019 self-organization can reproduce much of cortical development, it may not accurately mimic when individual neural stem cells divide or the neurons they produce, the findings suggest.<\/span>\r\n\r\n\u201cThe good news is that we show that a large part of the developmental processes\u2014the fundamental processes\u2014are remarkably similar,\u201d says study investigator <\/span>Simon Hippenmeyer<\/span><\/a>, professor at the Institute of Science and Technology Austria. The work, he says, is reassuring for researchers using organoids but also reveals some of the model\u2019s limitations.<\/span>\r\n\r\nThe findings could also have implications beyond mouse organoids, says <\/span>Flora Vaccarino<\/span><\/a>, professor of neuroscience at Yale University, who was not involved in the study. Many developmental processes are shared between mouse and human, and the study could encourage researchers to track radial glia development in human brain organoids to determine which features are conserved and which differ, she says.<\/span>\r\n\r\n[tt_text class='']R[\/tt_text]adial glial progenitors\u2014the neural stem cells that generate excitatory neurons in the cortex\u2014typically progress through a predictable sequence: Early in mouse development, they divide to expand the stem-cell population. Then they start producing neurons, followed by glial cells.<\/span>\r\n\r\nHippenmeyer and his team tracked individual radial glial progenitors over time in mouse cortical organoids\u2014recording how they divided and what types of cells they produced\u2014and then compared those lineages with ones they had <\/span>previously mapped<\/span><\/a> in the developing mouse cortex.<\/span>\r\n\r\nOverall, the organoids developed like the mouse cortex, producing similar types and proportions of cells with similar gene activity patterns at comparable stages. But some of the organoids\u2019 radial glial cells started making neurons earlier than their counterparts in vivo, while others were still expanding the stem-cell population.<\/span>\r\n\r\n[tt_sidebar_quote author='Simon Hippenmeyer<\/span>']The good news is that we show that a large part of the developmental processes\u2014the fundamental processes\u2014are remarkably similar.<\/span>[\/tt_sidebar_quote]\r\n\r\nStill, the broad sequence of radial glial cell development is preserved, with neurons being produced before glia, Hippenmeyer says. The organoid stem cells, he adds, \u201ccan read the hour, but they miss the precision at the minute scale.\u201d<\/span>\r\n\r\nThese cells also tended to produce a narrower range of neurons, the team found. In the developing brain, individual radial glial cells typically give rise to both CTIP2-positive neurons, which project outside the cortex, and SATB2-positive neurons, which connect the two brain hemispheres. In organoids, about one-third of lineages produced only one type or the other, compared with about 3 percent of lineages<\/span> in vivo. The researchers detailed their findings last month in <\/span>Nature.<\/span><\/i>\r\n\r\n[tt_text class='']T[\/tt_text]he study didn\u2019t identify the cause of the mismatch between organoids that look broadly normal and individual lineages that behave differently. Missing features of the stem-cell environment\u2014including blood vessels, microglia and interneurons\u2014could contribute, and Hippenmeyer says several factors may work together.<\/span>\r\n\r\nStill, the mismatch is important to recognize, says <\/span>Aparna Bhaduri<\/span><\/a>, associate professor of biological chemistry at the University of California, Los Angeles, who was not involved in the work. For studies that focus on specific cell lineages, researchers may need to check organoid results against other methods or real brain tissue, she says. \u201cIt\u2019s always important to know and benchmark the systems that you\u2019re using.\u201d<\/span>\r\n\r\nBecause mouse and human stem cells develop in similar ways, it is likely the same phenomenon occurs in human brain organoids, says <\/span>In-Hyun Park<\/span><\/a>, associate professor of genetics and neuroscience at Yale University, who was not involved in the study.\u00a0<\/span>\r\n\r\nThe human fetal cortex also contains a wider variety of radial glial cells, which could lead to even greater differences from development in vivo, but testing that directly is difficult because researchers can\u2019t perform the same kind of lineage tracing in the developing human cortex, Park says.<\/span>\r\n\r\nThe new findings suggest researchers should be careful not to assume that human organoids reproduce every aspect of brain development, says <\/span>Anthony Wynshaw-Boris<\/span><\/a>, professor of genetics and genome sciences at Case Western Reserve University, who was not involved with the research. But, he adds, organoids still offer a valuable way to study neurodevelopmental conditions that are difficult or impossible to investigate directly in people.<\/span>"}]},"_links":{"self":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256594","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/users\/73"}],"replies":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/comments?post=256594"}],"version-history":[{"count":9,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256594\/revisions"}],"predecessor-version":[{"id":256625,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/posts\/256594\/revisions\/256625"}],"acf:post":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/contributor\/107386"}],"acf:term":[{"embeddable":true,"taxonomy":"post_tag","href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/tags\/157"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/media\/256596"}],"wp:attachment":[{"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/media?parent=256594"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/categories?post=256594"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.thetransmitter.org\/wp-json\/wp\/v2\/tags?post=256594"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}},{"id":256554,"date":"2026-09-22T00:00:26","date_gmt":"2026-09-22T04:00:26","guid":{"rendered":"https:\/\/www.thetransmitter.org\/?p=256554"},"modified":"2026-09-22T11:46:41","modified_gmt":"2026-09-22T15:46:41","slug":"two-populations-of-neurons-two-effects-on-sociability-and-more","status":"publish","type":"post","link":"https:\/\/www.thetransmitter.org\/spectrum\/two-populations-of-neurons-two-effects-on-sociability-and-more\/","title":{"rendered":"Two populations of neurons, two effects on sociability; and more"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"

Here is a roundup of autism-related news and research spotted around the web for the week of 21 September.<\/p>\n","protected":false},"author":73,"featured_media":205458,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","footnotes":""},"categories":[152],"tags":[17,207,197,196],"class_list":["post-256554","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","tag-autism","tag-science-and-society","tag-spectrum","tag-spotted"],"acf":{"primary_tag":197,"doi_url":"https:\/\/doi.org\/10.53053\/KZBR7736","citation_count":"0","custom_js_library":"","hero_type":"alt_image","hero_alt_image":"","hero_youtube":"","hero_video":null,"hero_layout":"full","hero_caption":"","hero_by":"","hero_credit":"","hero_bg_color":"none","authors":[107484],"other_authors":"","related_title":"Explore more from The Transmitter<\/em>","related_hide":false,"related_filter":"latest","related_tag":null,"related_category":null,"related_custom":{"articles":null},"related_custom_wwn":{"articles":null},"newsletter":"","banner_content":"","banner_url":"","apple_article_id":"1867a40c-bb73-4719-9ccd-e6b2a53e9737","apple_article_revision":"AAAAAAAAAAAAAAAAAAAAAA==","google_button_text":"","google_btn_bg_color":"","tooltip_text":"","sidebar_related_hide":false,"sidebar_related_title":"related articles","sidebar_related_hide_images":false,"sidebar_related_articles":"","comps":[{"acf_fc_layout":"copy_comp","copy":"Social circuit:<\/b> Social behaviors are differentially modulated by distinct neuron types in the nucleus accumbens, according to a new <\/span>study<\/span><\/a> in a mouse model of autism. D1-dopamine receptor-containing medium spiny neurons promote sociability in mice missing the autism-linked CNTNAP2 gene, whereas D2-containing neurons suppress the behavior. Further, selectively inhibiting D2-containing neurons increased social interaction in the knockout mice, \u201cproviding proof of principle that targeted modulation of nucleus accumbens circuit activity can ameliorate social deficits,\u201d the authors write.\u00a0<\/span>\r\n\r\nAutism research spotted this week:<\/b>\r\n