{"id":50616,"date":"2025-04-25T23:18:10","date_gmt":"2025-04-25T23:18:10","guid":{"rendered":"https:\/\/www.europesays.com\/uk\/50616\/"},"modified":"2025-04-25T23:18:10","modified_gmt":"2025-04-25T23:18:10","slug":"serotonin-neurons-challenge-old-views-of-brain-function","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/uk\/50616\/","title":{"rendered":"Serotonin Neurons Challenge Old Views of Brain Function"},"content":{"rendered":"<p><strong>Summary: <\/strong>Serotonin neurons in the brainstem are not independent, as once thought, but interact to influence decision-making. Researchers found that clusters of serotonin neurons compete and collaborate, shaping when and how serotonin is released throughout the brain.<\/p>\n<p>This discovery challenges older views of a uniform serotonin signal and may have major implications for understanding mood disorders and how the brain handles binary decisions. The team identified a brain circuit involving the lateral habenula that helps compute \u201cgo\u201d or \u201cdon\u2019t go\u201d decisions in response to perceived threats.<\/p>\n<p><strong>Key Facts:<\/strong><\/p>\n<ul class=\"wp-block-list\">\n<li><strong>Serotonin Networks:<\/strong> Serotonin neurons form interconnected ensembles that regulate dynamic serotonin release.<\/li>\n<li><strong>Decision Circuits:<\/strong> A newly identified circuit links the lateral habenula to serotonin activity, guiding binary decisions.<\/li>\n<li><strong>Behavioral Impact:<\/strong> This new understanding could inform targeted therapies for mood disorders like depression.<\/li>\n<\/ul>\n<p><strong>Source: <\/strong>University of Ottawa<\/p>\n<p><strong>Our lives are filled with binary decisions \u2013 choices between one of two alternatives. But what\u2019s really happening inside our brains when we engage in this kind of decision-making?<\/strong><\/p>\n<p>A\u00a0University of Ottawa Faculty of Medicine-led study published in\u00a0Nature Neuroscience\u00a0sheds new light on these big questions, illuminating a general principle of neural processing in a mysterious region of the midbrain that is the\u00a0very origin of our central serotonin (5-HT) system, a key part of the nervous system involved in a remarkable range of cognitive and behavioral functions.<\/p>\n<p>  <img fetchpriority=\"high\" decoding=\"async\" width=\"1200\" height=\"799\" src=\"https:\/\/www.europesays.com\/uk\/wp-content\/uploads\/2025\/04\/serotonin-decision-making-neuroscience.jpg\" alt=\"This shows a brain and a person at a cross roads.\"  \/> The research team\u2019s work has implications for how our brain \u2013 an organ with profoundly intricate wiring of neurons with multitudes of enmeshed connections \u2013 is involved in day-to-day decision making. Credit: Neuroscience News<\/p>\n<p>\u201cThe current dominating model is that individual 5-HT neurons are acting independently one from another. While it had previously been suggested that 5-HT neurons may rather be connected with one another, it had not been directly demonstrated. That is what we did here.<\/p>\n<p>\u201cWe also identify an intriguing processing role \u2013 or a computation \u2013 that is supported by this particular type of connectivity between 5-HT neurons,\u201d says\u00a0Dr. Jean-Claude B\u00e9\u00efque, full professor in the\u00a0Faculty\u2019s Department of Cellular and Molecular Medicine\u00a0and co-director of the\u00a0uOttawa Brain and Mind\u00a0Research Institute\u2019s Centre for Neural Dynamics and Artificial Intelligence.<\/p>\n<p>The international research team\u2019s work involved a mixture of several experimental approaches such as electrophysiology, cellular imaging, optogenetics and behavioral approaches, along with mathematical modeling and computer simulations.<\/p>\n<p><strong>Forging advances<\/strong><\/p>\n<p>So what does it mean that serotonin neurons clustered together in the brainstem are not independent actors largely keeping to themselves but are actually\u00a0sending axons to the rest of the brain?<\/p>\n<p>\u201cIn my view, the paper\u2019s main takeaway is that the mammalian serotonin system is far more anatomically and functionally complex than what we previously imagined.<\/p>\n<p>\u201cThis is knowledge that could potentially help develop targeted therapeutics for mood disorders like major depressive disorder,\u201d says Dr. Michael Lynn, the study\u2019s first author and a former member of Dr. B\u00e9\u00efque\u2019s Faculty of Medicine lab.<\/p>\n<p>Dr. Lynn received his PhD in Neuroscience from the University of Ottawa in October 2023. He\u2019s now working as a postdoctoral fellow at the\u00a0University of Oxford, in the Department of Physiology, Anatomy and Genetics.<\/p>\n<p>He says the team\u2019s findings are important because it turns out that there are distinct groups of serotonin neurons with their own activity patterns, each controlling serotonin release in a particular region of the brain.<\/p>\n<p>This has implications for the \u201cwinner-takes-all\u201d principle of neuroscience \u2013 an idea applied in computational models of neural networks in which neurons essentially compete to get activated.<\/p>\n<p>\u201cThe new principles uncovered in this paper suggest that these distinct ensembles can interact in some scenarios: \u2018winning\u2019 serotonin ensembles with high activity can strongly reduce serotonin release from \u2018losing\u2019 serotonin ensembles with lower activity levels,\u201d he says.<\/p>\n<p>\u201cThese imply a more complex, dynamic set of rules about how and when serotonin is released throughout the brain, contrasting with an older view of a more monolithic signal.\u201d<\/p>\n<p><strong>Decisions, decisions<\/strong><\/p>\n<p>The research team\u2019s work has implications for how our brain \u2013 an organ with profoundly intricate wiring of neurons with multitudes of enmeshed connections \u2013 is involved in day-to-day decision making.<\/p>\n<p>They determined how the lateral habenula, a region that is activated when we are frustrated and that is implicated in major depression, ultimately controls the activity of serotonin neurons.<\/p>\n<p>Habenular neurons are also believed to encode the level of threat that is perceived from a particular environment, or perhaps even from our actions.<\/p>\n<p>Dr. B\u00e9\u00efque explains it like this: \u201cDo we jump from the high diving board at the pool? Or only from the low one? Do we walk down that very dark alley, or do we avoid it? \u00a0When is dark too dark? \u00a0<\/p>\n<p>\u201cSomehow our brain must compute features of our world \u2013 including how threatening a particular environment is \u2013 and come up with a binary output: you go, or you don\u2019t.\u201d<\/p>\n<p>\u201cWe think we have identified a circuit that participates in that very computation that guides our everyday decisions,\u201d he says.<\/p>\n<p><strong>Next steps<\/strong><\/p>\n<p>What\u2019s next for the research team as they build on the advances they have forged over several years with this methodical, innovative examination of the serotonin system? They aim to focus on behavioral studies with mouse models.<\/p>\n<p>\u201cAt this point, the behavioral manifestations of the computation we discovered were somewhat artificial behavior. We\u2019re currently trying to see if we can see similar things when mice are behaving in more naturalistic environments,\u201d Dr. B\u00e9\u00efque says.<\/p>\n<p>The talent-rich research team for the new\u00a0Nature Neuroscience\u00a0paper included the\u00a0uOttawa Faculty of Medicine\u2019s\u00a0Dr. Richard Naud,\u00a0a computational neuroscientist who was the senior author on a recent serotonin-related study published in\u00a0Nature, and Sean Geddes, director of Innovation and Partnerships at Ottawa.<\/p>\n<p>About this serotonin and decision-making research news<\/p>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Author: <\/strong><a href=\"http:\/\/neurosciencenews.com\/cdn-cgi\/l\/email-protection#a2d2cecdc5cdd6cac7e2d7cdd6d6c3d5c38cc1c3\" target=\"_blank\" rel=\"noreferrer noopener\">Paul Logothetis<\/a><br \/><strong>Source: <\/strong><a href=\"https:\/\/uottawa.ca\" target=\"_blank\" rel=\"noreferrer noopener\">University of Ottawa<\/a><br \/><strong>Contact: <\/strong>Paul Logothetis \u2013 University of Ottawa<br \/><strong>Image: <\/strong>The image is credited to Neuroscience News<\/p>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Original Research: <\/strong>Open access.<br \/>\u201c<a href=\"https:\/\/dx.doi.org\/10.1038\/s41593-025-01912-7\" target=\"_blank\" rel=\"noreferrer noopener\">Nonlinear recurrent inhibition through facilitating serotonin release in the raphe<\/a>\u201d by Jean-Claude B\u00e9\u00efque et al. Nature Neuroscience<\/p>\n<p><strong>Abstract<\/strong><\/p>\n<p><strong>Nonlinear recurrent inhibition through facilitating serotonin release in the raphe<\/strong><\/p>\n<p>Serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) receive a constellation of long-range inputs, yet guiding principles of local circuit organization and underlying computations in this nucleus are largely unknown.<\/p>\n<p>Using inputs from the lateral habenula to interrogate the processing features of the mouse DRN, we uncovered 5-HT1A receptor-mediated recurrent connections between 5-HT neurons, refuting classical theories of autoinhibition.<\/p>\n<p>Cellular electrophysiology and imaging of a genetically encoded 5-HT sensor revealed that these recurrent inhibitory connections spanned the raphe, were slow, stochastic, strongly facilitating and gated spike output.<\/p>\n<p>These features collectively conveyed highly nonlinear dynamics to this network, generating excitation-driven inhibition and winner-take-all computations.<\/p>\n<p>In vivo optogenetic activation of lateral habenula inputs to DRN, at frequencies where these computations are predicted to ignite, transiently disrupted expression of a reward-conditioned response in an auditory conditioning task.<\/p>\n<p> Together, these data identify a core computation supported by an unsuspected slow serotonergic recurrent inhibitory network.<\/p>\n","protected":false},"excerpt":{"rendered":"Summary: Serotonin neurons in the brainstem are not independent, as once thought, but interact to influence decision-making. Researchers&hellip;\n","protected":false},"author":2,"featured_media":50617,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11],"tags":[215,27181,105,219,220,376,16,15,1916],"class_list":{"0":"post-50616","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-health","8":"tag-brain-research","9":"tag-decision-making","10":"tag-health","11":"tag-neurobiology","12":"tag-neuroscience","13":"tag-serotonin","14":"tag-uk","15":"tag-united-kingdom","16":"tag-university-of-ottawa"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@uk\/114401162275182063","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/50616","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/comments?post=50616"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/50616\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media\/50617"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media?parent=50616"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/categories?post=50616"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/tags?post=50616"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}