A role for neurexins in serotonin-IPN circuitry and social behavior
About This Grant
Project Summary/Abstract Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder affecting 1 in 36 children. A dyad of impairments in social interaction and flexibility of thoughts manifests early in these individuals’ lives. The heterogeneous clinical presentation of ASD arises in part due to disturbances in serotonin (5-HT) signaling. While a standard therapeutic regimen for ASD does not currently exist, 5-HT-based medications provide variable benefit for disorder relief, highlighting the need for better elucidation of specific serotonergic circuits and mechanisms contributing to ASD behaviors. Indeed, 5-HTergic signaling is derived from a widespread network of axonal projections that influence neural activity throughout the brain. Neurexins (Nrxns) are presynaptic cell-adhesion molecules and are involved in synapse formation and regulation through trans-synaptic protein interactions with postsynaptic adhesion molecules such as neuroligins. Importantly, Nrxns are a well-accepted risk factor for ASD and schizophrenia (SCZ), and both Nrxn and 5-HT mutant mouse models display deficits in social cognitive behaviors reminiscent of ASD. However, the role of Nrxns in 5-HT synaptic transmission remains unknown. The overarching goal of this proposal is to elucidate molecular mechanisms underlying 5-HT circuit formation and identify a specific 5-HT circuit responsible for social behavior by focusing on Nrxn genes. This proposal is supported by strong preliminary data demonstrating, i) social behavior deficit in 5-HT neuron-specific Nrxn triple knockout (5-HT NrxnTKO) and 5-HT Nrxn1 KO mice, and ii) altered 5-HT projections to the interpeduncular nucleus (IPN) by whole-brain imaging of serotonin transporter (SERT)-positive fibers in 5- HT Nrxn TKO mice. As recent studies have implicated the IPN as a critical node for social behavior, our data highlight the potential significance of the 5-HT→IPN circuit in regulating social behavior under normal conditions but also in the context of ASD. Thus, in this proposal, we will address our central hypothesis that Nrxns are essential for proper serotonergic innervation in the IPN, and their expression in 5-HT neurons is required for social behavior. To test this hypothesis, we will use a multidisciplinary approach that includes whole-brain imaging (Aim 1), in vitro fast scan cyclic voltammetry (Aim 1), and in vivo photometry (Aim 2) to investigate the molecular and circuit-level mechanisms underlying social behavior. The proposed studies will shed light on the fundamental role of Nrxn-mediated 5-HT synaptic function for the appropriate development of 5-HT circuits that influence social novelty behavior. In the long term, exploring the consequences of abnormal 5-HT signaling due to impaired Nrxn regulation may reveal novel therapeutic targets to treat social deficits in ASD.
Grant Summary
A role for neurexins in serotonin-IPN circuitry and social behavior is a NIMH - National Institute of Mental Health grant providing up to $461K for university, nonprofit, healthcare org. Applications are due 2028-07-31 (open). Check eligibility and apply with FindGrants.
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Up to $461K
2028-07-31
- 1Confirm your organization is eligible for A role for neurexins in serotonin-IPN circuitry and social behavior from NIMH - National Institute of Mental Health, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIMH - National Institute of Mental Health before the deadline.
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A role for neurexins in serotonin-IPN circuitry and social behavior: Frequently Asked Questions
Who is eligible for the A role for neurexins in serotonin-IPN circuitry and social behavior?
A role for neurexins in serotonin-IPN circuitry and social behavior is offered by NIMH - National Institute of Mental Health and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the A role for neurexins in serotonin-IPN circuitry and social behavior provide?
A role for neurexins in serotonin-IPN circuitry and social behavior provides up to $461K per award from NIMH - National Institute of Mental Health. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the A role for neurexins in serotonin-IPN circuitry and social behavior deadline?
Applications for A role for neurexins in serotonin-IPN circuitry and social behavior are due 2028-07-31 (open). Because deadlines can change, verify the date with the funder, NIMH - National Institute of Mental Health, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the A role for neurexins in serotonin-IPN circuitry and social behavior?
To apply for A role for neurexins in serotonin-IPN circuitry and social behavior, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIMH - National Institute of Mental Health.