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National Institutes of Health

Reissue of PAR-20-118. This Notice of Funding Opportunity (NOFO) encourages applications to advance the discovery, preclinical development, and proof of concept (PoC) testing of new, rationally based candidate agents and neurostimulation approaches to treat mental disorders, substance use disorders (SUDs) or alcohol use disorder (AUD), and to develop novel ligands and circuit-engagement devices as tools to further characterize existing or to validate new drug/device targets. Partnerships between academia and industry are strongly encouraged. This NOFO using the U01 mechanism supports a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies Projects seeking support for a research program of multiple projects directed toward a specific major objective, basic theme or program goal, requiring a broadly based, multidisciplinary and often long-term approach should consider the companion U19 FOA.

National Institutes of Health

Reissue of PAR-20-118. This Notice of Funding Opportunity (NOFO) encourages applications to advance the discovery, preclinical development, and proof of concept (PoC) testing of new, rationally based candidate agents and neurostimulation approaches to treat mental disorders, substance use disorders (SUDs) or alcohol use disorder (AUD), and to develop novel ligands and circuit-engagement devices as tools to further characterize existing or to validate new drug/device targets. Partnerships between academia and industry are strongly encouraged. This NOFO using the U01 mechanism supports a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies Projects seeking support for a research program of multiple projects directed toward a specific major objective, basic theme or program goal, requiring a broadly based, multidisciplinary and often long-term approach should consider the companion U19 FOA.

National Institutes of Health

National Cooperative Drug/Device Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders (U01 Clinical Trial Optional)

National Institutes of Health

Reissue of PAR-20-119. This FOA encourages applications to advance the discovery, preclinical development, and proof of concept (PoC) testing of new, rationally based candidate agents and neurostimulation approaches to treat mental disorders, substance use disorders (SUDs) or alcohol use disorder (AUD), and to develop novel ligands and circuit-engagement devices as tools to further characterize existing or to validate new drug/device targets. Partnerships between academia and industry are strongly encouraged. This FOA supports a research program of multiple projects directed toward a specific major objective, basic theme or program goal, requiring a broadly based, multidisciplinary and often long-term approach. Projects seeking support for a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies should consider the companion U01 FOA.

National Institutes of Health

Reissue of PAR-20-119. This FOA encourages applications to advance the discovery, preclinical development, and proof of concept (PoC) testing of new, rationally based candidate agents and neurostimulation approaches to treat mental disorders, substance use disorders (SUDs) or alcohol use disorder (AUD), and to develop novel ligands and circuit-engagement devices as tools to further characterize existing or to validate new drug/device targets. Partnerships between academia and industry are strongly encouraged. This FOA supports a research program of multiple projects directed toward a specific major objective, basic theme or program goal, requiring a broadly based, multidisciplinary and often long-term approach. Projects seeking support for a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies should consider the companion U01 FOA.

National Institutes of Health

National Cooperative Drug/Device Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders (U19 Clinical Trial Optional)

Administration for Children and Families - OFVPS

<p style="margin-left:5.25pt;">The Resource Centers support efforts to prevent and respond to family, domestic, and dating violence by providing information, training, and technical assistance to individuals, organizations, government agencies, and communities.</p><p style="margin-left:5.25pt;">The National Resource Centers on Domestic Violence focus on strengthening services and knowledge in the field. One center provides training and technical assistance on domestic violence programs, research, and services for victims and their children. Another maintains a national resource library to collect, analyze, and share information on domestic violence, prevention strategies, and services for adult and youth victims.</p><p style="margin-left:5.25pt;">The National Indian Resource Center works with tribes and tribal organizations to improve responses to domestic violence and increase safety for Indian women. It also coordinates with federal partners that serve Native communities.</p><p style="margin-left:5.25pt;">Special Issue Resource Centers address key systems that impact victims of domestic violence. These centers provide training and technical assistance on responses within the justice system, child protective services, health care, and mental health systems. Additional centers focus on improving services and prevention efforts for racial and ethnic minority communities.</p><p style="margin-left:5.25pt;">Native-focused resource centers, including those serving Native Hawaiian and Alaska Native communities, build capacity among tribes, organizations, and service providers. They coordinate with the National Indian Resource Center and deliver culturally relevant prevention and education efforts.</p><p style="margin-left:5.25pt;">The National Resource Center to Expand Services for Children, Youth, and Abused Parents strengthens support for non-abusing parents and their children, including efforts to prevent or reduce foster care involvement.</p><p style="margin-left:5.25pt;">Sexual Assault Technical Assistance Centers support grantees in improving sexual assault prevention and response through specialized expertise and training.</p>

Administration for Children and Families - OFVPS

The Resource Centers support efforts to prevent and respond to family, domestic, and dating violence by providing information, training, and technical assistance to individuals, organizations, government agencies, and communities.The National Resource Centers on Domestic Violence focus on strengthening services and knowledge in the field. One center provides training and technical assistance on domestic violence programs, research, and services for victims and their children. Another maintains a national resource library to collect, analyze, and share information on domestic violence, prevention strategies, and services for adult and youth victims.The National Indian Resource Center works with tribes and tribal organizations to improve responses to domestic violence and increase safety for Indian women. It also coordinates with federal partners that serve Native communities.Special Issue Resource Centers address key systems that impact victims of domestic violence. These centers provide training and technical assistance on responses within the justice system, child protective services, health care, and mental health systems. Additional centers focus on improving services and prevention efforts for racial and ethnic minority communities.Native-focused resource centers, including those serving Native Hawaiian and Alaska Native communities, build capacity among tribes, organizations, and service providers. They coordinate with the National Indian Resource Center and deliver culturally relevant prevention and education efforts.The National Resource Center to Expand Services for Children, Youth, and Abused Parents strengthens support for non-abusing parents and their children, including efforts to prevent or reduce foster care involvement.Sexual Assault Technical Assistance Centers support grantees in improving sexual assault prevention and response through specialized expertise and training.

NIMH - National Institute of Mental Health

PROJECT SUMMARY P HIV Pre-Exposure Prophylaxis (PrEP)harmacist autonomous-prescribing of is an HIV prevention strategy that is rapidly rising in the US – the number of states with pharmacist-prescribed PrEP has over quintupled in the past five years andPrEP prescribing by pharmacists increased doubled within four years of the first state policy. Yet, studies of this HIV prevention strategy have been concentrated in a few cities and the impact of these policies have not been evaluated. Thus, we lack rigorous national data about when, where or to whom pharmacists are prescribing PrEP, whether it is happening in areas where PrEP is most needed, or the public health impact it might be having on PrEP adherence, persistence, or subsequent HIV rates. This study’s primary purpose is to evaluate, on a national level, where pharmacist-prescribed HIV PrEP is happening or not happening within states that allow it, who it reaches, and what population-level impacts it is having on HIV. Our team was the first to identify a novel population-based surveillance metric of PrEP adherence using national pharmacy claims data, finding that nearly 1 in 5 patients with an insurance-approved, new, oral PrEP script who did not pick up PrEP from their pharmacy, of which, over 70% still did not pick up PrEP within 365 days, conferring up to 5 times higher HIV risk than those who picked up PrEP consistently. We then assessed non-adherence for by the specialty of prescribing provider, but we could not assess pharmacists as a group of providers, as legislation for pharmacist-prescribed PrEP was too new for that earlier 2019 data capture. We now embark on a timely investigation of pharmacist-prescribed PrEP, to better understand where it is happening or not happening, what populations are best reached by pharmacists, and HIV rates of patients prescribed PrEP by pharmacists compared with other prescribers. We use a nationally representative claims dataset (IQVIA) that captures ~85% of all PrEP prescriptions in the US, including public, private and individual payers, along with patient demographics and National Provider Identifier, linked to prescriber data from the National Plan and Provider Enumeration System to: compare trends and timing of pharmacist-prescribed PrEP to other prescribers, mapping to where PrEP need is high (i.e., high HIV incidence) but allowed pharmacist- prescribing is not happening (Aim 1); identify the profile of patients most reached by pharmacist-prescribed PrEP (Aim 2); and compare PrEP adherence, persistence, and HIV incidence at one year, among those prescribed by pharmacists versus other prescribers (Aim 3) as an indicator of whether patients remain engaged in PrEP care after initiation at pharmacies. Our team includes expertise in epidemiology, pharmacy, biostatistics, GIS, and HIV prevention. The study has policy implications for how pharmacists are engaged in care, and where care needs to be expanded based on populations being underserved, with the expected outcome of fully integrating pharmacists into HIV prevention.

National Institutes of Health

The purpose of this NOFO is to build research about the effectiveness, implementation, and optimization of family navigation ED diversion models for non-urgent mental health problems. Models of interest are designed to (a) utilize triage tools to identify mental health acuity, (b) facilitate engagement in mental health services and needed resources, and (c) provide support, knowledge about the mental health condition, and facilitate linkages/address barriers to help-seeking among families.

National Institutes of Health

Navigator Emergency Department Diversion Models for Non-Urgent Mental Health Concerns (R01 Clinical Trial Required)

National Institutes of Health

The purpose of this NOFO is to build research about the effectiveness, implementation, and optimization of family navigation ED diversion models for non-urgent mental health problems. Models of interest are designed to (a) utilize triage tools to identify mental health acuity, (b) facilitate engagement in mental health services and needed resources, and (c) provide support, knowledge about the mental health condition, and facilitate linkages/address barriers to help-seeking among families.

National Institutes of Health

The purpose of this NOFO is to build research about the effectiveness, implementation, and optimization of family navigation ED diversion models for non-urgent mental health problems. Models of interest are designed to (a) utilize triage tools to identify mental health acuity, (b) facilitate engagement in mental health services and needed resources, and (c) provide support, knowledge about the mental health condition, and facilitate linkages/address barriers to help-seeking among families.

National Institutes of Health

Navigator Emergency Department Diversion Models for Non-Urgent Mental Health Concerns (R34 Clinical Trial Required)

National Institutes of Health

The purpose of this NOFO is to build research about the effectiveness, implementation, and optimization of family navigation ED diversion models for non-urgent mental health problems. Models of interest are designed to (a) utilize triage tools to identify mental health acuity, (b) facilitate engagement in mental health services and needed resources, and (c) provide support, knowledge about the mental health condition, and facilitate linkages/address barriers to help-seeking among families.

NC Department of Health and Human Services

NCDHHS funds nonprofits, health organizations, and community agencies providing mental health, substance abuse, developmental disability, public health, and social services to vulnerable North Carolinians.

NC Dept of Military & Veterans Affairs

Grants for veteran employment programs, housing assistance, and mental health services.

NIEHS - National Institute of Environmental Health Sciences

PROJECT SUMMARY/ABSTRACT Chronic kidney disease (CKD) and hypertension (HTN) are substantial public health concerns in the US and are important risk factors for other adverse outcomes including acute kidney injury and premature mortality. CKD and HTN are typically diagnosed later in life, yet our understanding of the prenatal and early life environ- mental determinants of reduced kidney function and HTN across childhood and early adulthood remains incipi- ent. This research, however, faces several barriers including lack of assessment of both neighborhood- and individual-level environmental stressors at specific early life stages coupled with long-term follow-up from birth to early adulthood. This project will address these research gaps by leveraging high-quality data from Project Viva, an ongoing longitudinal prospective pre-birth cohort of mother-child pairs followed since pregnancy. The overall goals of the proposed project are to examine the extent to which early-life exposure to disadvantaged neighborhood contexts and nephrotoxicants (i.e., air pollutants and metals) leads to later life kidney dysfunc- tion and higher blood pressure (BP). The investigators will: (Aim 1) examine associations of early-life neighbor- hood environment with kidney function and BP across childhood and early adulthood; (Aim 2) assess associa- tions of individual-level early-life exposure to candidate nephrotoxicants with kidney function and BP from mid- childhood to early adulthood; and (Aim 3) characterize urinary proteomic signatures underlying altered kidney function and BP trajectory from childhood to early adulthood, and examine these signatures as potential mark- ers of toxicant exposure. This innovative proposal will be the first to examine both neighborhood- and individ- ual-level environmental determinants of kidney function and BP trajectories. We will identify actionable risk fac- tors and molecular signatures to identify high-risk individuals and pinpoint when primordial prevention efforts have the greatest potential to prevent future CKD and HTN.

NIA - National Institute on Aging

ABSTRACT Menopause is a major neuroendocrine transition experienced by nearly two million individuals in the United States each year. It is associated with increased rates of depression, social withdrawal, and loss of sexual motivation, posing significant challenges to mental health, interpersonal relationships, and public health. While hormonal decline has been implicated, the neural circuit mechanisms underlying these behavioral symptoms remain poorly understood. This proposal seeks to define how hormonal decline during reproductive aging disrupts a specific hormone-sensitive neural circuit and impairs female sexual behavior. Our work focuses on a projection from Cckar-expressing neurons in the ventromedial hypothalamus (VMHvlCckar) to the anteroventral periventricular nucleus (AVPV), a pathway that is essential for female sexual behavior and highly sensitive to ovarian hormones. Using a physiologically relevant menopause model induced by 4-vinylcyclohexene diepoxide (VCD), which gradually depletes ovarian follicles without surgery, we will determine how hormonal decline alters both the structural connectivity and functional activity of this projection. Specific Aim 1 will test whether structural atrophy of the VMHvlCckar to AVPV projection occurs with hormonal decline and whether it is reversible by hormone supplementation. Specific Aim 2 will examine how hormonal decline affects activity along this circuit, revealing where circuit dysfunction arises. Specific Aim 3 will use optogenetics to test whether activating this pathway restores sexual behavior and whether AVPV activity is necessary for hormone-induced behavioral rescue. By linking hormone-sensitive circuit remodeling to behavioral impairments, this study will identify new neurobiological targets for intervention. The findings may guide the development of circuit-based therapies to support mental health and social functioning during aging.

NIMH - National Institute of Mental Health

Project Summary Biological accounts of reinforcement learning posit that dopamine encodes reward prediction errors (RPEs), which are multiplied by a learning rate to update state or action values. The learning rate is often assumed to be constant, but studies in humans, monkeys, rats, and mice, have found behavioral evidence for dynamic learning rates. In volatile environments, dynamic learning rates allow animals to learn faster when the world is changing, and more slowly when the world is stable. While dopamine is thought to instantiate RPEs, we recently found that dopamine release in the ventral striatum did not reflect learning rates, suggesting that dopamine-independent mechanisms determine the rate of error-driven learning. Moreover, we present strong preliminary data showing that inactivation of the orbitofrontal cortex (OFC) eliminates dynamic learning rates behaviorally, and that OFC neurons that project to the ventral striatum seem to encode the learning rate in their firing rates. In this proposal, we will determine how OFC projections to the ventral striatum dictate the rate of error-driven learning at behavioral and neural levels. This proposal will use a novel behavioral paradigm in rats, in which reward statistics vary over latent blocks of trials. We previously found strong behavioral signatures of dynamic learning rates in rats performing this task. High-throughput behavioral training will generate dozens of trained subjects for experiments in parallel, accelerating the rate of research progress. We will use optogenetics and electrophysiology to record from and manipulate OFC neurons that project to the ventral striatum, to determine if this projection pathway dictates behavioral learning rates (Aim 1). We will use electrophysiology and optogenetics to relate behavioral learning rates and activation of OFC neurons that project to the ventral striatum to trial-by-trial changes in evoked spiking in the striatum (Aim 2). We will use optical methods to measure dopamine release in the striatum and activation of OFC axon terminals, while simultaneously recording action potentials from the ventral striatum, to relate endogenous fluctuations in coincident dopamine and OFC inputs to trial-by-trial plasticity of evoked spiking (Aim 3). These experiments will test key predictions of “three-factor” plasticity rules in behaving animals. These experiments will address a major open question, which is how specific output pathways from OFC interact with downstream circuits to coordinate value-based decisions and learning. Neuromodulatory systems including dopamine are implicated in myriad neuropsychiatric disorders including schizophrenia and depression. A greater understanding of the circuit mechanisms by which they coordinate different aspects of behavior and interact holds promise for revealing novel therapeutic targets for these disorders.

NIEHS - National Institute of Environmental Health Sciences

PROJECT SUMMARY/ABSTRACT Major depressive disorder (MDD) is a leading and rising cause of disability in adolescents, a group undergoing rapid brain development and therefore uniquely vulnerable to environmental stressors that increase psychiatric risk. Chlorpyrifos, a widely used organophosphate pesticide, has been linked to neuropsychiatric symptoms in adolescents, but whether it directly induces symptoms or instead produces latent neurobiological changes that increase vulnerability to future stressors remains unclear. Most animal studies have focused on prenatal or adult exposures, leaving a critical gap in understanding how chlorpyrifos affects the adolescent brain and shapes long-term psychiatric risk. Preliminary data demonstrate subtle but consistent anhedonia-relevant behaviors following adolescent chlorpyrifos exposure; while these changes do not constitute full pathology, they suggest chlorpyrifos alters brain function in ways consistent with a latent vulnerability state—sensitizing the brain in ways that predispose the brain to exhibit MDD-relevant outcomes following subsequent stressors. Social stressors such as bullying and isolation, which are well-established contributors to adolescent-onset MDD, are also on the rise. Real-world exposures often involve multiple, co-occuring risks, underscoring the need to investigate their combined impact on the developing brain. The objective of this research is to use a translational mouse exposure model to identify MDD-relevant behavioral, immunological, and brain circuit changes following adolescent chlorpyrifos alone and in combination with social stress. I hypothesize that chlorpyrifos induces a vulnerability state, producing brain circuit and immune changes with minimal MDD- relevant behaviors, and that co-exposure with social stress leads to susceptibility, marked by the active emergence of MDD-relevant behaviors and pathology. In Aim 1, I will test whether chlorpyrifos alone induces neurophysiological and immunological changes without many behavioral effects. In Aim 2, I will assess how combined chlorpyrifos and social stress exposures influence MDD-relevant behavioral, brain circuit, and immune outcomes. This project will uncover, for the first time, how adolescent chlorpyrifos exposure changes brain-wide mechanisms relevant to MDD, both independently and in interaction with social stress. More broadly, this fellowship will provide integrated training in psychiatry, neuroscience, and environmental toxicology through individualized mentorship and guided research. The highly collaborative and interdisciplinary environment at the University of Iowa through the Iowa Neuroscience Institute and Environmental Health Science Research Center offers an ideal setting for this work. This training plan will support my development as a physician-scientist focused on how environmental exposures during sensitive developmental windows shape long-term brain health. My long-term goal is to help advance environmental health approaches within psychiatry and neuroscience to better protect child and adolescent mental health.

NIMH - National Institute of Mental Health

PROJECT SUMMARY/ABSTRACT Animals exhibit a remarkable array of flexible behaviors. Birds alternate between caching and retrieving food based on availability; rats reroute when familiar paths are blocked; humans revise strategies mid-game in chess. This ability to flexibly switch strategies or generate new solutions is central to intelligent behavior and is often impaired in neuropsychiatric disorders such as autism spectrum disorder and schizophrenia. Prior research has yielded key insights into what supports such cognitive flexibility: internal models of the world, including spatial and episodic knowledge encoded in the hippocampus (HPC) and abstract rules encoded in the prefrontal cortex (PFC). However, we still lack a mechanistic understanding of how the brain engages these models in real time to guide strategy switching and problem-solving. This proposal addresses this gap by identifying internal strategy states—latent variables computed by the brain that track the currently active policy for selecting goal-directed actions—and by dissecting the neural computations that encode, update, and drive transitions between these states. I will combine large-scale electrophysiology with closed-loop optogenetics in freely behaving rats performing strategy-switching and problem-solving tasks. I will assess behavioral and neural data by integrating two complementary theoretical frameworks: (i) reinforcement learning and Bayesian inference to formalize latent behavioral strategies and valuation processes; and (ii) dynamical systems modeling to uncover how neural population activity implements these cognitive operations. I will test the central hypothesis that the flexible control and generation of strategies arise from structured population dynamics in medial PFC (mPFC) implementing computations that: (i) direct HPC to simulate future scenarios that inform strategy switching (Aim 1); (ii) track and update strategy values to determine when to switch (Aim 2); and (iii) integrate input from the orbitofrontal cortex to select among multiple strategies and generate new solutions (Aim 3). By causally linking neural dynamics to strategy switching, selection, and generation, this work will reveal algorithmic and implementational principles of cognitive flexibility, laying the groundwork for my long-term goal: to elucidate the division of computational labor across PFC subregions and their interactions with subcortical regions (e.g., thalamus) during multi-strategy problem-solving. The K99 phase will support my transition to independence through training in multi-region, high-density electrophysiology coupled with real-time optogenetics, as well as advanced behavioral and dynamical systems modeling. I have assembled a mentorship team (Drs. Loren Frank, Joshua Berke, and Nathaniel Daw) and collaborators (Drs. Vikaas Sohal and Scott Linderman) with complementary expertise spanning experimental, technological, and theoretical domains of systems neuroscience. This award will also provide professional development in lab management, leadership, scientific communication, and grant writing, which will position me to launch an independent research program focused on the neural basis of intelligence and creative behavior.

NIMH - National Institute of Mental Health

PROJECT SUMMARY Memory is an essential cognitive process dependent on the consolidation of experience into stored memories and generalized knowledge. We know not all memories are stored, and we know memories undergo a transformation from episodic events into abstract understanding. However, the neural underpinnings of this process of memory consolidation remain unclear. The hippocampus is a brain region critical for memory formation, and the medial prefrontal cortex (mPFC) is a brain region involved in memory storage and abstracted knowledge; these regions are bidirectionally connected and are candidate brain networks for the selection of memories for consolidation and the transformation of memory traces into generalized knowledge. Further, the sleep sharp-wave ripple (SWR) is a brain oscillation known to be involved in memory consolidation during which privileged hippocampal-mPFC communication occurs. While systems consolidation theory offers predictions of how the hippocampus and mPFC interact during SWRs to consolidate memories, these predictions have so far been difficult to causally test in the absence of multi-site neural recordings with optogenetic manipulations. To test the hypothesis that cortical-hippocampal information flow preceding SWRs is critical for the selection of memories for consolidation, this project aims to silence mPFC activity in conjunction with simultaneous large- scale electrophysiology recording of the hippocampus. This will determine the role of the mPFC in influencing hippocampal activity during SWRs, providing a mechanism by which memory traces are selected for consolidation (Aim 1). In addition, to test the hypothesis that hippocampal-cortical information flow during SWRs is critical for the emergence of consolidated, generalized cortical representations, I will specifically inhibit mPFC activity during SWRs. This will evaluate whether mPFC activity during this brain oscillation is necessary for the transformation of memory traces and the development of neural representations of generalized knowledge (Aim 2). Completion of these aims has the potential to yield fundamental insights into the neural mechanisms of memory consolidation. This study will be carried out in the lab of research sponsor, Dr. Loren Frank, at the University of California, San Francisco (UCSF). The Frank Lab is located in the Sandler Neurosciences Center, which is home to a highly innovative and collaborative community of faculty and students pursuing neuroscience investigation. Pursuing this project will accomplish the training goals of gaining expertise in in vivo electrophysiology data acquisition, developing quantitative data analysis skills, and improving my scientific communication. The training plan under this fellowship will provide preparation for an independent career as an academic neuroscientist-neurologist with the long-term goal of revealing neural circuits underlying cognitive processes and flexible behavior. In addition to the proposed research, this preparation will be achieved via composition of scientific manuscripts, engagement with vibrant intellectual communities, and neurology-geared clinical activities.

NIMH - National Institute of Mental Health

ABSTRACT This project aims to investigate the roles of a newly identified population of neurons in the supramammillary nucleus (SuM) that are essential for threat learning and avoidance behaviors. These neurons are activated by diverse stressors and may play critical roles in threat conditioning and persistent avoidance. The specific aims of this research are to: (1) elucidate the temporal dynamics and causal roles of these neurons during threat learning, avoidance, and extinction using fiber photometry, optogenetics, and behavioral assays; (2) determine whether these neurons selectively excite neuron populations in the nucleus accumbens (NAc) to promote threat avoidance; and (3) reveal the neural types in SuM and which are recruited during threat learning and sustained avoidance using advanced molecular techniques such as Projection-TAGs, barcoded retrograde viruses, and Act-seq with single nucleus RNA sequencing. By characterizing this novel neural circuitry, the project aims to advance our understanding of active coping mechanisms and contribute to the development of new treatments for stress and anxiety-related disorders by identifying potential therapeutic targets.