# Serotonergic modulation of hippocampal function

> **NIH NIH R01** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2021 · $427,481

## Abstract

Project Summary. Most neuropsychiatric disorders have developmental origins. Such developmental
vulnerability is often restricted to sensitive periods, but affected behaviors, modulating factors, and underlying
mechanisms are scarcely understood. We have identified an early postnatal 5-HT-sensitive period in mice that
affects adult anxiety/depression-related behaviors and cognitive function. Altered adult behaviors are
associated with reduced 5-HTergic activity in this mouse model, but it remains unknown if a causal relationship
exists. In wildtype mice, it is well established that 5-HT signaling modulates anxiety and depression-related
behaviors and cognitive function. But also here, mechanistic insight at the level of 5-HTergic circuitry remains
superficial. Hence, in the context of understanding normal brain function as well as developmental vulnerability,
we view it as critical to understand the role of 5-HT input into postsynaptic circuits and its relationship with
behavior. We furthermore believe that such insight into circuit function is needed to improve diagnosis and
treatment strategies for neuropsychiatric disorders. Our proposal focuses on studying 5-HTergic input into the
hippocampus. We study the hippocampus, because it receives dense 5-HTergic innervation from raphé nuclei,
and it mediates and modulates emotional behaviors and cognitive function. Through optogenetics and in vivo
calcium-photometry, we will directly investigate the relationship between 5-HTergic neurotransmission in CA1
and spatial memory and anxiety. We focus on CA1, because it is the converging point and the output region of
the direct and indirect pathway within the hippocampus. We study the dorsal and ventral CA1 separately,
because of their hypothesized differential role in cognitive and emotional function.
 Our research will impact the understanding of the pathophysiology in depression/anxiety and cognitive
impairment. Importantly our research will likewise impact our understanding of how to treat these same
conditions. Our preliminary data suggest that increased 5-HTergic signaling during development leads to
reduced 5-HTergic neuronal activity in adulthood, which in turn causes behavioral inhibition/anxiety and
cognitive impairment. Conversely, increasing 5-HTergic activity through optogenetic means reverses at least
some cognitive impairment. These findings already indicate that the firing rate of 5-HTergic neurons might be a
promising biological target for the treatment of anxiety and depression related symptomatology. We already
identified the 5-HT receptor within the hippocampus that relays the 5-HTergic signal to the postsynaptic
circuitry to improve learning and memory. This receptor might be an interesting molecular target for drug
development. Clearly, more research is needed to increase confidence in such ideas. However, we believe
these examples provide strong evidence that the novel insight our studies will provide could in fact lead to
improved d...

## Key facts

- **NIH application ID:** 10231006
- **Project number:** 5R01MH113569-05
- **Recipient organization:** NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
- **Principal Investigator:** Mark Sascha Ansorge
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $427,481
- **Award type:** 5
- **Project period:** 2017-08-08 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10231006

## Citation

> US National Institutes of Health, RePORTER application 10231006, Serotonergic modulation of hippocampal function (5R01MH113569-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10231006. Licensed CC0.

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