# Compartment-specific inhibition and laminar circuit dynamics in the primate prefrontal cortex.

> **NIH NIH F30** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $53,974

## Abstract

Abnormal GABAergic inhibitory neurotransmission in the prefrontal cortex (PFC) is implicated in the cognitive
and emotional disturbances present in schizophrenia and mood disorders. Two key PFC areas that exhibit
altered activity in neuropsychiatric disorders are the lateral prefrontal cortex (LPFC) and the medial prefrontal
anterior cingulate cortex (ACC), which have distinct temporal patterns of activation and roles in executive function
and cognitive control. Neurochemically diverse inhibitory interneurons (INs) mediate inhibition in the cortex and
target specific somatodendritic compartments of pyramidal (PYR) cells, differentially modulating cortical activity.
While somatic inhibition from parvalbumin INs has a well-characterized role in the pathophysiology of
schizophrenia, emerging evidence suggests that decreased dendritic inhibition and altered GABAAR
composition in the PFC are also associated with schizophrenia and mood disorders. However, the properties of
dendritic inhibition on PYR cells across diverse LPFC and ACC areas and layers, and its contribution to
oscillations has not yet been elucidated. Thus, our overall objective with this proposal is to compare the spatial
distribution, kinetics, and synaptic physiology of dendritic inhibition on PYR cell dendrites in the ACC and LPFC
of rhesus macaques, an ideal model organism for studying the primate PFC. Our central hypothesis is that
greater dendritic inhibition and slower inhibitory current kinetics are associated with slower oscillatory dynamics
in the ACC relative to the LPFC. This would reveal a cellular and subcellular mechanism by which diverse laminar
network activity emerges in the PFC and suggest points of intervention to treat altered PFC activity observed in
cognitive and psychiatric disorders. In Aim 1, we will study inhibitory postsynaptic currents in PYR cells in the
rhesus macaque ACC and LPFC via ex vivo whole-cell patch clamp recordings, along with dendritic calcium
imaging via intracellular filling with calcium indicator dye to study subcellular calcium dynamics associated with
compartment-specific inhibition. In these experiments, will study the effect of pharmacologically blocking
GABAARs containing the α5 subunit. We will additionally perform immunohistochemistry (IHC) and confocal
imaging on these electrophysiologically-characterized PYR cells to compare the subcellular distribution of IN-
labeled inhibitory appositions between areas. In Aim 2, we will compare local field potentials (LFPs) and spike-
field coupling between putative INs and LFPs across cortical layers via acute in vivo laminar recordings in the
ACC and LPFC. We will also use IHC and confocal imaging to compare the laminar distribution of IN appositions
onto PYR cells in ACC and LPFC subregions along the medio-lateral axis. We will assess relationships between
in vivo functional and tissue-based structural laminar parameters using a biophysical PYR-IN-network model and
test how dendritic-targeting...

## Key facts

- **NIH application ID:** 10903120
- **Project number:** 1F30MH136779-01
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Benjamin James Snyder
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 1
- **Project period:** 2024-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10903120

## Citation

> US National Institutes of Health, RePORTER application 10903120, Compartment-specific inhibition and laminar circuit dynamics in the primate prefrontal cortex. (1F30MH136779-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10903120. Licensed CC0.

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