# The role of cortical long-range GABAergic inhibition on emotional learning

> **NIH NIH R01** · UNIVERSITY OF TEXAS SAN ANTONIO · 2022 · $590,420

## Abstract

PROJECT SUMMARY/ABSTRACT
Proper emotional responses are characterized by the dynamic interplay of two major forces: excitation and
inhibition. A current belief is that dysfunction of inhibition, mediated by local GABAergic interneurons, leads to a
wide range of psychopathologies including phobias and anxiety disorders. A well-established principle of the
circuit organization underlying emotional learning is that inhibition is local while excitation is both local and long-
range. Specifically, a considerable amount of research on cortico-amygdala communication (coordination of
sensory input between the auditory cortex and the lateral amygdala) relies on the reductionist view that the
auditory cortex transmits only excitatory signals. However, it has long been known that long-range GABAergic
neurons are important circuits element in many brain areas, such as the spiny projection neurons in the
striatum and the Purkinje neurons in the cerebellum. Therefore, despite the fact that the existence of cortical
long-range GABAergic neurons has been proven anatomically, previous studies have primarily focused on the
local circuit organization of GABAergic interneurons, and inhibition is frequently described as being exclusively
local. A growing body of evidence from our lab and others indicates that many of these long-range GABAergic
projections arise from neurons expressing somatostatin, parvalbumin, and more recently from vasoactive
intestinal peptide. Since somatostatin neurons form synapses primarily on the distal dendrites of target neurons,
it has been suggested that this subpopulation of GABAergic cells plays a critical role modulating the plasticity of
incoming sensory inputs. Importantly, strong preliminary evidence from our labs show that somatostatin-
expressing neurons project to the lateral amygdala (CLA-Som). This proposal aims at determining the circuit
organization and behavioral relevance of CLA-Som neurons in fear learning driven by auditory signals.
Specifically, this proposal will dissect the CLA-Som microcircuits and behavior responsible for cortical amygdala
communication answering the following questions: What are the anatomical, electrophysiological, and gene
expression properties of CLA-Som neurons? What is the impact of CLA-Som neurons on the amygdala network and
which are the circuit mechanisms through which they produce inhibition? Which are the behavioral conditions that
recruit CLA-Som neurons and their role in fear learning? These questions will be investigated using retrograde and
optogenetic labeling, specific neuronal-tagging-physiological recordings, in vivo patch clamping and linear probe
recordings, calcium imaging in freely moving mice, and pathway selective chemogentic tools during actual
learning. Discoveries from this work will be significant because they will provide foundational knowledge
regarding cortical modulation of fear learning, describe a new GABAergic cortical-amygdala pathway, and
provide new therapeutic ...

## Key facts

- **NIH application ID:** 10335937
- **Project number:** 5R01MH123260-03
- **Recipient organization:** UNIVERSITY OF TEXAS SAN ANTONIO
- **Principal Investigator:** Alfonso J Apicella
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $590,420
- **Award type:** 5
- **Project period:** 2020-04-10 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10335937

## Citation

> US National Institutes of Health, RePORTER application 10335937, The role of cortical long-range GABAergic inhibition on emotional learning (5R01MH123260-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10335937. Licensed CC0.

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