NIH grant: FOXP2 regulation of glutamatergic neuron subtypes in the inferior colliculus (1R56DC023104-01A1)

retained text

NIH grant 1R56DC023104-01A1: FOXP2 regulation of glutamatergic neuron subtypes in the inferior colliculus
Institute: {'code': 'DC', 'abbreviation': 'NIDCD', 'name': 'National Institute on Deafness and Other Communication Disorders', 'admin_org_id': '12500019', 'admin_funding_url': ''}. PI: Jay Robert Gibson. Award: $284532.
Start: 2026-08-07T00:00:00.
Project Summary/Abstract
The inferior colliculus (IC) is a crucial auditory processing center in the brain, yet the molecular characterizations
of its cell types are not well understood. FOXP2, a transcription factor in the FOXP family, is abundantly
expressed in the IC, although its function in the IC is completely unknown. FOXP2 is expressed primarily in
glutamatergic neurons of the IC, indicating a potential role in neuronal function for these cell types. FOXP2
mutations are associated with autism, attention-deficit/hyperactivity disorder, and speech and language deficits,
but the cellular mechanisms and transcriptional targets regulated by FOXP2 remain elusive. The IC serves as
an excellent model region to study FOXP2 due to its well-characterized sensory responses and the availability
of easily measured electrophysiological properties and reflexive behaviors. However, this approach is limited by
the lack of detailed knowledge about IC cell subtypes and FOXP2 expression in these cells. Our preliminary data
using a mouse model of Foxp2 deletion in the IC reveal two findings: 1) altered auditory-motor gating, mirrored
in systems-level physiological measurements, reflecting changes in the temporal properties of IC pathways, and
2) single-cell transcriptome analysis that provides the first unbiased categorization of IC cell types together with
the identification of the loss of specific glutamatergic subtypes in the absence of FOXP2. We hypothesize that
FOXP2 orchestrates transcriptional signaling cascades in a cell type-specific manner, essential for the
function of circuits governing auditory-motor gating and perception. We will explore the cell type-specific
contributions in the IC using a Foxp2 conditional knockout mouse with three Aims: 1) Determine the
transcriptionally defined cell subtypes in the postnatal IC and their gene expression programs regulated by
FOXP2; 2) Investigate the role of FOXP2 in the fate determination, survival, morphology and relative proportion
of distinct ICC glutamatergic neurons and the overall anatomy of the IC; and 3) Determine the role of FOXP2 in
the electrophysiological properties of glutamatergic neurons in the ICC. These aims will elucidate the cell-type-
specific roles of FOXP2 in the IC and highlight the contribution of dysfunctional FOXP2 in brain disorders.

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