# Cholinergic Modulation of VIP Neurons in the Auditory Midbrain and its Impact on the Excitability of Thalamic Neurons

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $40,014

## Abstract

Abstract
How our brains identify and respond to speech and other auditory cues remains unclear. Neurons in the inferior
colliculus (IC), a hub for auditory processing located in the midbrain, exhibit selective responses to the spectral
and temporal features of speech and other complex sounds. Previous findings suggest that acetylcholine (ACh),
a neuromodulator associated with attention and synaptic plasticity, may provide an attention-based mechanism
to alter auditory processing in the IC. Furthermore, neurons in the IC express different combinations of nicotinic
acetylcholine receptor (nAChR) subunits. However, the cellular mechanisms underlying cholinergic modulation
in the IC and its impact on downstream targets in the auditory thalamus remain unknown. We recently found that
brief pulses of ACh drive prolonged periods of firing in Vasoactive Intestinal Peptide (VIP) neurons in the IC.
Moreover, VIP neurons project to the auditory thalamus (medial geniculate, MG), and we obtained preliminary
data suggesting that brief pulses of VIP promote strong depolarization in a subset of MG neurons. We
hypothesize that ACh enhances excitability of VIP neurons through a nAChR-dependent signaling pathway and
that VIP neurons in turn use glutamatergic and VIP signaling to drive prolonged excitability of postsynaptic
neurons in the MG. To address this, we are using brain slice electrophysiology and pharmacology to determine
the mechanisms that govern the modulatory effects of ACh on VIP neurons and VIP on MG neurons. Our
preliminary results show that the prolonged firing of VIP neurons elicited by brief pulses of ACh depends on
activation of α4β2 nAChRs. Furthermore, we found that this effect is not abolished by blocking glutamatergic,
GABAergic, and glycinergic synaptic transmission or by reducing extracellular Ca2+, suggesting that ACh acts by
activating α4β2 nAChRs expressed on VIP neurons themselves and not through activation of neurons presynaptic
to VIP neurons. Additionally, our preliminary data show that brief pulses of VIP elicit prolonged depolarization in
MG neurons. The overall objective of this proposal is to determine for the first time how cholinergic modulation
alters activity in an identified class of IC principal neurons and how these alterations in turn affect activity in the
MG. In Aim 1, we will combine brain slice electrophysiology with pharmacology and optogenetics to determine
the receptors and mechanisms involved in cholinergic modulation of IC VIP neurons. In Aim 2, we will use brain
slice electrophysiology, pharmacology and channelrhodopsin-assisted circuit mapping (CRACM) to determine
how synaptic transmission from VIP neurons affects the excitability of MG neurons. Overall, our results will
provide a mechanistic basis for how cholinergic modulation in the IC shapes neuron excitability in the IC and MG
and will provide a foundation for determining how cholinergic modulation can be used to promote adaptive
plasticity in people with h...

## Key facts

- **NIH application ID:** 10472009
- **Project number:** 5F31DC019292-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Luis Miguel Rivera-Perez
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $40,014
- **Award type:** 5
- **Project period:** 2020-09-04 → 2023-09-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10472009

## Citation

> US National Institutes of Health, RePORTER application 10472009, Cholinergic Modulation of VIP Neurons in the Auditory Midbrain and its Impact on the Excitability of Thalamic Neurons (5F31DC019292-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10472009. Licensed CC0.

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