# Arousal-dependent modulation of layer 5 neurons in the auditory cortex

> **NIH NIH F31** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $48,974

## Abstract

PROJECT SUMMARY
Throughout the central auditory pathway, the nervous system increasingly “colors” sensory representations
with non-sensory features, such as an animal’s arousal state. Fluctuations in arousal has been found to
influence sensory information processing and behavior. The Yerkes-Dodson law describes the relationship
between arousal and task performance as an inverted-U in that intermediate states of arousal coincide with
peak performance. While this has been shown in several auditory studies, the neural correlates of this
behavioral phenomenon are poorly understood. Correlations between pupil diameter, a well-established
biomarker of arousal state, and neural activity have been reported in the auditory system. Within the auditory
cortex (ACtx), arousal has been shown to modulate the response properties of layer (L) 2/3 cells. However, the
ACtx is composed of different subpopulations of cells that each differ with respect to their physiology, anatomy,
and projection patterns. Moreover, cells contained in deeper layers, such as L5, provide the primary means by
which the ACtx sends auditory information to major subcortical stations critical for decision-making. Layer 5
comprises two distinct projection cells types: intratelencephalic (IT) and extratelencephalic (ET) cells. The
distinct anatomy and connectivity profiles of IT and ET cells lead us to hypothesize that arousal states
differentially modulate their sensory tuning properties, which then influences behavior. Our preliminary data
suggests that L5 cells are uniquely modulated by arousal. Aim 1 will characterize the arousal-dependent
changes to L5 IT and ET cell response properties in mice passively listening to pure tones. We will
simultaneously use a combination of in vivo two-photon calcium imaging and pupillometry to track neural
activity and pupil diameters, respectively. Aim 2 will discern the optimal arousal state in an auditory
categorization task and will relate L5 IT and ET cell activity at this optimal state to an animal’s performance. As
in Aim 1, pupillometry and two-photon imaging in awake mice will be used. Through a cell-type specific
approach, this research proposal will unveil the intricate relationship between arousal, distinct L5 neural
activity, and auditory-guided behaviors.

## Key facts

- **NIH application ID:** 10995435
- **Project number:** 1F31DC021867-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Keith Kaufman
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10995435

## Citation

> US National Institutes of Health, RePORTER application 10995435, Arousal-dependent modulation of layer 5 neurons in the auditory cortex (1F31DC021867-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10995435. Licensed CC0.

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