# Noradrenergic modulation of emotional arousal and learning

> **NIH NIH K01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $178,610

## Abstract

Project Summary
 An animal’s level of arousal dramatically influences its ability to filter, classify and associate stimuli in the
environment with outcomes. These processes are necessary for an animal to rapidly evaluate dangers and
rewards, and the cues that predict them. The assignment of appetitive or aversive value to a stimulus has been
studied extensively and is well-understood to involve the amygdala. However, there is little known about how
arousal affects emotional learning and behavior. This problem is of critical relevance because individuals with
anxiety, addiction, depression, schizophrenia, and attention deficit disorder specifically exhibit impaired arousal
as well as disrupted emotional processing. This proposal addresses several important, outstanding questions
regarding the neural substrates of arousal, emotional learning and behavior.
 The locus coeruleus (LC) mediates arousal and has connections with the basolateral amygdala (BLA),
but it remains unknown how the LC dynamically modulates neural activity within the BLA to cause changes in
emotional learning and behavior. I intend to characterize how LC signaling shapes single-cell and ensemble
representations of emotional valence and arousal in BLA, and use this information to probe the efficacy of
potential interventions. My proposal has three aims that use state-of-the-art behavioral, molecular/genetic,
cellular imaging, and computational techniques. In Aim 1, I utilize a novel, semi-naturalistic, dual-valence
behavioral assay to study emotional learning and behavior in combination with two-photon imaging in mice to
investigate how manipulations of emotional valence and arousal modulate neural representations in BLA. In Aim
2, I combine optogenetics and imaging to manipulate neural activity in LC while simultaneously measuring the
effects on neural representations within the BLA and animal behavior. In Aim 3, I examine natural activity patterns
of the LC as an animal transitions between different arousal levels. I will then construct a closed loop behavioral
paradigm that decodes arousal levels from the LC neural activity to trigger presentations of CSs and USs to
examine whether spontaneous fluctuations in LC activity can be harnessed to reprogram the BLA and its learned
stimulus-outcome associations. Because neuromodulatory systems are well conserved, this effort will uncover
mechanisms of neuromodulation that are likely similar in other species.
 My K01 training plan benefits from a team of co-mentors and advisors with extensive, proven expertise
in computational approaches for describing neural dynamics, cutting-edge imaging, optogenetics, and brain-
machine technologies, and understanding of psychiatric conditions. Additionally, I will complete coursework to
enhance my training in contemporary perspectives on brain function, including courses on neural networks and
graphical models. I will present data to computational neuroscientists at Columbia’s Center for Theoretical...

## Key facts

- **NIH application ID:** 10041464
- **Project number:** 1K01MH123783-01
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Pia-Kelsey Tiu O'Neill
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $178,610
- **Award type:** 1
- **Project period:** 2020-07-10 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10041464

## Citation

> US National Institutes of Health, RePORTER application 10041464, Noradrenergic modulation of emotional arousal and learning (1K01MH123783-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10041464. Licensed CC0.

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