# Defining a thalamic role in premotor cortical sequence generation

> **NIH NIH F31** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $39,539

## Abstract

PROJECT SUMMARY
Sequential neural activity is ubiquitous throughout the brain and is thought to underly many essential processes
from working memory to complex motor behavior. However, the mechanisms of sequence generation still remain
unknown; whether neural sequences are generated locally or emerge from the cooperation between local circuits
and long-range inputs is controversial. For example, input from thalamic regions has been shown to be involved
in the sequential activity that occurs in cortex during skilled motor acts. The adult male zebra finch provides an
ideal system to investigate mechanisms of cortical sequence generation. After learning his courtship song
through months of extensive practice as a juvenile, the zebra finch produces a stereotyped song composed of
repeated complex vocal elements known as syllables. Proper song production requires the coordinated action
of multiple nuclei across the song-production network, including two cortical regions, HVC (proper name) and
the robust nucleus of the arcopallium (RA) and the thalamic nucleus uvaeformis (Uva). While lesion studies have
shown the importance of Uva to song production, the role of these thalamic inputs in facilitating the sequential
activity in HVC and RA is still unclear. In this proposal, I will test three models of sequence generation in the
zebra finch song-production network, each of which attributes a different role to the thalamus in shaping cortical
sequences. In model 1, thalamic input is required for moment-to-moment progression through the cortical
sequence. In model 2, thalamic input is necessary to link discrete cortical sequences encoding individual
syllables. In model 3, the thalamus acts to orchestrate progression through a continuous cortical sequence that
encodes the entire song. Previous studies have sought to distinguish between these models by assessing the
behavioral impact of lesioning Uva. Lesions eliminate singing behavior, thus precluding any opportunity to study
the circuit. However, sleep provides the opportunity to probe this circuit, where song-like `replay' fragments have
been observed in individual cortical neurons and neuron pairs without subsequent vocalizations. I will first adapt
high-density silicon probe technology for the zebra finch and build analytical tools to decode the song-content of
sleep replay. Next I will investigate the role of thalamic input in cortical sequence generation by perturbing this
input and determining the impact this perturbation has on cortical replay. In this way, I will uncover the role of
thalamic input in cortical sequences underlying complex skilled behavior in the zebra finch. These experiments
will increase our understanding of how thalamic inputs contribute to cortical dynamics in healthy networks and
provide insight into pathological processes that disrupt these dynamics during disease.

## Key facts

- **NIH application ID:** 9990477
- **Project number:** 1F31NS116933-01
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Margot Elmaleh
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $39,539
- **Award type:** 1
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990477

## Citation

> US National Institutes of Health, RePORTER application 9990477, Defining a thalamic role in premotor cortical sequence generation (1F31NS116933-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9990477. Licensed CC0.

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