# Genetic Dissection of Catecholaminergic Innervation of the Cognitive Cerebellum

> **NIH NIH R01** · SEATTLE INST FOR BIOMEDICAL/CLINICAL RES · 2020 · $327,689

## Abstract

Studies in humans and non-human primates have identified a region of the dentate nucleus of
the cerebellum (DCN), or lateral nucleus in rodents (LCN), which is activated during
performance of cognitive tasks involving complex spatial and sequential planning. We have
previously shown that the dopamine D1 receptor marks a population of neurons in the LCN with
similar spatial distribution and regulates cognitive performance on several tasks related to
attention and working memory, and has connections with other parts of the brain that are
classically involved in these functions. The DCN is implicated in cognitive function in humans
with psychiatric illnesses, but virtually nothing is known about its basic anatomical and functional
organization. Unraveling this will set the stage for precision therapeutics in the cognitive domain,
an area where we have few options to offer patients. We hypothesized that the locus ceruleus is
the principal source of both dopamine and norepinephrine release in LCN, catecholamines are
required for cerebellar enhancement of attention and working memory tasks, and locus ceruleus
neurons release catecholamines in a phasic manner. We have mapped projections of the LC to
DCN, and have found that when we electrically stimulate the LC, we can observe catecholamine
release in the LCN with fast scan cyclic voltammetry in anesthetized animals. We have also
found that when we turn off tyrosine hydroxylase expression in the LCN, we get abnormal
performance on sensory discrimination, working memory, and impulsive behaviors. Here we
propose to establish the basic electrophysiological, anatomical, and behavioral function of these
pathways using Cre driver mouse lines in combination with advanced techniques in viral-based
circuit dissection. Successful completion of our proposed aims will provide novel insight into the
basic organization of the LCN and establish a framework for novel, precision therapeutics to
assist patients with cognitive dysfunction.

## Key facts

- **NIH application ID:** 9984833
- **Project number:** 5R01MH116883-03
- **Recipient organization:** SEATTLE INST FOR BIOMEDICAL/CLINICAL RES
- **Principal Investigator:** Erik Sean Carlson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $327,689
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984833

## Citation

> US National Institutes of Health, RePORTER application 9984833, Genetic Dissection of Catecholaminergic Innervation of the Cognitive Cerebellum (5R01MH116883-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984833. Licensed CC0.

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