# Neuronal mechanisms of cerebellar cognitive function

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2021 · $396,346

## Abstract

Understanding human cognition is one of the cornerstones of the CDC's Healthy Brain Initiative (see
https://www.cdc.gov/aging/healthybrain/). The cerebellum was long perceived as an exclusively motor-related
structure, but it is now also increasingly recognized for its involvement in cognition, in both humans and
animals. In recent years clinical and animal studies have shown that cerebellar activation is correlated with
cognitive functions such as spatial working memory, and that cerebellar neuropathology can cause deficits in
those functions. Cerebellar neuropathology is also known to be correlated with mental illnesses like autism,
schizophrenia, dementia and Alzheimer's disease. Thus, understanding cognitive function and mental
illnesses requires understanding the role of the cerebellum in cognition. However, existing evidence is purely
correlational and a neuronal mechanism for cerebellar cognitive involvement has yet to be identified.
 The main barrier to investigating cerebellar cognitive function is that obtaining causal evidence and
exploring neuronal mechanisms requires experiments involving controlled manipulations of cerebellar
function while simultaneously observing cognitive behavior and neuronal activity. The availability of neuro-
and optogenetic tools, awake-behaving electrophysiological techniques and quantitative tests for cognitive
behaviors in mice now allow this barrier to be surmounted. We propose studies designed to answer
fundamental questions about the role of the cerebellum in cognition using mice as our model organism and
spatial working memory (SWM) as a quantifiable cognitive function known to involve the cerebellum in both
humans and rodents. Our central hypothesis is that the cerebellum controls SWM decision-making by
controlling decision-related coherence of neuronal oscillations between the medial prefrontal cortex (mPFC)
and the hippocampus (HC). The mPFC and HC each are reciprocally connected with the cerebellum and play
key roles in SWM. The decision-making process in SWM tasks is characterized by a temporary increase in
coherence between the mPFC and HC. This decision-related coherence is believed to be a requirement for
normal SWM performance.
 We propose to use a new mouse model of cerebellar dysfunction created by co-PI Sillitoe and
electrophysiological recordings in freely moving mice to test the hypothesis that loss of cerebellar function
causes severe SWM deficits and loss of SWM decision-related coherence increase. We propose to employ
optogenetic techniques to manipulate cerebellar activity during SWM behavior to provide causal evidence for
cerebellar involvement in SWM and to map cerebellar cortical areas involved in controlling SWM. Our
preliminary data strongly support our hypotheses. Our work will broadly impact our understanding of the
role of the cerebellum in cognitive brain function and the mechanisms linking cerebellar neuropathology to
mental illness, which makes this project directly releva...

## Key facts

- **NIH application ID:** 10071884
- **Project number:** 5R01MH112143-04
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** DETLEF H HECK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $396,346
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071884

## Citation

> US National Institutes of Health, RePORTER application 10071884, Neuronal mechanisms of cerebellar cognitive function (5R01MH112143-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10071884. Licensed CC0.

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