# Cerebellar Output Circuits

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $385,169

## Abstract

Proposal Summary
DESCRIPTION (provided by applicant): Impairments in prefrontal cortical function are
associated with many psychiatric disorders, including schizophrenia, mood disorders,
and autism. Surprisingly, the vermis - a small part of the cerebellum best known for its
role in posture and eye movements - has been strongly implicated in each of these
disorders. Deficits in executive control of saccadic eye movements are used as
biomarkers for schizophrenia, autism, and depression, consistent with a dual role of the
vermis in regulating both motoric and prefrontal cortical function. However, neither the
neural circuit substrates that link the cerebellar vermis with the prefrontal cortex nor the
functional impact of these connections are understood. The central hypothesis of this
proposal is that the affective and cognitive functions of the cerebellar vermis are
mediated by a specific class of cerebellar nucleus neuron that makes circuit connections
with the reticular activating system, a critical regulator of arousal and cortical state, as
well as with neurons of the medial thalamus that are essential for prefrontal cortical
function. The proposed experiments will test this hypothesis with a combination of
modern anatomical, physiological, pharmacological, optogenetic, and behavioral
strategies. Deficits in cerebellar engagement with the reticular activating system and the
thalamus could account for mood dysregulation and cognitive deficits common to several
psychiatric disorders. Accomplishing the aims of the proposed research will result in
unprecedented cell type specific information about the long-range circuit connections
that link the cerebellar vermis with the prefrontal cortex that account for cerebellar
modulation of affective and cognitive function. This research will thus generate new
insights into the mechanisms that mediate currently unexplained efficacy of transcranial
stimulation of the cerebellum in improving cognitive and mood dysfunction in psychiatric
disorders.

## Key facts

- **NIH application ID:** 10158334
- **Project number:** 5R01NS105039-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** SASCHA DU LAC
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $385,169
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10158334

## Citation

> US National Institutes of Health, RePORTER application 10158334, Cerebellar Output Circuits (5R01NS105039-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10158334. Licensed CC0.

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