# Dendritic morphology, patterns of input, and calcium signal heterogeneity in a novel subpopulation of cerebellar Purkinje cells

> **NIH NIH F31** · UNIVERSITY OF CHICAGO · 2023 · $47,594

## Abstract

Project Summary
 The cerebellum optimizes motor and non-motor performance by integrating input signals encoding
prediction error with input relaying a spectrum of multisensory and contextual information. These input
pathways–carried by climbing fiber axons (CFs) from the inferior olive and parallel fiber axons (PFs) of
cerebellar granule cells, respectively–converge on the elaborate dendritic arbor of Purkinje cells (PCs), the
primary cell type and sole output of the cerebellar cortex. Theories of cerebellar function are centered around
PC-mediated integration and rely on the principles that each PC: 1) is a structurally and functionally redundant
unit in the cerebellar cortex, 2) receives olivary ‘teaching’ signal input from only one CF, and 3) exhibits
homogenous signaling across the entire dendritic tree.
 The specific aims of this proposal are designed to challenge the universality of these principles by
revealing a ‘super-integrator’ PC subpopulation characterized by input from multiple CFs and non-homogenous
signaling across dendrites. These PCs are defined morphologically by segregated dendritic compartments
from either the early bifurcation of their primary dendrite (‘Split’) or multiple primary dendrites emerging from
the soma (‘Poly’). ‘Super-integrator’ PCs are defined functionally by the presence of non-homogenous dendritic
signaling produced by independent input to each compartment, such as from multi-CF innervation.
 This study will examine the anatomical CF→PC connection, describe signal heterogeneity in PC dendritic
compartments, and examine how these functional elements affect integration during multisensory processing.
To comprehensively assess these anatomical and functional features of PCs, experiments will be balanced
between tightly controlled in vitro preparations and physiologically relevant in vivo conditions and will combine
electrophysiology, Ca2+ imaging, and tracer immunolabeling methods. A central training goal of this proposal is
to learn and apply a range of techniques, especially by pairing Ca2+ imaging and electrophysiology, and data
analysis methods toward my development as an independent researcher.
 The final results of this work will provide a significant update to our current understanding of fundamental
cerebellar anatomy and function. This update will introduce a panel of new research questions to better
understand task-dependent cerebellar computations, expansion and compression of information as it flows
through cerebellar circuits, and sources of dysfunction in disease as putative targets for therapy. Some
features of ‘super-integrator’ PCs in wildtype animals (e.g. abnormal CF inputs and multi-compartment
morphology) overlap with features that are overexpressed in mouse models of autism spectrum disorder. It is
possible that, in addition to conferring normal cerebellar function, an overabundance of ‘super-integrator’ PCs
may underlie some characteristics of cerebellar dysfunction in autism.

## Key facts

- **NIH application ID:** 10656273
- **Project number:** 5F31NS129256-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Silas Edward Busch
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $47,594
- **Award type:** 5
- **Project period:** 2022-07-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10656273

## Citation

> US National Institutes of Health, RePORTER application 10656273, Dendritic morphology, patterns of input, and calcium signal heterogeneity in a novel subpopulation of cerebellar Purkinje cells (5F31NS129256-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10656273. Licensed CC0.

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