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Synaptic basis of temporal learning in the cerebellum

Award Number: R01NS146497
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/19/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2031

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Synaptic basis of temporal learning in the cerebellum - PROJECT SUMMARY/ABSTRACT: Animal survival requires that the brain use dynamic sensory information from the environment to generate precise motor actions. Transient, sequential activation of neurons within a population is a coding framework that can be a substrate for structuring motor actions within a dynamical sensory framework. Such neural sequences are observed across many brain regions and can be used as a set of mathematical functions to learn precisely timed neural activity dynamics. How they are generated and regulated is less well-known. Cerebellar granule cells (GCs) are thought to encode sensory information as a temporal basis, but their population activity on the subsecond timescale has not been measured. This proposal investigates how synaptic diversity in the cerebellum can sculpt GC temporal basis sets to enable precise sensory-motor transformations underlying motor behaviors. Aim 1 will determine how heterogeneity in mossy fiber–granule cell (MF-GC) synaptic strength and short-term plasticity, both within and across cerebellar regions, generate diverse GC firing patterns using ex vivo patch-clamp recordings and calcium imaging. Aim 2 will assess the in vivo role of synaptic diversity following sensory stimuli and optogenetic stimulation of MFs. MF and GC activity will be evaluated with high-speed two-photon calcium imaging, and neurotransmitter release at the MF- GC synapse will be monitored using a fluorescent glutamate sensor (iGluSnFR). Causal perturbations using chemogenetic modulation of MF neurotransmitter release will test how synaptic properties influence GC temporal dynamics. Aim 3 will determine how synaptic diversity-dependent GC temporal bases encode dynamic MF inputs during a forelimb-reaching task. This will be achieved using pathway-specific imaging, optogenetic MF stimulation at varying frequencies, and chemogenetic modulation of neurotransmitter release to establish causal links between synaptic dynamics and motor precision. By integrating biophysical analysis of synaptic transmission and spiking, high-speed fluorescence imaging, optogenetic stimulation of different MF pathways, chemogenetic modulation, and behavioral approaches, this work will reveal how synaptic diversity generates a temporally tiled representation in the granule cell layer to support associative learning during a reach-to-grab task. By linking biophysical diversity of synaptic transmission to circuit-level representations and behavior, this work will reveal how short-term synaptic plasticity organizes temporally tiled activity in the cerebellar cortex at the service of learning precise motor behaviors.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $622,687 )
2026	2026	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/18/2026	NEW	$622,687
														Subtotal = $622,687

Grand Total All Awards = $622,687

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Synaptic basis of temporal learning in the cerebellum

Award Number: R01NS146497

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/19/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2031

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