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Developmental changes in mouse motor by skill learning and cortical circuitry

Kim, Taehyeon (2025) Developmental changes in mouse motor by skill learning and cortical circuitry. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Learning motor skills requires plasticity in the primary motor cortex (M1), including changes in inhibitory circuitry. But how inhibitory synaptic connections change during skill acquisition and whether this varies over development is not fully understood. This study assesses the normal developmental trajectory of motor learning and then addresses inhibitory connectivity changes after motor learning. We trained mice of both sexes to run on a custom accelerating rotarod at ages from postnatal day (P) 20 to P120, tracking paw position and quantifying time to fall and changes in gait pattern. Performance improved most rapidly between P30-60, while paw position and gait patterns change with learning, though differently between age groups. To address circuit changes, we labeled task-active and task-inactive pyramidal cells with CaMPARI2, a genetically encoded activity marker. We then evoked inhibitory responses (IPSCs) from two major interneuron types: parvalbumin-expressing (PV+) interneurons and somatostatin-expressing (SST+) interneurons. After one training day, PV-mediated inhibition is greater in the active cells, while SST-mediated inhibition is not different. These results suggest early changes in PV-mediated inhibition may support motor skill acquisition in mice. Whether PV-mediated inhibitory changes persist or changes in SST+ interneuron connections arise later in training remains to be tested.

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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Kim, Taehyeontak127@pitt.edutak127
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorHooks, Bryan M.hooksm@pitt.edu
Committee ChairSeal, Rebeccarpseal@pitt.edu
Committee MemberGharbawie, Omaromar@pitt.edu
Committee MemberRunyan, Carolinerunyan@pitt.edu
Committee MemberBarth, Alisonalbarth@andrew.cmu.edu
Committee MemberChen, Simon X.schen2@uottawa.ca
Date: 13 February 2025
Date Type: Publication
Defense Date: 3 September 2024
Approval Date: 13 February 2025
Submission Date: 13 November 2024
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 202
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Neurobiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: motor learning; primary motor cortex; development; critical period; inhibition; synaptic plasticity; parvalbumin; somatostatin
Date Deposited: 13 Feb 2025 20:09
Last Modified: 13 Feb 2025 20:09
URI: http://d-scholarship.pitt.edu/id/eprint/47059

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