Author ORCID Identifier

https://orcid.org/0000-0002-4251-5913

Semester

Fall

Date of Graduation

2024

Document Type

Dissertation

Degree Type

PhD

College

School of Medicine

Department

Not Listed

Committee Chair

Charles Anderson

Committee Member

Martin Hruska

Committee Member

Kevin Daly

Committee Member

Gary Marsat

Committee Member

Ariel Agmon

Abstract

Synaptic zinc signaling modulates synaptic activity and is present in specific populations of cortical neurons, suggesting that synaptic zinc contributes to the diversity of intracortical synaptic microcircuits and their auditory tuning properties. Stimulus-specific adaptation is a hallmark of sensory processing in which a repeated stimulus results in diminished successive neuronal responses, but a deviant stimulus will still elicit robust responses from the same neurons. Recent work has established that synaptically released zinc is an endogenous mechanism that shapes neuronal responses to sounds in the auditory cortex. Here, to understand the role of zinc signaling in the auditory cortex and the impact it has on auditory neuronal tuning properties as well as to understand the contributions of synaptic zinc to deviance detection of specific neurons, we performed in vivo wide field and 2-photon calcium imaging of multiple classes of intratelencephalic (IT) neurons and extratelencephalic (ET) neurons in layer 5 of the mouse auditory cortex. We found that changes in synaptic zinc can widen or sharpen the sound-frequency tuning bandwidth of IT neurons but only widen the tuning bandwidth of ET neurons. These results provide evidence for synapse- and cell-type-specific actions of synaptic zinc in the cortex. We also find that IT neurons in both layer 2/3 and 5 as well as corticocollicular ET neurons in layer 5 all demonstrate deviance detection, however, we find a specific enhancement of deviance detection in corticocollicular neurons that arises from ZnT3-dependent synaptic zinc in layer 2/3 IT neurons. Genetic deletion of ZnT3 from layer 2/3 IT neurons removes the enhancing effects of synaptic zinc on corticocollicular neuron deviance detection resulting in poorer acuity of detecting deviant sounds by behaving mice.

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