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INTRINSIC AND SYNAPTIC MECHANISMS CONTROLLING THE EXCITABILITY OF LAYER 5 CORTICOCALLOSAL AND CORTICOCOLLICULAR NEURONS IN AUDITORY CORTEX

Joshi, Ankur (2016) INTRINSIC AND SYNAPTIC MECHANISMS CONTROLLING THE EXCITABILITY OF LAYER 5 CORTICOCALLOSAL AND CORTICOCOLLICULAR NEURONS IN AUDITORY CORTEX. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Auditory cortex (AC) layer (L) 5B contains both corticocollicular neurons, a type of pyramidal-tract neuron projecting to the inferior colliculus, and corticocallosal neurons, a type of intratelencephalic neuron projecting to contralateral AC. It is known that these neuronal types display dichotomous in vivo responses to sound. While corticocollicular neurons display robust evoked responses to wide range of sound frequencies, corticocallosal neurons are responsive to a limited range of sound frequencies. However, the intrinsic and synaptic mechanisms shaping these dichotomous responses remain unexplored. It is also known that corticocollicular neurons are critical for learning-induced plasticity involved in relearning sound localization after monaural occlusion. This learning induced-plasticity also requires the release of acetylcholine (ACh) in the AC. However, the effect of ACh release on the excitability of corticocollicular neurons is unknown. Therefore, we recorded in brain slices of mouse AC from retrogradely labeled corticocollicular and neighboring corticocallosal neurons in L5B to identify the intrinsic and synaptic mechanisms that contribute to the in vivo responses of these neurons to sound, and to examine the effect of ACh release on corticocollicular and corticocallosal neurons to identify cell-specific mechanisms that enable corticocollicular neurons to participate in relearning sound localization. In comparison to corticocallosal neurons, corticocollicular neurons display a more depolarized resting membrane potential, faster action potentials and less spike frequency adaptation. In paired recordings between single L2/3 and labeled L5B neurons, trains of EPSCs showed no synaptic depression in L2/3→corticocollicular connections, but substantial depression in L2/3→corticocallosal connections. We propose that these differences in intrinsic and synaptic properties contribute to the dichotomous in vivo responses of corticocallosal and corticocollicular neurons to sound. Additionally, ACh release generates nicotinic acetylcholine receptor (nAChR)-mediated depolarizing potentials in both corticocallosal and corticocollicular neurons, but muscarinic acetylcholine receptor (mAChR)-mediated hyperpolarizing potentials in corticocallosal neurons and mAChR-mediated prolonged depolarizing potentials in corticocollicular neurons. This prolonged mAChR-mediated depolarizing potential leads to persistent firing in corticocollicular neurons, whereas corticocallosal neurons lacking this prolonged mAChR-mediated depolarizing potential do not fire persistently. We propose that this mAChR-mediated persistent firing in corticocollicular neurons may be a mechanism required for relearning sound localization after monaural occlusion.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Joshi, Ankuranj39@pitt.eduANJ39
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairAizenman, Eliasredox@pitt.edu
Date: 20 May 2016
Date Type: Publication
Defense Date: 7 December 2015
Approval Date: 20 May 2016
Submission Date: 4 January 2016
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 130
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Neurobiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Auditory, Cortex, Corticocallosal, Corticocollicular, Synaptic, Intrinsic
Date Deposited: 20 May 2016 15:14
Last Modified: 15 Nov 2016 14:31
URI: http://d-scholarship.pitt.edu/id/eprint/26715

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