Development and Plasticity of Intrinsic Connectivity in the Central Nucleus of the Mouse Inferior Colliculus

Sturm, Joshua (2015) Development and Plasticity of Intrinsic Connectivity in the Central Nucleus of the Mouse Inferior Colliculus. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Proper brain function depends upon the precise organization of neural circuits. In the central auditory system, accurate acoustic processing depends upon the assembly and preservation of tonotopically-organized networks of excitatory and inhibitory synaptic connections.

In this thesis, we investigated the development and plasticity of intrinsic synaptic circuitry in the central nucleus of the mouse inferior colliculus (CNIC), a tonotopically-organized midbrain nucleus that serves as the major subcortical center for auditory integration.
In the CNIC, intrinsic connections comprise the majority of synapses, yet the functional organization of these local networks has remained largely obscure.

In Chapter 2, we mapped the functional organization of intrinsic connections in the CNIC during the first three weeks of postnatal development. We found evidence of robust excitatory and inhibitory intrinsic connections already at postnatal day 2 (P2). Excitatory and inhibitory intrinsic connections underwent a period of dramatic refinement after hearing onset, resulting in a predominance of intrinsic inhibition.

In Chapter 3, we examined the role of hearing experience in directing the maturation of intrinsic CNIC circuits by rearing mice in pulsed white noise. We found that pulsed noise delivered from P12-25, but not P19-25, led to a profound reorganization of excitatory and inhibitory intrinsic connections received by both glutamatergic and GABAergic neurons, suggesting that intrinsic CNIC circuits are sculpted by acoustic experience during an early critical period.

In Chapter 4, we investigated the effects of hearing-loss on the organization of CNIC circuits in a mouse model of tinnitus. We found that hearing loss led to reorganizations of excitatory and inhibitory local CNIC circuits, the nature of which correlated with the presence or absence of behavioral evidence of tinnitus. Acoustic enrichment with pulsed white noise delivered immediately after acoustic trauma prevented circuit reorganization and the emergence of behavioral signs of tinnitus.

In addition to providing the first characterization of functional intrinsic connectivity in the auditory midbrain, our findings may also have broader implications for the principles that govern the organization and balance of excitatory and inhibitory networks in subcortical circuits. Our findings also have potentially important clinical implications for the prevention and treatment of tinnitus.

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Details

Item Type:	University of Pittsburgh ETD
Status:	Unpublished
Creators/Authors:	Creators Email Pitt Username ORCID Sturm, Joshua jjs149@pitt.edu JJS149 0000-0002-4606-5665
ETD Committee:	Title Member Email Address Pitt Username ORCID Committee Chair Meriney, Stephen meriney@pitt.edu MERINEY Thesis Advisor Kandler, Karl kkarl@pitt.edu KKARL Committee Member Urban, Nathaniel N nurban@cmu.edu Committee Member Barth, Alison albarth@cmu.edu Committee Member Chi, David david.chi@chp.edu DHC2 Committee Member Tzounopoulos, Thanos thanos@pitt.edu THANOS Committee Member Lustig, Lawrence lrl2125@cumc.columbia.edu
Date:	25 November 2015
Date Type:	Publication
Defense Date:	19 November 2015
Approval Date:	25 November 2015
Submission Date:	24 November 2015
Access Restriction:	5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages:	226
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 circuit, plasticity, tinnitus, excitation: inhibition balance, GABAergic inhibition, inferior colliculus, auditory midbrain, mouse, laser-scanning photostimulation, glutamate uncaging, synaptic circuit mapping
Date Deposited:	25 Nov 2015 20:03
Last Modified:	25 Nov 2020 06:15
URI:	http://d-scholarship.pitt.edu/id/eprint/26423

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