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Mechanisms of Intrinsic Plasticity in Mouse Auditory Cortex after Peripheral Damage

Henton, Amanda (2022) Mechanisms of Intrinsic Plasticity in Mouse Auditory Cortex after Peripheral Damage. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Hearing loss, or damage to the peripheral auditory system more generally, initiates many plastic processes that work to compensate for reduced input to auditory cortex (AC). This plasticity in AC allows for the remarkable recovery of basic auditory function, despite profound and permanent hearing loss. Importantly, some functional aspects of hearing do not recover, and this damage may also lead to pathological states such as tinnitus and hyperacusis. Recent studies have provided insight into these plastic processes underlying the functional recovery of AC after noise exposure. Namely, the plasticity of Parvalbumin-positive (PV) neurons in AC has been demonstrated to underlie, and even predict cortical recovery after peripheral auditory damage. It has been proposed that PVs regulate this plasticity by rapidly reducing inhibition to principal neurons (PNs) to allow for homeostatic scaling of excitatory responses. However, many questions remain regarding peripheral damage-induced plasticity. Namely, it is unknown how, of if the intrinsic excitability of excitatory and inhibitory neuron subtypes is modulated, the time dependence of plasticity, and the ion channel mechanisms underlying intrinsic plasticity. To address these open questions, we recorded intrinsic excitability parameters from interneuron subtypes, PV and Somatostatin (SOM) as well as PNs one and seven days after noise exposure (NE). Our studies reveal an acute reduction in PV intrinsic excitability one day after noise exposure, as evidenced by reduced firing rate, accompanied by depolarization of the action potential threshold and hyperpolarization of the resting membrane potential. Further, we found that noise-induced increase in KCNQ channel function, via a shift in the voltage gating, contributes to the observed reduction of intrinsic plasticity of PVs one day after exposure. These studies provide both a cell and ion channel specific mechanism of noise-induced AC plasticity at acute time points after noise exposure. These studies may inform future treatments that could harness these existing plasticity mechanisms to enhance auditory recovery after peripheral auditory damage or mitigate disorders involving maladaptive plasticity such as in tinnitus and hyperacusis.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Henton, Amandaamh296@pitt.eduamh296
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSadagopan,
Thesis AdvisorTzounopoulos,
Committee MemberAizenman,
Committee MemberRunyan,
Committee MemberWilliamson,
Committee MemberTakesian,
Date: 8 August 2022
Date Type: Publication
Defense Date: 15 June 2022
Approval Date: 8 August 2022
Submission Date: 20 June 2022
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 160
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Neurobiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Hearing Loss, Auditory Cortex, KCNQ channels, Interneurons, Noise Exposure
Date Deposited: 08 Aug 2022 23:36
Last Modified: 08 Aug 2022 23:36


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