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Cortical Neuromodulatory Mechanisms of Adaptations to Sound Contrast and their Effects on Contrast-dependent Changes in Pupil Size

Cody, Patrick (2022) Cortical Neuromodulatory Mechanisms of Adaptations to Sound Contrast and their Effects on Contrast-dependent Changes in Pupil Size. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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How does the brain efficiently process such a wide variety of sound environments? Sound environments can be described probabilistically by a change in sound levels across frequency (spectro-) and time (-temporal). To efficiently process sensory signals despite large changes in background noise the brain adapts neural response properties to spectrotemporal sound level statistics. With an increased range of sound levels, spectrotemporal contrast, the slope of neural input-output functions decreases. This gain reduction, termed contrast gain control (CGC), maintains dynamic range enabling cells to discriminate a wider input range. CGC is conserved among species, evident in the midbrain and throughout cortex. CGC accounts for changes in perceptual judgements in humans and mice, however, the underlying cortical neuromodulatory mechanisms remain poorly understood. Furthermore, neural sensory response properties change with internal state factors, such as wakefulness, that can be indexed by pupil-size. However, it is unknown how pupil-indexed internal state changes affect adaptation to sound contrast and whether these cortical adaptations are needed for sound evoked changes in pupil size. To address these questions, we combined pupillometry with 2-photon calcium imaging of layer 2/3 neurons of mouse primary auditory cortex (A1), along with pharmacological and genetic knockout approaches. Our work reveals that contrast-dependent neuromodulatory effects of synaptic zinc are necessary for CGC in A1 and that there are optimal pupil-indexed states for CGC. Further, we report contrast-dependent changes in pupil size that, like CGC, rely upon neuromodulatory zinc signaling in auditory cortex. Thus, we reveal cortical neuromodulatory sensory processing that influences pupil size. In addition to its reported use as a marker for Alzheimer’s disease and schizophrenia, pupil size may therefore serve as a non-invasive clinical marker for disrupted neuromodulatory cortical signaling during sensory adaptation. Understanding context specific neuromodulatory mechanisms of perceptual gain adaptations such as CGC provides insight into other fundamental aspects of perception that rely on gain modulation such as attention and compensation for peripheral hearing loss.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Cody, Patrickpac94@pitt.edupac940000-0002-4618-1340
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairTzounopoulos, Thanosthanos@pitt.eduthanos
Committee MemberKozai, Takashitk.kozai@pitt.edutk.kozai
Committee MemberKuhlman,
Committee MemberSadagopan, Srivatsunvatsun@pitt.eduvatsun
Committee MemberSmith,
Date: 10 June 2022
Date Type: Publication
Defense Date: 10 December 2021
Approval Date: 10 June 2022
Submission Date: 5 April 2022
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 117
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: neuroscience, sensory adaptation, hearing, auditory, hearing in noise, pupillometry, sensory systems, auditory cortex, zinc, synaptic zinc, neuromodulation
Date Deposited: 10 Jun 2022 18:40
Last Modified: 10 Jun 2024 05:15


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