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Differences in excitatory and inhibitory neuron oxygen metabolism elucidated by intrinsic optical imaging and optogenetics in awake mice

Toader, Andrew E. (2022) Differences in excitatory and inhibitory neuron oxygen metabolism elucidated by intrinsic optical imaging and optogenetics in awake mice. Undergraduate Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Neurons rely on a continuous supply of oxygen to sustain their function. Many studies have shown that metabolic consumption is proportional to overall brain activity, but it is not clear whether oxygen metabolism is different between excitatory and inhibitory neurons, the two major neuronal subtypes. It is thought that dysfunction in excitatory and inhibitory neurons plays a key role in the pathologies of various diseases including Epilepsy and Alzheimer’s Disease. This work examined potential differences in the cerebral rate of oxygen metabolism (CMRO2) between excitatory and inhibitory cortical neurons using optical imaging methods sensitive to blood oxygenation. Manipulation of excitatory and inhibitory neurons was facilitated using optogenetics to selectively manipulate the activity of these neurons. Our results suggest that optogenetic activation of excitatory neurons is less metabolically expensive than optogenetically activating inhibitory neurons by as much as a factor of 6.9 (range from 0.76 to 6.9). The low-end of this range does not consider that excitatory neurons outnumber inhibitory neurons in cortex by about 4:1, still providing support for inhibitory neurons consuming more oxygen than excitatory neurons under awake conditions. We compared these results to our previous study conducted under light ketamine anesthesia using similar experimental procedures where optogenetic activation of inhibitory neurons was more metabolically expensive than activating excitatory neurons by a factor of 2.6. Understanding the oxygen consumption of neuronal subtypes can elucidate functional disturbances in areas across the brain and may aid in the discovery of various therapeutic modalities for diseases that preferentially target genetically distinct populations of neurons.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Toader, Andrew E.andrew.toader@pitt.eduaet370000-0002-7530-9200
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorVazquez, Alberto L.alv15@pitt.edualv15
Committee MemberZhan, Liangliang.zhan@pitt.eduliang.zhan
Committee MemberAkcakaya, Muratakcakaya@pitt.eduakcakaya
Committee MemberFukuda, Mitsuhirohiro.fukuda@pitt.eduhiro.fukuda
Committee MemberKainerstorfer, Janajkainers@andrew.cmu.edu
Date: 23 April 2022
Date Type: Publication
Defense Date: 13 April 2022
Approval Date: 23 April 2022
Submission Date: 18 April 2022
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 84
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Computer Engineering
University Honors College
Degree: BSE - Bachelor of Science in Engineering
Thesis Type: Undergraduate Thesis
Refereed: Yes
Uncontrolled Keywords: CMRO2, optogenetics, neuro-metabolic coupling, oxygen metabolism
Date Deposited: 23 Apr 2022 19:21
Last Modified: 23 Apr 2022 19:21
URI: http://d-scholarship.pitt.edu/id/eprint/42649

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  • Differences in excitatory and inhibitory neuron oxygen metabolism elucidated by intrinsic optical imaging and optogenetics in awake mice. (deposited 23 Apr 2022 19:21) [Currently Displayed]

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