Targeting NMDA Receptors to Tune Corticothalamic Circuit Function

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dc.contributor.authorChen, Yangen
dc.contributor.committeechairSwanger, Sharon A.en
dc.contributor.committeememberFox, Michael A.en
dc.contributor.committeememberPan, Yuchin Alberten
dc.contributor.committeememberLearman, Lee A.en
dc.contributor.departmentTranslational Biology, Medicine, and Healthen
dc.date.accessioned2023-02-10T09:00:13Zen
dc.date.available2023-02-10T09:00:13Zen
dc.date.issued2023-02-09en
dc.description.abstractThe somatosensory corticothalamic (CT) circuit processes ascending sensory signals, and disruption to the balance of excitation and inhibition (E/I) within CT circuitry leads to absence seizures, sleep disorders, and attention deficits. E/I balance may be restored by independently modulating excitatory CT input to the ventral posteromedial (VPM) thalamus and inhibitory input to the VPM through the CT-thalamic reticular nucleus (nRT)-VPM pathway. This work revealed novel N-methyl-D-aspartate receptor (NMDAR) nucleus-specific and frequency-dependent functional diversity in the somatosensory CT circuit. Specifically, these findings illustrate the different effects of NMDAR negative modulation in the nRT and the VPM, which offers a method to preferentially decrease high frequency excitatory CT input to the VPM while having no significant effect on nRT activity. These results demonstrate the potential of utilizing NMDAR selective modulators to decrease overall excitation within the somatosensory CT circuit. Further investigation is required to elucidate the precise mechanisms underlying this phenomenon, including where NMDARs are localized at CT synapses and the effect of positive NMDAR modulators on nRT and VPM activity.en
dc.description.abstractgeneralThe sensory gating mechanism helps our brain to select essential sensory information to process. Impairment of this sensory gating has been reported in epilepsy, schizophrenia, and autism. The somatosensory corticothalamic (CT) circuit oversea the sensory gating process by adjusting how much excitation and inhibition signals are integrated into the thalamus. Disruption of the balance of excitation and inhibition (E/I) within CT circuitry leads to the absence seizures, sleep disorders, and attention deficits. Our work revealed one of the glutamate receptors N-methyl-D-aspartate receptor (NMDAR), has nucleus-specific and frequency-dependent functional diversity in the somatosensory CT circuit. By targeting the different NMDAR subunits in the circuit, we were able to preferentially decrease high-frequency excitatory input to the thalamus while having no significant effect on inhibitory input. These results offer the potential to utilize NMDAR selective modulators to decrease overall excitation within the somatosensory CT circuit, which is useful to restore the disrupted E/I balance in the thalamus from a variety of neurological diseases. Further investigation is required to elucidate the precise mechanisms underlying this phenomenon.en
dc.description.degreeMaster of Scienceen
dc.format.mediumETDen
dc.identifier.othervt_gsexam:36422en
dc.identifier.urihttp://hdl.handle.net/10919/113758en
dc.language.isoenen
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectCorticothalamic Circuitsen
dc.subjectNMDA Receptoren
dc.subjectExcitation/Inhibition Balanceen
dc.subjectNMDAR GluN2 subunits.en
dc.titleTargeting NMDA Receptors to Tune Corticothalamic Circuit Functionen
dc.typeThesisen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.levelmastersen
thesis.degree.nameMaster of Scienceen

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