Sensory Neurotransmission: AMPA receptors mediate fast evoked responses while NMDA receptors mediate gamma oscillations
Abstract
Discrete auditory stimuli such as tones or clicks evoke brief, time-locked changes in electroencephalographic (EEG) field potentials. Although these responses are small in amplitude, signal averaging across trials reveals robust auditory evoked potentials that serve as translational biomarkers of cortical sensory processing in neuropsychiatric drug development. We recently reported that a modest dose of the NMDA receptor antagonist MK801 (0.05 mg/kg) does not significantly alter tone- or click-evoked responses. In contrast, 40 Hz click-train stimulation induces sustained gamma oscillations that are markedly disrupted by MK801. These findings suggest a mechanistic dissociation between fast stimulus-evoked responses and induced gamma synchrony. We hypothesize that the time-locked evoked response reflects rapid feedforward excitatory neurotransmission mediated primarily by AMPA receptors, whereas 40 Hz induced oscillations represent recurrent cortical network activity that depends predominantly on NMDA receptor signaling. To test this, we examined the effects of the selective AMPA receptor antagonist NBQX on auditory evoked responses and gamma oscillations. Our findings support the interpretation that tone- and click-train–evoked responses are primarily AMPA-mediated, while induced gamma oscillations rely more heavily on NMDA receptor–dependent network dynamics. These results further clarify the receptor-specific mechanisms underlying electrophysiological biomarkers of cortical auditory processing.
Start Time
15-4-2026 1:30 PM
End Time
15-4-2026 4:30 PM
Room Number
Culp Ballroom 316
Poster Number
57
Presentation Type
Poster
Presentation Subtype
Posters - Competitive
Presentation Category
Health
Student Type
Graduate and Professional Degree Students, Residents, Fellows
Faculty Mentor
Sivarao Digavalli
Sensory Neurotransmission: AMPA receptors mediate fast evoked responses while NMDA receptors mediate gamma oscillations
Culp Ballroom 316
Discrete auditory stimuli such as tones or clicks evoke brief, time-locked changes in electroencephalographic (EEG) field potentials. Although these responses are small in amplitude, signal averaging across trials reveals robust auditory evoked potentials that serve as translational biomarkers of cortical sensory processing in neuropsychiatric drug development. We recently reported that a modest dose of the NMDA receptor antagonist MK801 (0.05 mg/kg) does not significantly alter tone- or click-evoked responses. In contrast, 40 Hz click-train stimulation induces sustained gamma oscillations that are markedly disrupted by MK801. These findings suggest a mechanistic dissociation between fast stimulus-evoked responses and induced gamma synchrony. We hypothesize that the time-locked evoked response reflects rapid feedforward excitatory neurotransmission mediated primarily by AMPA receptors, whereas 40 Hz induced oscillations represent recurrent cortical network activity that depends predominantly on NMDA receptor signaling. To test this, we examined the effects of the selective AMPA receptor antagonist NBQX on auditory evoked responses and gamma oscillations. Our findings support the interpretation that tone- and click-train–evoked responses are primarily AMPA-mediated, while induced gamma oscillations rely more heavily on NMDA receptor–dependent network dynamics. These results further clarify the receptor-specific mechanisms underlying electrophysiological biomarkers of cortical auditory processing.
