Glutamatergic excitation suppresses latent cortical pacemaking
- 1Endeavor Health, Evanston, USA
- 2Pritzker School of Medicine, Chicago, USA
- 3Department of Biomedical Engineering, Northwestern University, Evanston, USA.
Abstract
Glutamate provides the principal excitatory drive in the cortex, so reducing ionotropic glutamatergic transmission is expected to suppress neuronal activity. We asked whether reducing ongoing glutamatergic excitation can reveal a previously unrecognized form of neuronal activity: a local population timing mechanism. Combining two established single-neuron constraints (near-threshold susceptibility and spike-history-dependent loss of excitability) we proposed an availability reservoir: a local population can generate a burst only when enough neurons are both susceptible and recovered. This hypothesis predicted a counterintuitive result: local glutamate-receptor antagonism should not simply silence the awake cortex, but should allow the eligible pool to refill and reveal recurrent burst-quiescence. In the awake rabbit cortex, local glutamate-receptor antagonism produced stereotyped local-field-potential and multi-unit population bursts separated by quiescence. Increasing GABAergic inhibition progressively reduced burst size and recurrence before abolishing the pacemaker regime, whereas reducing GABAergic inhibition under baseline conditions produced epileptiform activity with different timing and intra-burst structure. Thus, glutamatergic excitation can mask a recovery-dependent cortical population pacemaker regime. The same framework distinguishes recovery-dependent burst-quiescence from disinhibited epileptiform bursting, providing an operational separation between visually similar but mechanistically different brain states.
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BibTeX
@misc{aksenov2026glutamatergic,
title = {{Glutamatergic excitation suppresses latent cortical pacemaking}},
author = {Daniil P. Aksenov and Evan Doubovikov and Natalya A. Serdyukova and Mohammed M. Minhaj and Steven B. Greenberg},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.26.759671},
url = {https://www.biorxiv.org/content/10.64898/2026.10.26.759671v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Glutamatergic excitation suppresses latent cortical pacemaking
AU - Daniil P. Aksenov
AU - Evan Doubovikov
AU - Natalya A. Serdyukova
AU - Mohammed M. Minhaj
AU - Steven B. Greenberg
PY - 2026
DA - 2026/10/26
PB - bioRxiv
DO - 10.64898/2026.10.26.759671
UR - https://www.biorxiv.org/content/10.64898/2026.10.26.759671v1
AB - Glutamate provides the principal excitatory drive in the cortex, so reducing ionotropic glutamatergic transmission is expected to suppress neuronal activity. We asked whether reducing ongoing glutamatergic excitation can reveal a previously unrecognized form of neuronal activity: a local population timing mechanism. Combining two established single-neuron constraints (near-threshold susceptibility and spike-history-dependent loss of excitability) we proposed an availability reservoir: a local population can generate a burst only when enough neurons are both susceptible and recovered. This hypothesis predicted a counterintuitive result: local glutamate-receptor antagonism should not simply silence the awake cortex, but should allow the eligible pool to refill and reveal recurrent burst-quiescence. In the awake rabbit cortex, local glutamate-receptor antagonism produced stereotyped local-field-potential and multi-unit population bursts separated by quiescence. Increasing GABAergic inhibition progressively reduced burst size and recurrence before abolishing the pacemaker regime, whereas reducing GABAergic inhibition under baseline conditions produced epileptiform activity with different timing and intra-burst structure. Thus, glutamatergic excitation can mask a recovery-dependent cortical population pacemaker regime. The same framework distinguishes recovery-dependent burst-quiescence from disinhibited epileptiform bursting, providing an operational separation between visually similar but mechanistically different brain states.
SN - 2692-8205
ER -