Glutamatergic excitation suppresses latent cortical pacemaking

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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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-10-28
DOI
https://doi.org/10.64898/2026.10.26.759671
Primary Topic
Neural dynamics and brain function
Type
preprint

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preprint

Glutamatergic excitation suppresses latent cortical pacemaking

Evan D. Doubovikov, Daniil P. Aksenov, Mohammed M. Minhaj, Steven B. Greenberg et al.
bioRxiv (Cold Spring Harbor Laboratory)
Neural dynamics and brain function
preprint

Glutamatergic excitation suppresses latent cortical pacemaking

Evan D. Doubovikov, Daniil P. Aksenov, Mohammed M. Minhaj, Steven B. Greenberg, Natalya A. Serdyukova
preprint en

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.

bioRxiv (Cold Spring Harbor Laboratory)
NorthShore University HealthSystem (US)
National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke
Good health and well-being
Neural dynamics and brain function
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Glutamatergic excitation suppresses latent cortical pacemaking — Evan D. Doubovikov, Daniil P. Aksenov, et al. · bioRxiv (Cold Spring Harbor Laboratory) (2026) | TGRS Research Map | TGRS