Phase‐dependent modulation of cortical and thalamic sensory responses during spike‐and‐wave discharges

Abstract

Objective The neuronal underpinnings of impaired consciousness during absence seizures remain largely unknown. Spike‐and‐wave (SW) activity associated with absences imposes two extremely different states in cortical neurons, which transition from suprathreshold synaptic depolarizations during spike phases to membrane hyperpolarization and electrical silence during wave phases. To investigate whether this rhythmic alternation of neuronal states affects the processing of sensory information during seizures, we examined cortical and thalamic responsiveness to brief sensory stimuli in the different phases of the epileptic cycle. Methods Electrocorticographic (ECoG) monitoring from the primary somatosensory cortex combined with intracellular recordings of subjacent pyramidal neurons, or extracellular recordings of somatosensory thalamic neurons, were performed in the Genetic Absence Epilepsy Rat From Strasbourg. Sensory stimuli consisted of pulses of compressed air applied to the contralateral whiskers. Results Whisker stimuli delivered during spike phases evoked smaller depolarizing synaptic potentials and fewer action potentials in cortical neurons compared to stimuli occurring during wave phases. This spike‐related attenuation of cortical responsiveness was accompanied by a reduced neuronal membrane resistance, likely due to the large increase in synaptic conductance. Sensory‐evoked firing in thalamocortical neurons was also decreased during ECoG spikes as compared to wave phases, indicating that time‐to‐time changes in the thalamocortical volley may also contribute to the variability of cortical responses during seizures. Significance These findings demonstrate that thalamocortical sensory processing during absence seizures is nonstationary and strongly suggest that the cortical impact of a given environmental stimulus is conditioned by its exact timing relative to the SW cycle. The lack of stability of thalamic and cortical responses along seizures may contribute to impaired conscious sensory perception during absences.

Neuronal excitability and sensory responsiveness in the thalamo‐cortical network in a novel rat model of isoelectric brain state

“…In control conditions, the firing probability of thalamo-cortical cells in response to sensory stimuli was 0.49 ± 0.37 (n = 9 neurons). The corresponding mean number of sensory-evoked APs per stimulation was 1.30 ± 0.40 (n = 9 neurons) and the latency of the first evoked AP, relative to air-puff onset, was 17.1 ± 4.7 ms (n = 9 neurons), a value similar to that previously reported for the same cell population (Brecht & Sakmann, 2002;Williams et al 2020) and compatible with the latency of cortical neurons dPSPs (13-20 ms). Sensory responsiveness of thalamo-cortical neurons was found to be largely reduced during the electro-cerebral inactivity.…”

“…A similar injection protocol, using greater current intensities (2–5 nA) granted a reliable labelling of the juxta‐cellularly recorded cells (Williams et al . 2020). Rats were then rapidly killed with euthasol and transcardially perfused with a fixative solution containing 0.3% glutaraldehyde‐4% paraformaldehyde in phosphate‐buffered saline (0.1 m , pH 7.4) (VWR Chemicals, Fontenay‐sous‐Bois, France).…”

“…A reliable labelling of intra-cellularly recorded neurons was achieved by means of repeated injection of depolarizing current pulses (0.2-1 nA; 300 ms) applied at 3 Hz during 10-20 min at the end of the recording session (Mahon & Charpier, 2012). A similar injection protocol, using greater current intensities (2-5 nA) granted a reliable labelling of the juxta-cellularly recorded cells (Williams et al 2020). Rats were then rapidly killed with euthasol and transcardially perfused with a fixative solution containing 0.3% glutaraldehyde-4% paraformaldehyde in phosphate-buffered saline (0.1 m, pH 7.4) (VWR Chemicals, Fontenay-sous-Bois, France).…”

Variation and convergence in the morpho-functional properties of the mammalian neocortex

“…The reason for the higher frequency of spike-wave oscillations in rodents is not yet well understood, but experimental and theoretical work has proposed that it may involve species differences in the prevalence of GABAergic receptor subtypes affecting the duration of the oscillatory cycle (Destexhe, 1999;Destexhe et al, 1999;Sanchez-Vives et al, 2021). Consistent findings in cats and rats show that these abnormal oscillations dynamically alter the intrinsic excitability of cortical neurons, impeding their ability to integrate and process sensory information efficiently (Neckelmann et al, 2000;Williams et al, 2016Williams et al, , 2020. It has therefore been suggested that such instability of sensory representations during seizures may contribute to impairing the cortical functions necessary for normal conscious experience (Williams et al, 2020).…”

Comparison of anaesthetic- and seizure-induced states of unconsciousness: a narrative review

“…77,165 Moreover, regions in the brain during absence seizures show decreases in CBF and metabolism. 166 It is unclear if the anaesthetic reductions in CBF and metabolic activity cause unconsciousness or if they are a result of alterations in network interactions. 33 Patients recovering from a vegetative state who regained consciousness, for example, continued to show substantially decreased global cerebral metabolism.…”