The hippocampus participates in a pharmacological rat model of absence seizures

Abstract

SUMMARYObjective-Using the gamma-butyrolactone (GBL) model of absence seizures in Long-Evans rats, this study investigated if 2.5-6 Hz paroxysmal discharges (PDs) induced by GBL were synchronized among the thalamocortical system and the hippocampus, and whether inactivation of the hippocampus affected PDs.Methods-Local field potentials were recorded by chronically implanted depth electrodes in the neocortex (frontal, parietal, visual), ventrolateral thalamus and dorsal hippocampal CA1 area. In separate experiments, multiple unit recordings were made at the hippocampal CA1 pyramidal cell layer, or the mid-septotemporal hippocampus was inactivated by local infusion of GABA A receptor agonist muscimol.Results-As PDs developed following GBL injection, coherence of local field potentials at 2.5-6 Hz increased between the hippocampus and thalamus, and between the hippocampus and the neocortex. Hippocampal theta rhythm was disrupted when GBL induced immobility in the rats. The probability of hippocampal multiple unit firing significantly increased at 40 -80 ms prior to the negative peak of thalamic PDs. Coherence between hippocampal multiple unit activity and thalamic field potentials at 2.5-6 Hz was significantly increased after GBL injection. Muscimol infusion to inactivate the mid-septotemporal hippocampus, as compared to saline infusion, significantly decreased the peak frequency of the PDs induced by GBL, decreased 30-120 Hz hippocampal gamma power, and hastened the transition of PDs to 1-2 Hz slow waves.Significance-During GBL induced 2.5-6 Hz PDs, a hallmark of absence seizure, increased synchronization between the hippocampus and the thalamocortical network was indicated by frequency and temporal correlation analysis. These results suggest that the hippocampus was entrained by thalamocortical activity in the present model of absence seizures. Prolonged synchronization of the hippocampus may result in synaptic alterations that may explain the

Cortical and subcortical brain alterations in Juvenile Absence Epilepsy

“…Interestingly, we observed a consistent mesial-temporal lobe volume reduction both with VBM and Freesurfer analyses. This finding is in accordance with recent studies showing hippocampal damage and spatial memory deficits in animal models of absence epilepsy ( Arcaro et al, 2016 , Jafarian et al, 2015 , Marques-Carneiro et al, 2016 ). However, human data on memory impairment in absence epilepsy are still conflicting ( Verrotti et al, 2015 ) and specific studies focusing on cognitive-brain structure correlation should be performed to better analyse this issue.…”

A Critical Evaluation of the Gamma‐Hydroxybutyrate (GHB) Model of Absence Seizures

“…The same was true for the thalamic administration of GHB in monkeys 34. In rats, the overwhelming fMRI 87 and electrophysiology 64,88 evidence supports the presence of SWDs in the hippocampus during GHB-elicited ASs (but see ref 81). …”

Distinct Topographical Patterns of Spike-Wave Discharge in Transgenic and Pharmacologically Induced Absence Seizure Models

“…Second, the traces of SWDs in the GHB model mice tended to have a waxing and waning rhythmic pattern [37, 38] that is attributed to a progressive entrainment of spikes into the oscillation, followed by a progressive desynchronization [39]. A comprehensive analysis based on nonlinear regression of the quadratic curve revealed that 35 out of 43 SWD events in the GHB model showed waxing and waning patterns, although not in all of the channels.…”