Seizure Susceptibility Corrupts Inferior Colliculus Acoustic Integration

Abstract

Evidence suggests that the pathophysiology associated with epileptic susceptibility may disturb the functional connectivity of neural circuits and compromise the brain functions, even when seizures are absent. Although memory impairment is a common comorbidity found in patients with epilepsy, it is still unclear whether more caudal structures may play a role in cognitive deficits, particularly in those cases where there is no evidence of hippocampal sclerosis. This work used a genetically selected rat strain for seizure susceptibility (Wistar audiogenic rat, WAR) and distinct behavioral (motor and memory-related tasks) and electrophysiological (inferior colliculus, IC) approaches to access acoustic primary integrative network properties. The IC neural assemblies’ response was evaluated by auditory transient (focusing on bottom-up processing) and steady-state evoked response (ASSR, centering on feedforward and feedback forces over neural circuitry). The results show that WAR displayed no disturbance in motor performance or hippocampus-dependent memory tasks. Nonetheless, WAR animals exhibited significative impairment for auditory fear conditioning (AFC) along with no indicative of IC plastic changes between the pre-conditioning and test phases (ASSR coherence analysis). Furthermore, WAR’s IC response to transient stimuli presented shorter latency and higher amplitude compared with Wistar; and the ASSR analysis showed similar results for WAR and Wistar animals under subthreshold dose of pentylenetetrazol (pro-convulsive drug) for seizure-induction. Our work demonstrated alterations at WAR IC neural network processing, which may explain the associated disturbance on AFC memory.

Delving into the significance of the His289Tyr single-nucleotide polymorphism in the glutamate ionotropic receptor kainate-1 (Grik1) gene of a genetically audiogenic seizure model

“…This observation hints at a disturbance in the normal glutamatergic transmission along the primary acoustic pathway, carrying significant implications for the potential propagation of abnormal transmission to the GASH/Sal inferior colliculus (Sánchez-Benito et al, 2020). As in other rodent models of epilepsy, seizure susceptibility corrupts acoustic integration in the IC, a critical structure involved in the initiation propagation of audiogenic seizures (Ribak and Morin, 1995;Pinto et al, 2019). Hence, our findings indicating the overexpression of Grik1 in the IC suggest a potential contribution to heightened excitatory signaling and the potential disruption of neuronal activity balance, even in the absence of seizures.…”

Rodent Brain Pathology, Audiogenic Epilepsy

“…The data obtained also demonstrated that forebrain excitation exert the plausible impact in panic-like behavior of different origin [ 42 ]. Thus, the AE-proneness is, presumably, the cause of IC auditory function disorder [ 43 , 44 ].…”

Active probing to highlight approaching transitions to ictal states in coupled neural mass models

“…Auditory stimuli were used to reveal the pathophysiology of mTLE, where altered neural synchronization induced by monaural pure-tone stimulation [30] or by ASSR [19] may provide useful diagnostic information. ASSRs were also used to analyze ictal and interictal state dynamics in an audiogenic seizure model, demonstrating that responses in this model are enhanced and hypersynchronous [31] in addition to the impairment of auditory processing integration [32]. Electrical stimuli in the form of either cortical or DBS (Deep Brain Stimulation) have been used to monitor neuronal excitability and predict the occurrence of seizures in patients with epilepsy [7,25,33].…”