Recent reports in human demonstrate a role of theta-gamma coupling in memory for spatial episodes and a lack of coupling in people suffering from temporal lobe epilepsy, but the mechanisms are unknown. Using multisite silicon probe recordings of epileptic rats engaged in episodic-like object recognition tasks we sought to evaluate the role of theta-gamma coupling in the absence of epileptiform activities. Our data reveal a specific association between theta-gamma (30-60 Hz) coupling at the proximal stratum radiatum of CA1 and spatial memory deficits. We targeted the microcircuit mechanisms with a novel approach to identify putative interneuronal types in tetrode recordings (parvalbumin-basket cells in particular) and validated classification criteria in the epileptic context with neurochemical identification of intracellularly recorded cells. In epileptic rats, putative parvalbumin basket cells fired poorly modulated at the falling theta phase, consistent with weaker inputs from Schaffer collaterals and attenuated gamma oscillations, as evaluated by theta phase decomposition of current-source density signals. We propose that theta-gamma interneuronal rhythmopathies of the temporal lobe are intimately related to episodic memory dysfunction in this condition.
Significance statement: Cognitive deficits of temporal lobe epilepsy represent a major co-morbidity of this disease, but how epileptogenic microcircuits serve cognitive demands during seizure free periods remain poorly understood. Here, we investigate this issue using an experimental rat model of temporal lobe epilepsy. Our data link hippocampal theta phase-specific uncoupling in the slow gamma band with disruption of episodic-like memory function and microcircuit deficits resulting from poor oscillatory firing of parvalbumin basket cells.
The authors declare no competing financial interests.
MINECO | Consejo Superior de Investigaciones Científicas (CSIC) [BFU2012-37156-C03-01]; Spanish Ministry of Education, Culture and Sports [FPU12/03776]