Abstracts

Rationale: Comorbid psychiatric disorders are common in patients with epilepsy. These comorbidities include depression, anxiety, psychoses, and cognitive dysfunctions. It has been extensively documented that temporal lobe epilepsy, the most prevalent form of adult epilepsy in humans, is often associated with interictal memory deficits and negative emotional disturbances. However, the underlying mechanism of seizure-induced emotional impairment is still unclear. We investigated whether amygdala kindling caused chronic interictal behavioural alterations in memory and emotionality. We then correlated the seizure-induced behavioural changes with alterations in excitatory and inhibitory transmissions and in endocannabinoid-mediated plasticity within the amygdala. Methods: Kindling procedure consisted of 20, once daily, electrical stimulations. One week after the last evoked sham or kindled seizure, rats were tested in the elevated plus maze task to assess anxiety and fear conditioning to test fear memory dynamics. In the same rats, patch clamp recordings of pyramidal neurons of the basolateral amygdala were performed to parallel behavioural alterations with changes in glutamate and GABA transmissions and endocannabinoid-mediated short- and long-term synaptic plasticity. Results: Data obtained show alterations of the emotional behaviour (increased anxiety tested with an elevated plus maze task, n= 14 per group) and fear memory (tested in an auditory fear conditioning paradigm, n=25 per group) in rats subjected to amygdala kindling relative to the sham group (p < 0.001, p < 0.05, for anxiety and fear memory tests, respectively). Moreover, behavioural emotional alterations were associated with dysregulation of GABA synaptic transmission (reduced frequency of inhibitory post-synaptic currents, n = 30 cells per group, p < 0.001, sham vs kindled), alteration of endocannabinoid-mediated plasticity at GABAergic synapses (impaired depolarization-induced suppression of inhibition, n = 15 cells per group, p < 0.05, sham vs kindled) and increased glutamate transmission ( increased frequency of spontaneous excitatory post-synaptic currents, n = 6 cells per group, p < 0.05, sham vs kindled). Conclusions: These results indicate that repetitive seizures cause long-lasting changes of the physiology and the endocannabinoid-mediated synaptic plasticity in the amygdala, which are paralleled with emotional disturbances. Funding: "Eyes High" postdoctoral fellowship to RC. "Canadian Institutes of Health Research" research grant to GCT.