Abstracts

Rationale: Human and animal studies have demonstrated that temporal lobe epilepsy (TLE) is often accompanied by interictal behavioral abnormalities, such as fear and memory impairment. The amygdala, a temporal lobe structure that has long been recognized for its central role in emotional behavior and memory, also plays an important role in epileptogenesis and epilepsy. Pathophysiological alterations in neuroplasticity in the amygdala, particularly the basolateral nucleus of the amygdala (BLA), are characteristic features of certain psychiatric illnesses, such as anxiety disorders, and may underlie epileptogenesis. Here, we utilize the kindling model of epilepsy, which is known to be associated with increased fear, anxiety and memory disturbances, to gain further insight into the cellular mechanisms involved in epilepsy in the BLA.Methods: To spare the BLA from structural damage, we implanted a bipolar electrode in the right olfactory bulb. Daily constant current stimulations were applied to the bulb starting with the determination of the afterdischarge threshold (ADT; 1ms, 60Hz, 2s, at ADT current). To avoid the effects of acute seizures on the field potential measurements, the animals were sacrificed one week after the 10th generalized seizure was induced. To investigate alterations in neuroplasticity in kindled animals, we used a protocol that included paired pulse stimulation (PPS; two single pulses, 100microsec, 60msec interstimulus interval), and high frequency stimulation (HFS; 100micros, 100Hz, 1s, 2x with 20sec interval). The stimulating electrode was placed over the external capsule and the recording electrode over the BLA.Results: HFS of the external capsule induced an increase in the peak amplitude of the BLA field potentials that lasted over 60 min in naïve and sham kindled rats. In contrast to control animals the HFS-induced increase in peak amplitude of the field potentials recorded from kindled rats declined after 15 to 45 min. PPF was similar in naïve, sham and kindled rats.Conclusions: These results indicate that olfactory bulb kindling causes impairment in synaptic plasticity in the BLA. This is in agreement with our hypothesis that alterations in neuroplasticity in the BLA may be important pathophysiological mechanism underlying epilepsy, related affective disorders and memory impairment. Alterations in the probability of neurotransmitter release do not seem to be relevant for these changes.