Abstract
Early life stress results in an enduring vulnerability to kindling-induced epileptogenesis in rats, but the underlying mechanisms are not well understood. Recent studies indicate the involvement of thalamocortical neuronal circuits in the progression of kindling epileptogenesis. Therefore, we sought to determine in vivo the effects of early life stress and amygdala kindling on the firing pattern of hippocampus as well as thalamic and cortical neurons. Eight week old male Wistar rats, previously exposed to maternal separation (MS) early life stress or early handling (EH), underwent amygdala kindling (or sham kindling). Once fully kindled, in vivo juxtacellular recordings in hippocampal, thalamic and cortical regions were performed under neuroleptic analgesia. In the thalamic reticular nucleus cells both kindling and MS independently lowered firing frequency and enhanced burst firing. Further, burst firing in the thalamic reticular nucleus was significantly increased in kindled MS rats compared to kindled EH rats (p<0.05). In addition, MS enhanced burst firing of hippocampal pyramidal neurons. Following a stimulation-induced seizure, somatosensory cortical neurons exhibited a more pronounced increase in burst firing in MS rats than in EH rats. These data demonstrate changes in firing patterns in thalamocortical and hippocampal regions resulting from both MS and amygdala kindling, which may reflect cellular changes underlying the enhanced vulnerability to kindling in rats that have been exposed to early life stress.
Highlights
Mesial temporal lobe epilepsy (MTLE) is the most common form of focal epilepsy in adults, and is often drug resistant [1]
Compared to early handling (EH) rats, maternal separation (MS) rats showed a significantly increased anxiety-like behaviour as evidenced by a significantly lower number of inner circle entries (p = 0.046) as well as less total time spent in the inner circle (p = 0.037) (Figure 1)
This study investigated the effect of early life stress induced by MS and amygdala kindling on in vivo neuronal firing patterns in brain structures relevant to the progression of limbic seizures induced by amygdala kindling
Summary
Mesial temporal lobe epilepsy (MTLE) is the most common form of focal epilepsy in adults, and is often drug resistant [1]. The percentage of burst firing observed in the TRN and the hippocampal pyramidal neurons from all rats were correlated with the number of kindling stimulations delivered for each rat to reach a fully kindled state.
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