Abstracts

Rationale: Temporal lobe epilepsy is often related to a lesion induced by an early initial brain injury. Hippocampus and entorhinal cortex are damaged in this pathology and involved in the epileptogenic process. Here we tested the consequences of the neonatal lesion of the ventral hippocampus 7 days after birth, on brain excitability and GABAergic system of adult rats. Methods: Rats pups, 7 day-old were anesthetized and injected bilaterally with 0.3 μl ibotenic acid (10 μg/μl) in the ventral hippocampus. Sham-operated rats received 0.3 μl of artificial cerebrospinal fluid. For excitability measurements, pentylenetetrazol (PTZ; 10 mg/kg) was infused in the tail vein of adult rats at a constant rate of 3 ml/h. The clinical and EEG thresholds for each seizure pattern were compared between lesioned and sham-operated rats. Immunohistochemical staining for markers of interneurons and their projections including calretinin (CR), calbindin (CB), parvalbumin (PV), glutamate decarboxylase (GAD) and type 1 GABA transporter (gat-1) were performed on 20 μm brain sections. Immunopositive neurons were counted and compared in the two groups. Results: The electroclinical course of PTZ-induced seizures was similar in the two groups. The lesioned group exhibited lower thresholds for absence seizures (16 and 8 mg/kg for sham and lesioned rats, respectively) and slightly higher thresholds for clonic seizures (32 and 39 mg/kg for sham and lesioned rats, respectively). No significant difference could be observed for myoclonic seizures between the two groups. No rat of any group developed spontaneous seizures. The number of PV-, CB- and CR-positive neurons was decreased in lesioned rats in the pyramidal cell layer of CA1 (23%, 29% and 28% decrease, respectively). In CA3, only the CR-positive neuron number decreased (29% decrease). In cortical areas, the number of PV interneurons was reduced in the prefrontal cortex (31% loss) and that of CB interneurons in the entorhinal cortex (50% loss). GAD67 staining was more extensively disrupted. Prefrontal, parietal and piriform cortices showed decreases in GAD67-positive neurons. Moreover, a decrease in these neurons was also recorded in limbic areas including hippocampal CA1 and CA3, and basolateral and median amygdala. Gat-1 staining was similar in both groups. Conclusions: The early lesion of the ventral hippocampus affects inhibitory neurotransmission mainly in limbic regions and specifically in the entorhino-hippocampal loop. However, the reduction observed is not sufficient to lead to spontaneous seizures and is even accompanied by an increase in the threshold to clonic seizures induced by PTZ. Conversely, the threshold to absence-like seizures occurring in the thalamo-cortical loop was decreased in lesioned rats although GABAergic transmission was not affected in these areas