Loss of PV Interneurons in the BLA May Contribute to Altered Network and Behavioral States in Chronically Epileptic Mice.

Psychiatric disorders, including anxiety and depression, are highly comorbid in people with epilepsy. However, the mechanisms mediating the shared pathophysiology are currently unknown. There is considerable evidence implicating the basolateral amygdala (BLA) in the network communication of anxiety and fear, a process demonstrated to involve parvalbumin-positive (PV) interneurons. The loss of PV interneurons has been well described in the hippocampus of chronically epileptic mice and in postmortem human tissue of patients with temporal lobe epilepsy (TLE). We hypothesize that a loss of PV interneurons in the BLA may contribute to comorbid mood disorders in epilepsy. To test this hypothesis, we employed a ventral intrahippocampal kainic acid model of TLE in mice, which exhibits profound behavioral deficits associated with chronic epilepsy. We demonstrate a loss of PV interneurons and dysfunction of the remaining PV interneurons in the BLA of chronically epileptic mice. Furthermore, we demonstrate altered principal neuron function and impaired coordination of BLA network and behavioral states in chronically epileptic mice. To determine whether the loss of PV interneurons contributes to these altered network and behavioral states, we partially ablated PV interneurons in the BLA by stereotaxically injecting AAV-Flex-DTA into the BLA of PV-Cre mice. Loss of PV interneurons in the BLA is sufficient to alter behavioral states, such as increasing avoidance behaviors and impairing fear learning. These data suggest that compromised inhibition in the BLA in chronically epileptic mice may contribute to behavioral deficits, suggesting a novel mechanism contributing to comorbid anxiety and epilepsy.