This abstract has been invited to present during the Investigators Workshop Platform poster session
Rationale: Psychiatric disorders, including depression and anxiety, are comorbid in up to 75% of patients with epilepsy, negatively impacting their quality of life. While comorbid depression and epilepsy has received considerable attention, less has been paid to comorbid anxiety, despite the higher incidence rate and equally debilitating effects. While mechanisms linking epilepsy with comorbid anxiety are unclear, research implicates the amygdala in the network communication of anxiety and fear. Parvalbumin (PV) interneurons play a critical role in both the generation of network oscillations and control over networks governing the behavioral expression of fear and anxiety.1 Interestingly, preliminary evidence shows a loss of PV immunoreactive neurons, well described in the hippocampus of chronically epileptic mice, occurs in the basolateral amygdala (BLA) as well.Despite interneuron vulnerability to chronic epilepsy and the role of PV interneurons in regulating network communication, little is known of the impact of epilepsy on the network communication of anxiety. Therefore, we hypothesize that chronic epilepsy results in the loss of PV expressing interneurons in the BLA, resulting in pathological changes which impair the network communication of safety2 leading to the development of comorbid anxiety in chronically epileptic mice. Methods: A recently described chemogenic seizure model using ventral intrahippocampal injection of kainic acid (vIHKA) recapitulates pathologies associated with the dorsal IHKA model, in addition to affective phenotypes associated with depression and anxiety.3 We will utilize this model in combination with whole-cell patch clamp electrophysiology, in vivo, and ex vivo local field potential (LFP) recordings in vIHKA and control mice to determine the effects of chronic epilepsy on principal neurons and PV interneurons within the BLA. Using programmatic analysis of single cell electrophysiological recordings, we determine intrinsic properties of BLA principle cells and PV interneurons including input-output, rheobase, resonance, and frequency and amplitude of spontaneous synaptic properties. To compare network communication within the BLA between chronically epileptic and control mice, in vivo and ex vivo LFP recordings are analyzed for peak oscillation frequency, power-area, and power-spectral density. Results: The vIHKA model of temporal lobe epilepsy displays hallmarks of anxiety-like behavior and exhibits a significant loss of PV-immunoreactive neurons within the BLA. PV interneurons following vIHKA injection exhibit decreased excitability. Changes in firing characteristics and synaptic properties of principal cells and PV interneurons remaining following vIHKA-induced cell loss, and local oscillatory network activity may underlie the corruption of network communication of anxiety following chronic epilepsy. Conclusions: Our data in chronically epileptic mice indicate a loss of PV interneurons in the BLA, and impaired network communication of anxiety in vIHKA mice compared to controls. Corruption of oscillatory network activity within the BLA may underlie the increase in anxiety like behaviors in chronically epileptic mice. Characterizing the effects of compromised inhibition in the BLA of chronically epileptic mice will enhance our understanding of anxiety comorbidity with epilepsy.
Stujenske et al.Neuron83, 919–933 (2014).
Davis et al.Nat Neurosci20, 1624–1633 (2017).
Zeidler, et al.eNeuro5, 0158–18 (2018).
Funding: Please list any funding that was received in support of this abstract.: This work was supported by R01NS105628, and R01NS102937.