The impact of silencing feed-forward parvalbumin-expressing inhibitory interneurons in the cortico-thalamocortical network on seizure generation and behaviour.

The impact of silencing feed-forward parvalbumin-expressing inhibitory interneurons in the cortico-thalamocortical network on seizure generation and behaviour. Neurobiol Dis. 2019 Sep 05;:104610 Authors: Panthi S, Leitch B Abstract Feed-forward inhibition (FFI) is an essential mechanism within the brain to regulate neuronal firing and prevent runaway excitation. In the cortico-thalamocortical (CTC) network, fast spiking parvalbumin-expressing (PV+) inhibitory interneurons regulate the firing of pyramidal cells in the cortex and relay neurons in the thalamus. PV+ interneuron dysfunction has been implicated in several neurological disorders, including epilepsy. Previously, we demonstrated that loss of excitatory AMPA-receptors, specifically at synapses on PV+ interneuron in CTC feedforward microcircuits, occurs in the stargazer mouse model of absence epilepsy. These mice present with absence seizures characterized by spike and wave discharges (SWDs) on EEG and concomitant behavioural arrest similar to childhood absence epilepsy. The aim of the current study was to investigate the impact of loss of FFI within the CTC on absence seizure generation and behaviour using new Designer Receptor Exclusively Activated by Designer Drug (DREADD) technology. We crossed PV-Cre mice with Cre-dependent hM4Di DREADD strains of mice, which allowed Cre-recombinase-mediated restricted expression of Gi-DREADDs in PV+ interneurons. We then tested the impact...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research