Kainate Receptor Auxiliary Subunit NETO2-Related Cued Fear Conditioning Impairments Associate with Defects in Amygdala Development and Excitability
eNeuro. 2020-07-01; 7(4): ENEURO.0541-19.2020
DOI: 10.1523/ENEURO.0541-19.2020
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NETO2 is an auxiliary subunit for kainate-type glutamate receptors that mediate normal cued fear expression and extinction. Since the amygdala is critical for these functions, we asked whetherNeto2−/−mice have compromised amygdala function. We measured the abundance of molecular markers of neuronal maturation and plasticity, parvalbumin-positive (PV+), perineuronal net-positive (PNN+), and double positive (PV+PNN+) cells in theNeto2−/−amygdala. We found thatNeto2−/−adult, but not postnatal day (P)23, mice had 7.5% reduction in the fraction of PV+PNN+cells within the total PNN+population, and 23.1% reduction in PV staining intensity compared withNeto2+/+mice, suggesting that PV interneurons in the adultNeto2−/−amygdala remain in an immature state. An immature PV inhibitory network would be predicted to lead to stronger amygdalar excitation. In the amygdala of adultNeto2−/−mice, we identified increased glutamatergic and reduced GABAergic transmission using whole-cell patch-clamp recordings. This was accompanied by increased spine density of thin dendrites in the basal amygdala (BA) compared withNeto2+/+mice, indicating stronger glutamatergic synapses. Moreover, after fear acquisitionNeto2−/−mice had a higher number of c-Fos-positive cells thanNeto2+/+mice in the lateral amygdala (LA), BA, and central amygdala (CE). Altogether, our findings indicate thatNeto2is involved in the maturation of the amygdala PV interneuron network. Our data suggest that this defect, together with other processes influencing amygdala principal neurons, contribute to increased amygdalar excitability, higher fear expression, and delayed extinction in cued fear conditioning, phenotypes that are common in fear-related disorders, including the posttraumatic stress disorder (PTSD).