N-type calcium channels control GABAergic transmission in brain areas related to fear and anxiety

Abstract

Presynaptic N-type (CaV2.2) calcium channels are key for action potential evoked transmitter release in the peripheral and central nervous system. Previous studies have highlighted the functional relevance of N-type calcium channels at both the peripheral and central level. In the periphery, the N-type calcium channels regulate nociceptive and sympathetic responses. At the central level, N-type calcium channels have been linked to aggression, hyperlocomotion, and anxiety. Among the areas of the brain that are involved in anxiety are the basolateral amygdala, medial prefrontal cortex, and ventral hippocampus. These three areas share similar characteristics in their neuronal circuitry. Pyramidal projection neurons are under the inhibitory control of a wide array of interneurons including those that express the peptide cholecystokinin. This type of interneuron is well-known to rely on Ntype calcium channels to release GABA in the hippocampus, however whether these channels control GABA release from cholecystokinin-expressing interneurons in the basolateral amygdala and medial prefrontal cortex is not known. Here using sophisticated mouse models to genetically label cholecystokinin-expressing interneurons, we found that N-type calcium channels control ~50% of GABA release in basolateral amygdala. By contrast, N-type calcium channels are functionally absent in synapses of cholecystokinin-expressing interneurons of medial prefrontal cortex. Our findings provide insights into the precise localization of N-type calcium channels in synapses of brain areas related to anxiety.