Quantitative analysis of axonal Ca2+ channels in cortical GABAergic neurons

PD Dr. Akos Kulik (Institute of Physiology II)

In cortical networks, a heterogeneous set of inhibitory GABAergic interneurons regulate the complex interactions among principal cells including population oscillations. The perisomatic targeting fast-spiking parvalbumin-expressing (PV+) and the regular-spiking cholecystokinin-expressing (CCK+) cells control the output most notably the synchrony of action potentials of large cell populations: the PV+ cells represent a non-plastic clockwork that operates the machinery of principal cell ensembles and synchronizes their activity, whereas CCK+ cells appear to be the fine-tuning devices. The highly specialized function of these interneurons is critically based on the fine control of transmitter release that requires appropriate axonal distribution and functional coupling of high voltage-activated Ca²⁺ (Ca_v) channels and neurotransmitter receptors. Therefore, we have been studying the subcellular location of the Ca_v2.1, Ca_v2.2, and Ca_v2.3 Ca²⁺ channels, which conduct P/Q-type, N-type, and R-type Ca²⁺ currents, respectively in synaptic and extrasynaptic membranes of boutons of PV+ and CCK+ cells, as well as the dynamic regulation of their surface expression in response to metabotropic receptor (GABA_BR, mGluR) activation using a combination of high-resolution SDS-FRL immunoelectron microscopic and pharmacological approach.