Spatial coupling of Ca2+ entry to Synaptic vesicles required for ultrafast synaptic transmission is not unique to presynaptic CaV2.1 channels

Seminar will be at 301, Samgatha, Nila campus

The central nervous system (CNS) processes information through single units called neurons. The neurons  communicate at a specialized region, synapses between them by releasing chemical messages or neurotransmitters (NTs). At synapses, NTs are stored as pockets called synaptic vesicles (SVs). Upon arrival of information, the  voltage gated calcium channels (VGCCs, that conduct Ca²⁺ inside neuron) at the synapse open. The rapid change  in Ca²⁺ ion concentration inside the neuron is sensed by SVs and they release NTs, and this entire process is called  synaptic transmission. The precise synaptic transmission is governed by VGCCs. In mammalian CNS synapses,  there is family of VGCCs, among them Ca_V2.1, Ca_V2.2 and Ca_V2.3 are highly expressed with Ca_V2.1 being the  most efficient. In addition, the efficiency of synaptic transmission relies on the position of VGCCs to SVs at the  synapse. At many CNS synapses, ultrafast synaptic transmission is Ca_V2.1 exclusive with channels tightly placed  near SVs. Hence, the current paradigm is that ultrafast synaptic transmission is dependent on Ca_V2.1 and not any  other Ca_V2 subtypes. However, it is still unknown if this property is intrinsic to Ca_V2.1. Therefore, to test we  conditionally knocked out (CKO) Ca_V2.1 or both Ca_V2.1/2.2 using either Ca_V2.1^fl/fl mouse or our novel mouse  model, Ca_V2.1^fl/fl/2.2^fl/fl at calyx of held (calyx), an ultrafast auditory brainstem synapse important in sound  localization. We observed a partial compensation of calcium current (I_Ca) in both Ca_V2.1 and Ca_V2.1/2.2 CKO  calyces that highly impacted SV release without altering synapse ultrastructure. More importantly our data  indicated that the compensated channels, predominantly Ca_V2.2 in Ca_V2.1 CKO calyces can still maintain the ultrafast synaptic transmission. The reduction in the SV release could be simply due to reduced I_Ca and Ca_V2.2  biophysical properties. Thus, we propose that the fast SV release is not exclusive to Ca_V2.1 channels.