Inhibiting presynaptic calcium channel mobility in the auditory cortex suppresses synchronized input processing

Abstract

AbstractThe emergent coherent population activity from thousands of stochastic neurons in the brain is believed to constitute a key neuronal mechanism for salient processing of external stimuli and its link to internal states like attention and perception. In the sensory cortex, functional cell assemblies are formed by recurrent excitation and inhibitory influences. The stochastic dynamics of each cell involved is largely orchestrated by presynaptic CAV2.1 voltage-gated calcium channels (VGCCs). Cav2.1 VGCCs initiate the release of neurotransmitters from the presynaptic compartment and are therefore able to add variability into synaptic transmission which can be partly explained by their mobile organization around docked vesicles. To investigate the relevance of Cav2.1 channel surface mobility for the input processing in the primary auditory cortex (A1) in vivo, we make use of a new optogenetic system which allows us to acutely cross-link Cav2.1 VGCCs via a photo-cross-linkable cryptochrome mutant, CRY2olig. In order to map neuronal activity across all cortical layers of the A1, we performed laminar current-source density (CSD) recordings with varying auditory stimulus sets in transgenic mice with a citrine tag on the N-terminus of the VGCCs. Clustering VGCCs suppresses overall sensory-evoked population activity, particularly when stimuli lead to a highly synchronized distribution of synaptic inputs. Our findings reveal the importance of membrane dynamics of presynaptic calcium channels for sensory encoding by dynamically adjusting network activity across a wide range of synaptic input strength.Statement of SignificanceVoltage Gated Calcium Channel (VGCC) mobility plays an important role in neuronal firing dynamics. Failure of these channels to function or be regulated has been linked to migraine and ataxia. We here link the microscopic process of VGCC mobility to the mesoscopic population dynamics as a mechanism to regulate and appropriately amplify synaptic inputs of different strengths to the mouse primary auditory cortex. We also demonstrate a novel and effective technique with which VGCC function can be further explored in meso- or macroscopic scales and with behaving subjects. We believe that this is of importance to the broader scientific community in aspects of non-linear scaling in the brain, potential translational applications, and basic research on cortical mechanisms of physiological function.