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

Abstract

The 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.

Comparative analysis of primary auditory cortical responses in bats and mice to repetitive stimuli trains

“…Where we saw very clear following responses down the depth of the cortex in bats at a lower (5.28 Hz) and higher (36.76 Hz) frequencies, the following response in mice was noisier and more relegated to thalamic input areas, with separate, repeated granular and infragranular sinks following the stimuli. The noisier signal seen in awake mice was not surprising in comparison with the classically less noisy ketamine-anesthetized signals in mice as well as Mongolian gerbils (Deane et al, 2020, 2022), due to ketamine being a neuronal synchronizer. Interestingly, the awake bat cortical activity was then less noisy compared to these awake rodent datasets (looking more similar to the anesthesia-induced synchrony in data cited above), in the sense of legible sinks far above the baseline cortical activity for each stimulus onset.…”