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

Area of Science:

• Neuroscience
• Cell Biology
• Systems Biology

Background:

• Coherent neuronal activity is crucial for processing stimuli and linking them to perception.
• Presynaptic Cav2.1 voltage-gated calcium channels (VGCCs) orchestrate neuronal stochastic dynamics and neurotransmitter release, influencing synaptic variability.
• The mobile organization of Cav2.1 VGCCs near docked vesicles contributes to synaptic transmission variability.

Purpose of the Study:

• To investigate the role of Cav2.1 VGCC surface motility in primary auditory cortex (A1) input processing in vivo.
• To explore how manipulating VGCC clustering affects neuronal activity and sensory encoding.

Main Methods:

• Utilized a novel optogenetic system with a photo-cross-linkable cryptochrome mutant (CRY2olig) for acute, reversible Cav2.1 VGCC cross-linking.
• Performed laminar current-source density (CSD) recordings in the A1 of transgenic mice with N-terminally citrine-tagged VGCCs.
• Applied varying auditory stimulus sets to map neuronal activity across cortical layers.

Main Results:

• Clustering of Cav2.1 VGCCs significantly suppressed overall sensory-evoked population activity.
• This suppression was particularly pronounced when stimuli induced a highly synchronized distribution of synaptic inputs.
• Demonstrated a direct link between VGCC clustering and the modulation of network activity.

Conclusions:

• The membrane dynamics of presynaptic calcium channels are critical for sensory encoding.
• Cav2.1 VGCC motility dynamically adjusts network activity in response to varying synaptic input strengths.
• Findings underscore the importance of VGCC surface mobility in regulating neural network responses to sensory stimuli.