All-optical functional synaptic connectivity mapping in acute brain slices using the calcium integrator CaMPARI

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• The calcium-modulated photoactivatable ratiometric integrator (CaMPARI) is a genetically encoded sensor.
• CaMPARI allows permanent marking of active cells, facilitating long-term circuit analysis.
• It enables correlation of neural activity with structural or functional labels.

Purpose of the Study:

• To characterize CaMPARI's response to various neuronal calcium signals.
• To evaluate CaMPARI's potential for all-optical functional connectivity mapping.
• To demonstrate CaMPARI's utility in mapping synaptic connectivity in brain slices.

Main Methods:

• Characterization of CaMPARI conversion in mouse acute cortical brain slices.
• Testing CaMPARI response to action potentials and subthreshold synaptic inputs.
• Utilizing optogenetics and CaMPARI for all-optical circuit mapping.

Main Results:

• CaMPARI conversion is triggered by both action potentials and subthreshold synaptic inputs.
• The level of CaMPARI conversion correlates with synaptic strength.
• CaMPARI's conversion rate is tunable and linearly related to light intensity.
• All-optical mapping revealed differential CaMPARI conversion in cortical layers upon thalamic stimulation.

Conclusions:

• CaMPARI provides a tunable, all-optical method for functional circuit mapping.
• It enables the capture of both supra- and subthreshold neuronal activity.
• CaMPARI is a valuable tool for network-wide analysis of neural connectivity.