DENDRITIC INTEGRATION UNDER CONTROLLED EXCITATION-INHIBITION BALANCE

The investigation of neuronal input-output function has traditionally relied on in vitro experimental paradigms, which provide precise control and high efficiency. However, this approach faces a fundamental trade-off: neurons recorded from slice preparations lack the intense excitatory and inhibitory synaptic inputs characteristic of in vivo network activity. Consequently, neurons remain in a quiescent, low-conductance state that does not fully reflect their physiological behavior in the brain.
To bridge this gap, we developed optical clamping to generate synaptic conductance patterns over the entire dendritic tree, resembling an in vivo high-conductance state. Using two-color optogenetics and two spatial light modulators, we independently control excitation and inhibition to recreate physiologically realistic synaptic drive. Combined with microiontophoresis and pharmacological manipulations, optical clamping enables controlled interrogation of NMDAR-dependent nonlinearities that shape dendritic integration during emulated network activity.