Sensorimotor learning and adaptation are key cognitive functions that form the hallmark of biological intelligence. Both processes have long been hypothesized to rely on two critical mechanisms: intrinsic plasticity (IP) within individual neurons and synaptic plasticity (SP) between neurons. Multiple forms of SP have been extensively documented to explain and model experience-dependent re-organization of neural circuits that support learning and memory formation. In contrast, the role of IP – exemplified in spike frequency adaptation and after-hyperpolarization—remains largely unknown. It is believed that SP and IE complement one another, but it remains unclear how, when and under which context each mechanism takes place to facilitate changes at the time scale of behavior. Here, we developed an all-optical approach to independently characterize IP and SP in vivo. We used closed loop activity-dependent optogenetic stimulation, i.e., an optical clamp, in which decoded Calcium fluorescence in real time triggers optogenetic stimulation of target cells to maintain persistent activity states for fixed intervals. We tested this approach applied to excitatory neurons co-expressing the red-shifted opsin (ChRMine) and the genetically encoded calcium indicator (GCaMP7s) under variable optical clamp thresholds. We found that the interstimulation interval – a measure of how neurons would remember repeated inputs leading to a persistent activity state – was a function of the activity threshold chosen, and eventually converged to a steady state value, suggesting it is an intrinsic cellular property. Our results suggest a novel approach to probe IP of single cells independent of changes induced by SP in awake behaving animals.