Cortical plasticity induced by conversion of synaptic eligibility traces in vivo

摘要

Cortical plasticity induced by conversion of synaptic eligibility traces in vivo Our brain has the ability to learn about rewarding sensory stimuli through synaptic modifications of the associated circuits (reward-based learning). These changes depend on the sensory stimuli and the associated reward which is typically delayed. This temporal difference creates a conundrum, the so called “distal reward problem”: How does the brain know which synapses are responsible for the reward among those that were active during the waiting period? A theoretical solution is ‘synaptic eligibility traces,’ silent and transient synaptic tags that can be converted into long-term synaptic strength changes by reward-linked neuromod- ulators. Previously in visual cortical slice preparation, we showed distinct synaptic eligibility traces for long-term potentiation (LTP) and depression (LTD), which are transformed by retrograde nore- pinephrine and serotonin signals, respectively. In the present work, we show evidence demonstrating the functional role of synaptic eligibility traces in the plasticity of visual responses in vivo using whole cell patch clamp recording and optical imaging of the intrin- sic cortical signal. First, optogenetic activation of norepinephrine or serotonin projections in a temporally retrograde manner induced rapid and selective potentiation or depression of the associated visual response, respectively. Secondly, interfering with the con- version of synaptic eligibility traces prevented the rapid change of visual response by neuromodulators. Furthermore, we tested these ideas in a more “natural” setting, and found that preventing the conversion of eligibility traces also prevented ocular dominance changes induced by monocular deprivation. These results suggest that the conversion of synaptic eligibility traces by neuromodu- lators has a functional role in visual cortical plasticity via reward based learning mechanisms.