AbstractIn reward-based learning, synaptic eligibility traces are a well-defined theoretical solution for the conversion of initial co-activation of pre and postsynaptic neurons into long-term changes in synaptic strength by reward-linked neuromodulators. However, the types of neuromodulators involved in such a phenomenon in mouse visual cortex remain unknown. To characterize the Ex vivo condition, we used optogenetic stimulation of channelrhodopsin-(ChR2) expressing Cre/Ai32(ChR2-eYFP); Tph2-Cre/Ai32(ChR2-eYFP); Thi-Cre/Ai32(ChR2-eYFP) homozygous mice, which release acetylcholine, serotonin, and norepinephrine, respectively. With these mice it is possible to measure the transformation of eligibility traces into long-term changes by endogenous neuromodulators. Here we delineated that layer 2/3 neurons in the visual cortex showed no LTD after conditioning with paired-pulse low-frequency stimulation (ppLFS; 2Hz, 15 min). However, if conditioning was paired with acetylcholine, serotonin, or norepinephrine release upon 473 nm optical stimulation in brain slices, LTD occurs in every case. Thus, our data suggests a new pathway to connect the gap between stimulus and reward. Moreover, we found that stimulation by theta-glass or metal stimulators evoked IPSC traces with the same amplitudes but differences in decay kinetics, further questioning the appropriate use of stimulators in brain slices for evoking an event.
NMDAR-independent acetylcholine, serotonin, and norepinephrine mediated modulation of synaptic eligibility traces into LTD in mice visual cortex
