Postsynaptic burst reactivation of hippocampal neurons enables associative plasticity of temporally discontiguous inputs
Year: 2022
Type: article
Abstract: A fundamental unresolved problem in neuroscience is how the brain associates in memory events that are separated in time. Here, we propose that reactivation-induced synaptic plasticity can solve this problem. Previously, we reported that the reinforcement signal dopamine converts hippocampal spike timing-dependent depression into potentiation during continued synaptic activity (Brzosko et al., 2015). Here, we report that postsynaptic bursts in the presence of dopamine produce input-specific LTP in mouse hippocampal synapses 10 min after they were primed with coincident pre- and post-synaptic activity (post-before-pre pairing; Δt = -20 ms). This priming activity induces synaptic depression and sets an NMDA receptor-dependent silent eligibility trace which, through the cAMP-PKA cascade, is rapidly converted into protein synthesis-dependent synaptic potentiation, mediated by a signaling pathway distinct from that of conventional LTP. This synaptic learning rule was incorporated into a computational model, and we found that it adds specificity to reinforcement learning by controlling memory allocation and enabling both 'instructive' and 'supervised' reinforcement learning. We predicted that this mechanism would make reactivated neurons activate more strongly and carry more spatial information than non-reactivated cells, which was confirmed in freely moving mice performing a reward-based navigation task.
Source: eLife
DOI: 10.7554/elife.81071
Language: English
Topic: Memory and Neural Mechanisms
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: Dopamine-induced hippocampal plasticity: A synaptic model of foraging in mice, Dynamics of protein synthesis in dopamine-dependent hippocampal synaptic plasticity, Retroactive effect of dopamine on hippocampal spike timing-dependent plasticity, Dopamine-induced hippocampal plasticity: A synaptic model of foraging in mice, G265255789, G6289452048, G6657520091, G7069428132
OpenAlex ID: W4304943789