Memory allocation to long-term potentiation-induced synapses

Abstract

Where memory is physically stored in the brain has been a challenging question for Neuroscience of learning and memory. Recent studies reveal that memory within a brain region is allocated to specific subset of neurons with relatively high level of CREB or excitability. By contrast with such neuronal allocation, synaptic-level allocation has been unknown. In this thesis, I show that using optogenetic manipulation of auditory inputs to the lateral amygdala, long-term potentiation (LTP) of the auditory synapses directs memory allocation to the synapses. During auditory fear conditioning, I delivered 10-Hz optogenetic stimulation at the auditory synapses immediately before the tone presentation, which enables induction of LTP at the synapses. Lack of the stimulation during conditioning, however, LTP at those synapses was not induced. Reactivation of the LTP synapses successfully induced rear memory recall, whereas inactivation of LTP synapses prevents fear memory recall even during presentation of the tone and the optogenetic stimulation. Furthermore, optogenetic reactivation of the LTP synapses made the memory reconsolidation-like labile state of auditory fear memory. Finally, long-term depression (LTD) of the LTP synapses at 6 hour after the training disrupted auditory fear memory persistently, whereas LTD at 2 minutes after the training did not. Altogether, these findings reveal that auditory fear memory allocates to the late-phase LTP (L-LTP)-induced synapses and propose that the synaptic memory allocation is composed of two-step "tagging and allocation" model, like "synaptic tag and capture" model of LTP in vitro.