Selective photostimulation of locus coeruleus terminals in hippocampal-CA1 induces LTP and enhances spatial memory in...

Long-term potentiation (LTP) represents a fundamental form of synaptic plasticity that underlies long-term memory. Catecholaminergic projections from the locus coeruleus (LC) to the hippocampal CA1 region modulate spatial memory consolidation; however, it remains unclear whether activity in this pathway directly induces in vivo synaptic potentiation. The present study demonstrates that selective photostimulation of tyrosine hydroxylase-positive (TH⁺) LC axon terminals in CA1 induces robust optogenetic LTP (oLTP) in the Schaffer collateral pathway. Induction of oLTP is associated with increased extracellular concentrations of noradrenaline, dopamine, and glutamate in CA1, and is abolished by local blockade of β-adrenergic, D1 dopamine, or NMDA receptors. In awake, freely moving mice, post-training induction of oLTP enhances consolidation of weak object-location memories and promotes long-term persistence of spatial memory in the Morris water maze and Barnes maze for up to 10 days. These findings establish a causal relationship between LC-derived catecholaminergic input, in vivo hippocampal LTP induction, and durable spatial memory, and identify a circuit-specific neuromodulatory mechanism that regulates synaptic plasticity during memory consolidation.