β‐Adrenergic Receptor Activation Modulates the Induction of Complex Spike‐Dependent LTP by Regulating Multiple Forms of Heterosynaptic Plasticity

Norepinephrine, acting through β‐adrenergic receptors (β‐ARs), has a key role in hippocampus‐dependent forms of learning. Although β‐AR activation also facilitates the induction of Hebbian LTP, recent findings indicate that a non‐Hebbian form of synaptic plasticity, known as behavioral timescale synaptic plasticity (BTSP), underlies hippocampus‐dependent spatial learning. To explore the role of noradrenergic signaling in BTSP, I investigated the effects of the β‐AR activation on complex spike (CS) burst‐dependent LTP, a form of BTSP induced by theta‐pulse stimulation (TPS) protocols in the CA1 region of mouse hippocampal slices. β‐AR activation not only enhanced the homosynaptic potentiation of synaptic transmission induced by TPS but also modulated heterosynaptic forms of plasticity critical for CS burst‐dependent LTP induction. Specifically, β‐AR activation enhanced the heterosynaptic facilitation of CS bursting induced by brief TPS trains and facilitated the ability of synapses to interact in a cooperative fashion to undergo LTP, even when independent groups of synapses were activated up to 10 s apart. β‐AR activation also enhanced a CS burst‐dependent form of heterosynaptic depression elicited by longer trains of TPS, resulting in a winner‐take‐all form of synaptic competition where the β‐AR‐mediated facilitation of LTP induction at one group of synapses was associated with a strong, heterosynaptic suppression of LTP at other synapses. Together, these findings indicate that β‐AR activation dynamically regulates fundamental properties of CS burst‐dependent synaptic plasticity by modulating multiple forms of heterosynaptic plasticity.