A novel, complex-spike burst-dependent form of BCM-like metaplasticity regulates the induction of behavioral timescale synaptic plasticity

The induction of Hebbian LTP can produce a persistent, heterosynaptic suppression of LTP induction at other synapses. This form of metaplasticity, originally formalized in the Bienenstock, Cooper, and Munro (BCM) plasticity rule, generates competitive interactions between synapses and is thought to support sparse information encoding during memory formation. Importantly, although a non-Hebbian, burst-dependent form of synaptic plasticity known as behavioral timescale plasticity (BTSP) is essential for hippocampal memory encoding, little is known about the role of metaplasticity in BTSP. Thus, I examined whether the induction of BTSP at one set of synapses in the CA1 region of mouse hippocampal slices alters plasticity at other synapses. I find that the induction of BTSP by EPSP-evoked complex-spike (CS) bursts triggers a robust, but transient, heterosynaptic depression of excitatory synaptic transmission. This depression is induced by postsynaptic CS bursts, requires activation of L-type Ca2+ channels, and is mediated by activation of A1-type adenosine receptors. Notably, the heterosynaptic depression triggered by the induction of BTSP generates a CS burst-dependent form of BCM-like metaplasticity that transiently suppresses the induction of BTSP at other synapses. Together, these results provide experimental support for computational predictions that burst-dependent forms of plasticity are constrained by a distinct, burst-dependent form of BCM metaplasticity, and identify a mechanism that may contribute to sparse memory encoding during BTSP induction.