Coordinated activation of distinct Ca2+ sources and metabotropic glutamate receptors encodes Hebbian synaptic plasticity

Abstract

At glutamatergic synapses, induction of associative synaptic plasticity requires time-correlated presynaptic and postsynaptic spikes to activate postsynaptic NMDA receptors (NMDARs). The magnitudes of the ensuing Ca2+ transients within dendritic spines are thought to determine the amplitude and direction of synaptic change. In contrast, we show that at mature hippocampal Schaffer collateral synapses the magnitudes of Ca2+ transients during plasticity induction do not match this rule. Indeed, LTP induced by time-correlated pre- and postsynaptic spikes instead requires the sequential activation of NMDARs followed by voltage-sensitive Ca2+ channels within dendritic spines. Furthermore, LTP requires inhibition of SK channels by mGluR1, which removes a negative feedback loop that constitutively regulates NMDARs. Therefore, rather than being controlled simply by the magnitude of the postsynaptic calcium rise, LTP induction requires the coordinated activation of distinct sources of Ca2+ and mGluR1-dependent facilitation of NMDAR function.

Interneuron-specific plasticity at parvalbumin and somatostatin inhibitory synapses onto CA1 pyramidal neurons shapes hippocampal output

“…Important sources of postsynaptic Ca 2+ for the induction of excitatory and inhibitory synaptic plasticity are NMDA receptors and voltage-gated Ca 2+ channels (VGCCs) (Chiu et al, 2018; Griffith et al, 2016; Magee and Johnston, 1997; Tigaret et al, 2016). Since NMDA receptors are blocked in our experiments, we investigated the role of VGCCs in PV-iLTD.…”

Neurotrophin receptor activation rescues cognitive and synaptic abnormalities caused by mutation of the psychiatric risk geneCacna1c

“…2A). TBP mimics neuronal activity patterns observed during learning in vivo (41) and relies on the coordinated activation of postsynaptic NMDAR and VGCCs (27,42). TBP failed to induce LTP at SC-CA1 synapses in slices from Cacna1c +/animals ( Fig.…”

“…Somatic AP broadening in CA1 pyramidal neurons has been proposed to facilitate the dendritic backpropagation of somatic spikes (47) necessary for the induction of associative synaptic plasticity such as TBP-LTP (27,42,44) and to increase the gain of intracellular Ca 2+ signals associated with AP bursts (45) such as those occurring during the exploration of a novel environment (40,48). The reduced AP broadening during burst firing in Cacna1c +/neurons may impact on postsynaptic Ca 2+ signals triggered by APs backpropagated in dendritic spines during plasticity induction.…”

“…Associative learning in the hippocampus is orchestrated by rhythmic neural activity in the entorhinal-hippocampal network and is underpinned by associative synaptic plasticity at hippocampal glutamatergic synapses (22)(23)(24). Induction of plasticity at these synapses relies on the coordinated activation of both postsynaptic NMDA receptors (NMDAR) and voltage-gated calcium channels including L-VGCCs (25)(26)(27).…”

Intracellular calcium stores mediate a synapse-specific form of metaplasticity at hippocampal dendritic spines

“…Ca 2+ release from the IP 3 -sensitive ER store selectively enhances synaptic depression during spike timingdependent plasticity (STDP) We next examine the involvement of ER in spine Ca 2+ dynamics during trains of pre-and postsynaptic action potentials (APs). Experiments on hippocampal as well as cortical synapses suggest that the relative timing of pre-and postsynaptic spiking regulates the activation of NMDAR, and the resulting postsynaptic Ca 2+ elevation directly controls the size and polarity of synaptic changes [57][58][59] . In general, transmitter release preceding (trailing) the arrival of a somatically generated backpropagating action potential (BAP) at the postsynaptic spine is associated with synaptic strengthening (resp.…”