Requirement of dendritic calcium spikes for induction of spike‐timing‐dependent synaptic plasticity

Abstract

Spike-timing-dependent synaptic plasticity (STDP) by definition requires the temporal association of pre- and postsynaptic action potentials (APs). Yet, in cortical pyramidal neurons pairing unitary EPSPs with single APs at low frequencies is ineffective at generating plasticity. Using recordings from synaptically coupled layer 5 pyramidal neurons, we show here that high-frequency (200 Hz) postsynaptic AP bursts, rather than single APs, are required for both long-term potentiation (LTP) induction and NMDA channel activation during EPSP-AP pairing at low frequencies. Furthermore, we find that AP bursts can lead to LTP induction and NMDA channel activation during EPSP-AP pairing at both positive and negative times. High-frequency AP bursts generated supralinear calcium signals in basal dendrites suggesting the generation of dendritic calcium spikes, as has been observed previously in apical dendrites during AP burst firing at frequencies greater than 100 Hz. Consistent with a role of these dendritic calcium spikes in LTP induction, pairing EPSPs with low frequency (50 Hz) AP bursts was ineffective in generating LTP. Furthermore, supralinear calcium signals in basal dendrites during AP bursts were blocked by low concentrations of the T- and R-type calcium channel antagonist nickel, which also blocked LTP and NMDA channel activation. These data suggest an important role of dendritic calcium spikes during AP bursts in determining both the efficacy and time window for STDP induction.

Connectivity reflects coding: a model of voltage-based STDP with homeostasis

“…Interestingly, our voltage--based formulation of plasticity, if applied locally in a compartmental model would allow potentiation to occur in a dendritic branch whenever the three conditions: presynaptic activity, recent postsynaptic depolarization, and momentary large depolarization occur together ------ independent of the source of depolarization. Hence, dendritic spikes could lead to potentiation in the absence of somatic action potentials, in agreement with experiments in hippocampal 48--50 and cortical slices 33 .…”

“…3c). Since dendritic spikes which are relevant for burst--timing dependent STDP 33 are broader than somatic action potentials, the 'jumps' in the burst--STDP curves would be blurred.…”

T-type calcium channels in synaptic plasticity

“…Both Ni 2C at low concentration and NMDA receptor antagonists precluded this spike-timing dependent plasticity indicating that the large and long-lasting dendritic depolarization evoked by the T-(R) mediated action potential bursts allows the development of synaptic NMDA currents which contribute to LTP induction. 36,37 The importance of T-(R) burst evoked dendritic spikes for the antidromic propagation of action potentials and the induction of synaptic plasticity was also demonstrated at the synapses between layer 2/3 neurons and layer V pyramidal neurons. Addition of low Ni 2C concentration or intracellular application of QX-314 that blocked action potentials precluded the induction of the LTD evoked when pairing action potential bursts in layer V pyramidal neurons with extracellular synaptic stimulations of layer 2/3 neurons.…”

“…In these dendritic regions which receive the majority of synaptic inputs, 35 the T-(R) bursts lead to a supra-linear increase in intracellular calcium compared to the generation of single action potentials or trains of spikes at lower frequencies. 36,37 Interestingly, at the synapses between layer V pyramidal cells, pairing unitary excitatory postsynaptic potentials (EPSPs) with high-frequency action potential bursts, but not single action potentials, induced a robust LTP. Both Ni 2C at low concentration and NMDA receptor antagonists precluded this spike-timing dependent plasticity indicating that the large and long-lasting dendritic depolarization evoked by the T-(R) mediated action potential bursts allows the development of synaptic NMDA currents which contribute to LTP induction.…”

“…71 As already stated, T-type channels may contribute to this type of plasticity through the backpropagation of action potentials that relieves the magnesium block of synaptic NMDA receptors, resulting in calcium entry through these receptors and a Ca 2C rise in dendritic spines. 36 Recently, the use of transgenic mice has allowed to definitely demonstrate the synergistic contribution of NMDA receptors and T-type channels to LTP in the thalamus. At the glutamatergic synapse between thalamocortical neurons and NRT neurons (Fig.…”