A spike timing-dependent plasticity rule for single, clustered and distributed dendritic spines

Dendritic spines can undergo structural remodeling, and are the preferential site for the induction of long-term potentiation (LTP) and long-term depression (LTD). In a variant of LTP and LTD, known as spike-timing dependent plasticity (STDP), the sign and magnitude of the change in synaptic strength depends on the timing between the spikes of two connected neurons. Although STDP has been extensively studied in cortical pyramidal neurons, the precise structural organization of excitatory inputs that supports STDP, as well as the structural, molecular and functional properties of dendritic spines during STDP remain unknown. Here we developed a spine STDP protocol, in which two-photon glutamate uncaging over single or multiple spines from the basal dendrites of layer 5 pyramidal neurons, which mimics presynaptic release of glutamate (pre), was paired with somatically generated postsynaptic spikes (post). We found that the induction of STDP in single spines follows a classical Hebbian STDP rule, where pre-post pairings at timings that trigger LTP (t-LTP) produce shrinkage of the activated spine neck and a concomitant increase in its synaptic strength; and post-pre pairings that trigger LTD (t-LTD) decrease synaptic strength without affecting the activated spine shape. Furthermore, we tested whether the single spine-Hebbian STDP rule could be affected by the activation of neighboring (clustered) or distant (distributed) spines. Our results show that the induction of t-LTP in two clustered spines ( 40 μm. These results indicate that the induction of STDP in single, or distributed spines, follow a Hebbian STDP rule. Interestingly, synaptic cooperativity, induced by the co-activation of only two clustered spines and the local spatio-temporal summation of clustered synaptic inputs, provides local dendritic depolarization and local calcium signals that are sufficient to disrupt t-LTD and extend the temporal window for the induction of t-LTP, leading to STDP only encompassing LTP.