A Spike-Timing Dependent Plasticity Rule for Dendritic Spines

Dendritic spines, the main recipient of excitatory information in the brain, are tiny protrusions with a small head separated from the dendrite by a slender neck. Spines can undergo structural remodeling that is tightly coupled with synaptic function. They are also the preferential site for the induction of long-term potentiation (LTP) and long-term depression (LTD) thought to be the underlying mechanisms for learning and memory in the brain. A variation of LTP and LTD has been described in pyramidal neurons that involve the pairing of pre- and postsynaptic action potentials (APs), known as spike-timing-dependent plasticity (STDP). In this process, the timing between pre- and postsynaptic APs modulates synaptic strength, triggering LTP or LTD.

The sign and magnitude of the change in synaptic strength depend on the relative timing between spikes of two connected neurons (the pre- and postsynaptic neurons). The STDP learning rules have been extracted from studies using connected neuronal pairs or by using extracellular stimulating electrodes, but the precise location and structural organization of the excitatory inputs that support STDP at its minimal functional unit—the dendritic spine—are unknown.

In this talk, Dr. Araya provides evidence showing that the induction of STDP in single or distributed spines from layer 5 (L5) pyramidal neurons follows a bidirectional Hebbian STDP rule. This conclusion is explored using two-photon (2P) glutamate uncaging that mimics synaptic release. Furthermore, he shows that synaptic cooperativity, induced by the co-activation of only two clustered spines using 2P glutamate uncaging, disrupts t-LTD (<40 µm distance between spines) and extends the temporal window for the induction of t-LTP (<5 µm distance between spines). This is due to the generation of differential local N-methyl-D-aspartate (NMDA) receptor-dependent calcium signals, which leads to an STDP rule for clustered inputs only encompassing LTP.

These findings suggest that the functional specificity and structural arrangement of synaptic inputs, distributed or forming micro-clusters in the dendrites of pyramidal neurons, are fundamental for guiding the rules for sensory perception, affecting the STDP learning rule, learning and memory, and ultimately cognition.

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