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A Spike-Timing Dependent Plasticity Rule for Dendritic Spines

presented by: Dr. Roberto Araya, the CHU Sainte-Justine Research Centre and University of Montreal

During this presentation, you will learn how the application of multiphoton glutamate uncaging to mimic synaptic release helped to decipher the mechanisms of dependence of spike-timing dependent plasticity on location and structural organization of spines in pyramidal cells of cortical layer 5. With this approach, it was found that spike-timing dependent plasticity that governs learning, memory, and ultimately cognition, follows a bidirectional Hebbian rule.

Dr. Araya's Abstract

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 and are 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 neuron). 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 excitatory inputs that support STDP at its minimal functional unit—the dendritic spine—are unknown.

In this talk, Dr. Araya will provide evidence showing that the induction of STDP in single or distributed spines from layer 5 (L5) pyramidal neurons using two-photon (2P) glutamate uncaging, to mimic synaptic release, follows a bidirectional Hebbian STDP rule. Furthermore, he will show 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) via the generation of differential local N-methyl-D-aspartate (NMDA) receptor-dependent calcium signals, leading 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.


Dr. Roberto Araya

CHU Sainte-Justine Research Centre and University of Montreal

Dr. Araya completed his graduate studies with a joint thesis at the Catholic University in Chile and the University of Bonn in Germany. For his post-doctoral training, Dr. Araya joined the laboratory of Dr. Rafael Yuste at Columbia University. He was funded by a Latin American PEW fellow in biomedical sciences and later by the Howard Hughes Medical Institute. In 2011, he was hired in the Department of Neuroscience at the University of Montreal. Dr. Araya recently joined the CHU Sainte-Justine Research Centre as an Associate Professor to form part of the Child and Brain Development research axis, with the goal to further establish collaborations and pursue translational work in autism spectrum disorders. His research is well funded by the Canadian Institute of Health Research and other institutions and foundations.

Dr. Araya's research focuses on understanding how neocortical pyramidal neurons, and the circuitry they reside in, enables sensory processing. More specifically, Dr. Araya is passionate about dendritic computations, and how dendritic spines control the processing, storage, and integration of synaptic inputs. He is extending these questions to neurological disorders to uncover abnormal neuronal and circuit elements via a multifaceted approach that includes a state-of-the-art custom-built in vivo and in vitro two-photon setup with holographic stimulation capabilities and electrophysiological, structural, genetic, and molecular tools.