Gina Turrigiano, PhD
Professor of Biology
Volen National Center for Complex Systems
Brandeis University

The Self-Tuning Neuron: Homeostatic Plasticity of Neocortical Synapses

Many developing circuits require experience, in the form of ongoing patterned activity, to become fully functional. Identifying the cellular plasticity mechanisms that underlie this refinement is critical for understanding the role of early experience in normal and abnormal development. Until recently the field had largely concentrated on the role of rapid, synapse-specific forms of synaptic plasticity such as long-term potentiation (LTP) and depression (LTD). However, theoretical considerations suggest that such "Hebbian" forms of plasticity are highly unstable and cannot function efficiently without complementary forms of plasticity that stabilize neuronal and network tiring properties. Over the past decade a body of work has identified synaptic scaling, a form of homeostatic synaptic plasticity, as a critical mechanism that provides stability to developing neurons and circuits. This form of plasticity scales neuronal synaptic strengths up or down in the right direction to stabilize firing and appears to operate on the entire distribution of a neuron's synaptic weights. In addition to stabilizing Hebbian plasticity, synaptic scaling likely plays an important role in balancing excitation and inhibition within highly recurrent cortical microcircuits.

Dr. Turrigiano began by discussing the expression mechanism(s) of synaptic scaling at excitatory synapses, with a focus on the role of postsynaptic changes in glutamate receptor accumulation. She contrasted the molecular expression mechanisms of synaptic scaling with those underlying LTP and suggested that there are several pathways for regulating receptor accumulation that operate over different temporal and spatial scales. She then turned to a discussion of the induction mechanism and the role of presynaptic vs. postsynaptic firing in generating a signal for synaptic scaling. Her data suggest that synaptic scaling is a function of postsynaptic firing and is a mechanism that allows neurons to sense their own activity and adjust synaptic strengths to keep this activity relatively constant.