Title:Synaptic Plasticity, Metaplasticity and Depression
Volume: 15
Issue: 1
Author(s): Linnea R. Vose and Patric K. Stanton
Affiliation:
Keywords:
Depression, glutamate, metaplasticity, mGluR, NMDAR, synaptic plasticity.
Abstract: The development of a persistent depressive affective state has for some
time been thought to result from persistent alterations in neurotransmitter-mediated
synaptic transmission. While the identity of those transmitters has changed over the
years, the literature has lacked mechanistic connections between the neurophysiological
mechanisms they regulate, and how these mechanisms alter neuronal function, and,
hence, affective homeostasis. This review will examine recent work that suggests that
both long-term activity-dependent changes in synaptic strength (“plasticity”), and shifting
set points for the ease of induction of future long-term changes (“metaplasticity”),
may be critical to establishing and reversing a depressive behavioral state. Activitydependent
long-term synaptic plasticity involves both strengthening and weakening
of synaptic connections associated with a dizzying array of neurochemical alterations that include
synaptic insertion and removal of a number of subtypes of AMPA, NMDA and metabotropic glutamate
receptors, changes in presynaptic glutamate release, and structural changes in dendritic spines. Cellular
mechanisms of metaplasticity are far less well understood. Here, we will review the growing evidence
that long-term synaptic changes in glutamatergic transmission, in brain regions that regulate mood, are
key determinants of affective homeostasis and therapeutic targets with immense potential for drug
development.
