- Highclere Court, Woking, Surrey, GU21 2QP, UK
Abstract
Synaptic
plasticity confers environmental adaptability through modification of
the connectivity between neurons and neuronal circuits.
This is achieved
through changes to synapse-associated signaling systems and supported
by complementary changes to cellular morphology and metabolism within
the tripartite synapse.
Mounting evidence suggests region-specific
changes to synaptic form and function occur as a result of chronic
stress and in depression.
The prefrontal cortex (PFC) and hippocampus
represent the best studied regions where functional and structural
findings are consistent with a deficit in long-term potentiation (LTP),
and neuronal and glial growth at excitatory synapses.
Correlating these
changes may be those to glutamate receptors (AMPARs and NMDARs), growth
factor signaling (BDNF-TrkB) and several signal transduction pathways
(NOS-NO, cAMP-PKA, Ras-ERK, PI3K-Akt, GSK-3, mTOR and CREB).
In contrast
other brain regions such as the amygdala may feature a somewhat
opposite synaptic pathology including reduced inhibitory tone.
Deficits
in synaptic plasticity may further correlate disrupted brain redox and
bioenergetics in stress and depression.
Moreover, at a functional level
region-specific changes to synaptic plasticity in depression may relate
to maladapted neurocircuitry and parallel reduced cognitive control over
negative emotion.
