Progress in Neuro-Psychopharmacology and Biological Psychiatry
22 December 2012
- Highclere Court, Woking, Surrey, GU21 2QP, UK
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.