title: Synaptic plasticity in depression: molecular, cellular and functional correlates.
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. Within subregions of the prefrontal cortex (PFC) and hippocampus structural and synapse-related findings seem consistent with a deficit in long-term potentiation (LTP) and facilitation of long-term depression (LTD), particularly at excitatory pyramidal synapses. Other brain regions are less well-studied; however the amygdala may feature a somewhat opposite synaptic pathology including reduced inhibitory tone. Changes to synaptic plasticity in stress and depression may correlate those to several signal transduction pathways (e.g. NOS-NO, cAMP-PKA, Ras-ERK, PI3K-Akt, GSK-3, mTOR and CREB) and upstream receptors (e.g. NMDAR, TrkB and p75NTR). Deficits in synaptic plasticity may further correlate disrupted brain redox and bioenergetics. Finally, 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.
authors.affiliation: Highclere Court, Woking, Surrey, GU21 2QP, UK. wm_wire@yahoo.co.uk
authors.forename: W N
authors.initials: WN
authors.lastname: Marsden
mesh_terms: D003863:Depression / Q000503:physiopathology* / Q000523:psychology; D004734:Energy Metabolism; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology*; D017397:Prefrontal Cortex / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology; D013315:Stress, Psychological / Q000503:physiopathology* / Q000523:psychology; D013569:Synapses / Q000502:physiology*