Review Article

The Role of Neural Plasticity in Depression: From Hippocampus to Prefrontal Cortex

Table 1

Changes of neural plasticity induced by depression in various brain regions.

Brain regionChanges of neural plasticityMechanisms

HippocampusSynaptic plasticity (1) Impairment of LTP in CA3
(2) Facilitation of LTD and tLTD in CA1
(3) Downregulation of synaptic proteins and growth factors
Volumetric changes (1) Disruption and atrophy of neurons and glia
(2) Neurodegenerative reaction to high levels of glucocorticoid
Neurogenesis (1) Hindered by high levels of glucocorticoids and enhanced by adrenalectomy
(2) Additive effects in mice, while reduced in humans
(3) Additive function in the circuitry
Apoptosis (1) Depression promotes apoptosis in the hippocampus
(2) The effects caused by chronic depression last longer than those of acute depression

Prefrontal cortexSynaptic plasticity (1) Disturb expression of NMDA receptor gene
(2) Downregulation of proteins for the GABAergic synapses, dopaminergic synapses, synaptic vesicle cycle
(3) Downregulation of mRNA and protein levels of glutamate transporter SLC1A1
Activity in vmPFC and
dlPFC 
(1) Hyperactivity in vmPFC and hypoactivity in dlPFC during progression of depression; hyperactivity in dlPFC and hypoactivity in vmPFC during recovery phase
(2) Decrease of cortical thickness of right vmPFC through disruption and atrophy of neurons and glia
Energetic metabolism (1) Reduction of glutamate in the GABAergic pathway
(2) Activation of metabotropic glutamate receptor 3
(3) Disturbed expression of NMDA receptor gene
(4) Downregulation mRNA and protein levels of glutamate transporter SLC1A1
Hemodynamic responses (1) Lack of activation of oxygenated hemoglobin
(2) Changes in hemoglobin concentration may be positively correlated with severity of depression

AmygdalaSynaptic plasticity (1) Increased expression of BDNF
(2) Disrupted glutamate signaling at the NMDA receptor
(3) Neonatal glucocorticoid treatment enhances LTP response
Volumetric changes(1) Larger gray matter volume in the bilateral amygdala
Functional connectivity (1) Decreased bilateral amygdala-right insular cortex connectivity
(2) In the left amygdala, the functional connectivity decreased in positive network and increased in negative network
(3) Amygdala-associated brain circuits may change with depression severity
(4) Prenatal maternal depression increases functional connectivity in infants

Ventral striatum(1) Caused long-term adaptations in the ventral tegmental area-accumbens pathway
(2) -Adrenoceptor dependent downregulation of the membrane GluR1 subunit
(3) Decreased dendritic length, branching, spine density on medium spiny neurons in the nucleus accumbens shell

HypothalamusSynaptic plasticity(1) Increased mRNA expression of
synaptotagmin I and synapsin I