Neural Plasticity in Stress-Related Disorders

Neural plasticity refers to the capacity of the brain to reorganise its structure, function and connectivity in response to experience. In the context of stress-related disorders, plastic changes in key limbic and cortical circuits underlie both adaptive responses and pathological outcomes. Chronic stress typically induces dendritic atrophy and spine loss in the medial prefrontal cortex and hippocampus, impairing cognitive control and emotional regulation. Conversely, stress can enhance synaptic connectivity in the amygdala and nucleus accumbens, potentiating fear learning and anhedonic behaviour. These region-specific alterations are driven by molecular cascades involving dysregulated glucocorticoid signalling, shifts in glutamatergic and GABAergic balance, mitochondrial energy deficits and variations in neurotrophic factors such as brain-derived neurotrophic factor. Crucially, many stress-induced changes are reversible, opening avenues for interventions—from pharmacological agents targeting synaptic receptors to lifestyle and behavioural therapies—that restore neural circuit integrity and resilience.

Research from Nature Portfolio

Recent studies have delineated the role of a claustrum–prelimbic cortex pathway in mediating depression-like responses to chronic social stress. Defeat stress was found to weaken excitatory projections onto parvalbumin interneurons in the prelimbic cortex, releasing pyramidal neurons from inhibition and disrupting local network function. Optogenetic activation or inhibition of this circuit bidirectionally controlled behavioural despair, while chemogenetic modulation of dynorphin/κ-opioid receptor signalling at the claustrum–prelimbic terminals restored network balance and alleviated depressive-like behaviours. This work highlights the precision with which stress reshapes synaptic microcircuits and illustrates circuit-specific targets for therapeutic development.

Neural Plasticity in Stress-Related Disorders publication trend

The graph below shows the total number of articles in neural plasticity in stress-related disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Dendritic spine: A tiny protrusion on a neuron's dendrite that serves as the postsynaptic site for most excitatory synapses.

Synaptic plasticity: The ability of synapses to strengthen or weaken over time in response to patterns of activity or experience.

Long-term potentiation (LTP): A sustained increase in synaptic strength following high-frequency stimulation, regarded as a cellular mechanism for learning and memory.

Glucocorticoids: Steroid hormones released during stress that modulate gene transcription and neuronal function via glucocorticoid receptors.

References

1. The claustrum-prelimbic cortex circuit through dynorphin/κ-opioid receptor signaling underlies depression-like behaviors associated with social stress etiology. Nature Communications (2023).
2. PGAM5 knockout causes depressive‐like behaviors in mice via ATP deficiency in the prefrontal cortex. CNS Neuroscience & Therapeutics (2023).
3. Restorative effect of NitroSynapsin on synaptic plasticity in an animal model of depression. Neuropharmacology (2023).
4. Aging or chronic stress impairs working memory and modulates GABA and glutamate gene expression in prelimbic cortex. Frontiers in Aging Neuroscience (2024).