Altered dendritic spine plasticity in a mouse depression model

Abstract

Depressive disorder is a most prevalent psychiatric disorder worldwide and is estimated to be affecting 350 millions of the global population. In the prefrontal cortex (PFC) of depression patients, hypofunction is accompanied with structural deficits, including decreased cell number, neuronal atrophy and decreased number of spine synapses. In rodents, chronic stress exposure induces depressive-like behaviour and results in structural impairment of dendrites of layer 2/3 and 5 pyramidal neurons in PFC, including reduced dendritic spine density and atrophy of apical dendrites. However, it is unclear whether dendritic deficits contribute to depression development. Ketamine, a NMDA receptor blocker, is found to exert rapid, lasting antidepressant effect at a single, sub-anaesthetic dose. Ketamine can also rapidly reverse chronic stress-induced synaptic deficit. Yet, data on the effect of ketamine on dendritic spine plasticity in long-term is lacking. In this study, we used in vivo two-photon transcranial imaging of Thy1-YFP H line mice to investigate dendritic spine plasticity in the chronic restraint stress (CRS) depression model. We found that CRS increased dendritic spine elimination and reduced spine formation of layer V pyramidal neurons in the frontal association cortex. In addition, CRS-induced alterations in spine plasticity precede the onset of behavioural symptoms. Importantly, we found that ketamine treatment counteracted the effects of stress on dendritic spine plasticity. REFERENCES: 1. Duman, R. S., & Aghajanian, G. K. (2012). Synaptic dysfunction in depression: potential therapeutic targets. Science, 338(6103), 68-72. 2. Licznerski, P., & Duman, R. S. (2013). Remodeling of axo-spinous synapses in the pathophysiology and treatment of depression. Neuroscience, 251, 33-50.