July Newsletter: Rho-family GTPases, Neuronal Plasticity, and Depression

Depression constitutes a spectra of symptoms that adversely affect an individual’s cognitive, emotional, motivational, and physiological well-being; this collection of heterogenous symptoms and pathologies is termed major depressive disorder (MDD), and for as many as 40% of individuals suffering from MDD, medications are not able to provide sufficient and/or long-lasting therapeutic relief1,2. Functional imaging studies and neuropathological studies with post-mortem human brains implicate dysfunction in the nucleus accumbens (NAc) and ventral tegmental area (VTA), critical nuclei in the brain’s dopaminergic (DAergic) reward pathways2-6. The VTA consists of a major population of DA neurons which primarily innervates the NAc2,5. Dysfunctional neurophysiology and plasticity in these nuclei likely contribute to some of the symptoms of MDD, specifically loss of pleasure and motivation (anhedonia)2-6. Anhedonia is studied using chronic social defeat stress (CSDS) which elicits depression-associated behaviors (e.g., reduced social interactions, increased anhedonia, negative body weight changes) in 70% of mice (i.e., termed stress-susceptible) while the remaining 30% do not undergo these adverse behavioral changes (i.e., termed stress-resilient)2,7.

The structure and function of DAergic neurons in VTA and the DA receptor 1 (D1R)- and D2R-expressing NAc neurons are remodeled during CSDS2,8-16. Stress-induced anhedonia to model depression-like behavior results in reduced spontaneous excitatory inputs to D1R-expressing MSNs, whereas D2R-expressing MSNs undergo the opposite change17,18. D1R-expressing (but not D2R) accumbal neurons also display reduced dendritic arborization (morphological plasticity), an important parameter in excitatory neurotransmission for the MSNs as dendritic spines are the primary site of excitatory synapses8,10-12,19,20.

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 Also included in this newsletter:

  • Tubulin and Actin Live Cell Reagents, G-LISA Activation Assay Kits, Tubulin Kits, Actin Biochem Kits
  • Related Publications