1 in 6 Americans report a lifetime prevalence of major depressive disorder;however, one-third of depressed patients are resistant to current treatments. The search for more effective pharmacological interventions relies on a better basic science understanding of the pathophysiology underlying mood disorders. The use of animal models, such as chronic social defeat stress, has furthered our understanding of biological mechanisms underlying susceptibility and resilience to stress. Previous studies in our lab showed an increase in excitatory synapses in the nucleus accumbens (NAc), a brain region critical to the reward pathway, in mice susceptible to social defeat. Preliminary data also shows a decrease in inhibitory presynaptic terminals in the NAc following chronic social defeat stress. We hypothesize that downregulation of inhibitory tone in the NAc underlies susceptibility to stress leading to social avoidance behavior. This proposal seeks to more fully examine chronic social defeat stress- induced changes to inhibitory tone in the NAc GABAergic microcircuit and to investigate the contribution of fast- spiking, parvalbumin interneurons to social avoidance behavior.
Major depressive disorder is prevalent in the United States, yet treatment resistance is common and the underlying etiology is unknown. This proposal seeks to examine changes to the inhibitory microcircuit in the nucleus accumbens, a brain region integral to reward processing, after chronic social defeat stress in mice. A better understanding of the pathophysiology of mood and anxiety disorders will promote the development of more effective, targeted therapies.
| Aleyasin, Hossein; Flanigan, Meghan E; Golden, Sam A et al. (2018) Cell-Type-Specific Role of ?FosB in Nucleus Accumbens In Modulating Intermale Aggression. J Neurosci 38:5913-5924 |
| Heshmati, Mitra; Aleyasin, Hossein; Menard, Caroline et al. (2018) Cell-type-specific role for nucleus accumbens neuroligin-2 in depression and stress susceptibility. Proc Natl Acad Sci U S A 115:1111-1116 |
| Golden, Sam A; Heshmati, Mitra; Flanigan, Meghan et al. (2016) Basal forebrain projections to the lateral habenula modulate aggression reward. Nature 534:688-92 |
| Heshmati, Mitra; Golden, Sam A; Pfau, Madeline L et al. (2016) Mefloquine in the nucleus accumbens promotes social avoidance and anxiety-like behavior in mice. Neuropharmacology 101:351-7 |
| Christoffel, Daniel J; Golden, Sam A; Walsh, Jessica J et al. (2015) Excitatory transmission at thalamo-striatal synapses mediates susceptibility to social stress. Nat Neurosci 18:962-4 |
| Hodes, Georgia E; Pfau, Madeline L; Leboeuf, Marylene et al. (2014) Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress. Proc Natl Acad Sci U S A 111:16136-41 |
