Chronic social defeat stress (CSDS) is a trauma based paradigm used to model depression- and anxiety-like behavior in rodents. We found previously that CSDS increases glutamatergic synapses on nucleus accumbens (NAc) medium spiny neurons, however the detailed circuitry meditating these effects is unclear. Previous work shows that the NAc receives dense glutamatergic innervation from the intralaminar thalamus (ILT) and prefrontal cortex (PFC). Thus, we analyzed levels of vesicular glutamate transporter 2 (VGLUT2) and VGLUT1, which are predominately found in ILT-NAc or PFC-NAc synapses, respectively. We found increased levels of VGLUT2 in susceptible mice that negatively correlated with social interaction ratio, suggesting that changes in ILT-NAc circuitry may regulate depression- or anxiety-like behavioral phenotypes following CSDS. To establish the functional relevance of these circuits in CSDS-induced depression- or anxiety-like behavior, we utilized circuit specific optogenetic approaches to modulate activity of the ILT-NAc or PFC-NAc. Our results show that rapid activation of the ILT-NAc circuit is both necessary and sufficient for the expression of stress-induced behavior, while rapid stimulation of PFC-NAc circuit had no effect. Interestingly, we also find that the ILT-NAc circuit selectively regulates activity of cholinergic interneurons, which seem to be necessary for the pro-depressant effects of ILT stimulation. In sum, our results identify circuit specific effects of different glutamate inputs wihin the NAc that control depression- or anxiety-like behavioral phenotypes. This provides us with unique insight into how stress impacts NAc circuitry and may inform a greater understanding of the mechanisms by which NAc deep brain stimulation is antidepressant in humans.
Chronic stress induces postsynaptic remodeling of glutamatergic synapses on nucleus accumbens (NAc) medium spiny neurons (MSNs); however, it is unclear which presynaptic glutamate inputs are involved. In this proposal we find evidence of synaptic plasticity within intralaminar thalamus (ILT)-NAc projecting neurons that control depression and anxiety-like behavior.
|Ibi, Daisuke; de la Fuente Revenga, Mario; Kezunovic, Nebojsa et al. (2017) Antipsychotic-induced Hdac2 transcription via NF-?B leads to synaptic and cognitive side effects. Nat Neurosci 20:1247-1259|
|Takahashi, Aki; Chung, Jia-Ru; Zhang, Song et al. (2017) Establishment of a repeated social defeat stress model in female mice. Sci Rep 7:12838|
|Menard, Caroline; Pfau, Madeline L; Hodes, Georgia E et al. (2017) Social stress induces neurovascular pathology promoting depression. Nat Neurosci 20:1752-1760|
|Hodes, Georgia E; Walker, Deena M; Labonté, Benoit et al. (2017) Understanding the epigenetic basis of sex differences in depression. J Neurosci Res 95:692-702|
|Golden, S A; Aleyasin, H; Heins, R et al. (2017) Persistent conditioned place preference to aggression experience in adult male sexually-experienced CD-1 mice. Genes Brain Behav 16:44-55|
|Labonté, Benoit; Engmann, Olivia; Purushothaman, Immanuel et al. (2017) Sex-specific transcriptional signatures in human depression. Nat Med 23:1102-1111|
|Flanigan, Meghan; Aleyasin, Hossein; Takahashi, Aki et al. (2017) An emerging role for the lateral habenula in aggressive behavior. Pharmacol Biochem Behav 162:79-86|
|Jiang, C; Lin, W-J; Sadahiro, M et al. (2017) VGF function in depression and antidepressant efficacy. Mol Psychiatry :|
|Ménard, Caroline; Pfau, Madeline L; Hodes, Georgia E et al. (2017) Immune and Neuroendocrine Mechanisms of Stress Vulnerability and Resilience. Neuropsychopharmacology 42:62-80|
|Chandra, Ramesh; Francis, T Chase; Nam, Hyungwoo et al. (2017) Reduced Slc6a15 in Nucleus Accumbens D2-Neurons Underlies Stress Susceptibility. J Neurosci 37:6527-6538|
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