Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression

• Published in: Nature communications Vol. 6; no. 1; p. 7062
• Main Authors: Bagot, Rosemary C., Parise, Eric M., Peña, Catherine J., Zhang, Hong-Xing, Maze, Ian, Chaudhury, Dipesh, Persaud, Brianna, Cachope, Roger, Bolaños-Guzmán, Carlos A., Cheer, Joseph F., Deisseroth, Karl, Han, Ming-Hu, Nestler, Eric J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.05.2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 631/378/1595/1554; 631/378/2629/1788; 631/378/548; 692/699/476/1414; 82/51; 9/74; Amygdala - physiopathology; Animals; Chronic Disease; Depression - physiopathology; Disease Susceptibility - physiopathology; Gene Expression Regulation; Genes, Immediate-Early; Hippocampus - physiopathology; Humanities and Social Sciences; Long-Term Synaptic Depression; Male; Mice, Inbred C57BL; multidisciplinary; Neurons, Afferent - pathology; Nucleus Accumbens - physiopathology; Prefrontal Cortex; Science; Science (multidisciplinary); Social Behavior; Stress, Psychological - physiopathology; Synapses - metabolism; Synaptic Transmission
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms8062

Enhanced glutamatergic transmission in the nucleus accumbens (NAc), a region critical for reward and motivation, has been implicated in the pathophysiology of depression; however, the afferent source of this increased glutamate tone is not known. The NAc receives glutamatergic inputs from the medial prefrontal cortex (mPFC), ventral hippocampus (vHIP) and basolateral amygdala (AMY). Here, we demonstrate that glutamatergic vHIP afferents to NAc regulate susceptibility to chronic social defeat stress (CSDS). We observe reduced activity in vHIP in mice resilient to CSDS. Furthermore, attenuation of vHIP-NAc transmission by optogenetic induction of long-term depression is pro-resilient, whereas acute enhancement of this input is pro-susceptible. This effect is specific to vHIP afferents to the NAc, as optogenetic stimulation of either mPFC or AMY afferents to the NAc is pro-resilient. These data indicate that vHIP afferents to NAc uniquely regulate susceptibility to CSDS, highlighting an important, novel circuit-specific mechanism in depression. Enhanced glutamatergic transmission in the nucleus accumbens (NAc) has been implicated in the pathophysiology of depression, yet the underlying source is not known. Here, the authors demonstrate a unique role for ventral hippocampal-NAc glutamatergic projections in regulating depression-like behaviour.