Anxiety Cells in a Hippocampal-Hypothalamic Circuit

Abstract

The hippocampus is traditionally thought to transmit contextual information to limbic structures where it acquires valence. Using freely moving calcium imaging and optogenetics, we show that while the dorsal CA1 subregion of the hippocampus is enriched in place cells, ventral CA1 (vCA1) is enriched in anxiety cells that are activated by anxiogenic environments and required for avoidance behavior. Imaging cells defined by their projection target revealed that anxiety cells were enriched in the vCA1 population projecting to the lateral hypothalamic area (LHA) but not to the basal amygdala (BA). Consistent with this selectivity, optogenetic activation of vCA1 terminals in LHA but not BA increased anxiety and avoidance, while activation of terminals in BA but not LHA impaired contextual fear memory. Thus, the hippocampus encodes not only neutral but also valence-related contextual information, and the vCA1-LHA pathway is a direct route by which the hippocampus can rapidly influence innate anxiety behavior.

Input–output organization of the mouse claustrum

“…Interestingly, we found prominent labeling in regions implicated in regulating the arousal and the affective state of the animal, including the basolateral amygdala, CA1 region of the ventral hippocampus, paraventricular (PVT), and reuneins (RE) nuclei of the thalamus, lateral supramammillary nucleus (SUMl), and serotonergic and cholinergic inputs from the dorsal raphe and basal forebrain, respectively (Hu, 2016;Reppucci & Petrovich, 2016;Swanson, 2000;Vertes, Linley, & Hoover, 2015). Many of these regions have been shown to modulate their activity in response to rewarding or aversive stimuli or to cues that predict such outcomes (Beyeler et al, 2018;Burgos-Robles et al, 2017;Hangya, Ranade, Lorenc, & Kepecs, 2015;Jimenez et al, 2018;Matias, Lottem, Dugué, & Mainen, 2017;Zhu, Wienecke, Nachtrab, & Chen, 2016). The CLA may therefore integrate some of these response features and broadcast its output to the cortex to modulate processing under emotionally salient conditions.…”

New neurons restore structural and behavioral abnormalities in a rat model of PTSD

“…Lesion studies (reviewed in Fanselow & Dong, ) and circuit‐based approaches suggest that ventral regions of hippocampus are uniquely involved in anxiety‐like behavior in rodents (Adhikari, Topiwala, & Gordon, ; Felix‐Ortiz & Tye, ). The ventral CA1 region in particular has been implicated in this behavior by the recent finding that this region contains pyramidal neurons that generate anxiety‐like behavior, labeled “anxiety cells”, which are absent in the dorsal portion of CA1 (Jimenez et al, ). Shrinkage of the ventral CA1 has also been implicated in human mood disorders by a recent MRI study showing that women at high risk for depression had decreased hippocampal volume specific to the ventral CA1 region (Durmusoglu et al, ).…”

Chronic activation of the relaxin‐3 receptor on GABA neurons in rat ventral hippocampus promotes anxiety and social avoidance

“…For instance, optogenetic activation of granule cells in the ventral, but not dorsal DG, reduced innate anxiety behavior in mice (Kheirbek et al, 2013). More recent studies using both calcium imaging and optogenetics demonstrated that attenuating the activity of neurons in the ventral CA1 decreased anxiety-like behavior of mice in the EPM, while activation of ventral CA1 neurons projecting to the lateral hypothalamus increased anxiety-like behavior in the open field test (Jimenez et al, 2018). In our current model of RXFP3 action, a presumed inhibition of SST-and PV-interneurons, in the ventral DG and CA1 in particular, increases anxiety-like behavior, consistent with these studies.…”