Direct Ventral Hippocampal-Prefrontal Input Is Required for Anxiety-Related Neural Activity and Behavior

Abstract

The ventral hippocampus (vHPC), medial prefrontal cortex (mPFC), and basolateral amygdala (BLA) are each required for the expression of anxiety-like behavior. Yet the role of each individual element of the circuit is unclear. The projection from the vHPC to the mPFC has been implicated in anxiety-related neural synchrony and spatial representations of aversion. The role of this projection was examined using multi-site neural recordings combined with optogenetic terminal inhibition. Inhibition of vHPC input to the mPFC disrupted anxiety and mPFC representations of aversion, and reduced theta synchrony in a pathway-, frequency- and task-specific manner. Moreover, bilateral, but not unilateral inhibition altered physiological correlates of anxiety in the BLA, mimicking a safety-like state. These results reveal a specific role for the vHPC-mPFC projection in anxiety-related behavior and the spatial representation of aversive information within the mPFC.

Hippocampus-driven feed-forward inhibition of the prefrontal cortex mediates relapse of extinguished fear

“…Indeed, an inhibitory influence of the vHPC on mPFC function has been reported to influence the expression of learned fear 38 . However, in contrast to this work, a recent report by Spellman and colleagues suggests that the dominant effect of the vHPC in the mPFC is excitatory 39 . Specifically, they report that optogenetic inhibition of vHPC terminals in the mPFC reduced short-latency (10–20 ms) vHPC-evoked increases in mPFC multiunit activity in anesthetized mice.…”

Anxiolytic effects of muscarinic acetylcholine receptors agonist oxotremorine in chronically stressed rats and related changes in BDNF and FGF2 levels in the hippocampus and prefrontal cortex

“…Several reports support the conclusion that the ventral hippocampus is preferential linked to anxiety-related behaviors (Bannerman et al 2004;Degroot and Treit 2004;Eadie et al 2009;Engin and Treit 2007), while the dorsal hippocampus appears to be subservient to spatial learning and memory (Engin and Treit 2007;Fanselow and Dong 2010;Maurer et al 2005;O'Leary and Cryan 2014;Small et al 2011;Strange et al 2014). In addition, direct ventral hippocampal-medial prefrontal cortex input is required for anxiety-related neural activity and behavior (Padilla-Coreano et al 2016). Overall, the changes of neurotrophic factors found in the ventral hippocampus following CRS correlate with these segregated functions along longitudinal dorsoventral axis of the hippocampus.…”

Limbic modulation of the autonomic nervous system

“…However, evolving evidence implicate other parts of the limbic system such as the ventral hippocampus in processing emotions (Fanselow and Dong, 2010;Snyder et al, 2011;Bannerman et al, 2014;Padilla-Coreano et al, 2016), therefore, it is a potential modulator of motor and autonomic function. Also, following results from simultaneous resting state functional magnetic resonance imaging (fMRI) and heart rate variability assessment in healthy men, Bar et al (2016) hypothesised that there is hippocampal-brainstem connectivity that is responsible for adjusting vagal autonomic activity.…”

“…Certain fields of the hippocampus have been suggested to play crucial roles in the expression of emotions, such as fear, anxiety and stress (Bannerman et al, 2004b;Trivedi and Coover, 2004;Bertoglio et al, 2006;Fanselow and Dong, 2010;Femenia et al, 2012;Ballesteros et al, 2014;Padilla-Coreano et al, 2016), as well as the development of associated disorders, including posttraumatic stress disorder (PTSD) and major depressive disorder (Bonne et al, 2008;Femenia et al, 2012). A common feature in the expression of these emotions is an alteration of basic physiological parameters including respiratory and cardiovascular function, but it is unclear how the hippocampus may be involved in this modulation.…”

“…In a combined experimental approach of multi-site neural recording and optogenetics, Padilla-Coreano et al (2016) showed that inhibition of ventral hippocampus input to the medial prefrontal cortex disrupts the behavioural expression of anxiety. However, studies of this association have given less attention to the involvement of the ventral hippocampus in modulating basic physiological parameters such as respiratory and cardiovascular function (Lockmann et al, 2016).…”