Hypothalamus pathway drives defense behaviors

Summary: A newly discovered pathway that links the hypothalamus and midbrain drives innate defense behaviors. The findings could have implications for developing therapies for anxiety disorders.

Source: SfN

Scientists have identified a previously unknown pathway connecting the hypothalamus and midbrain that drives defensive behaviors, according to research in mice published in eNeuro. Further research on this pathway could increase understanding of anxiety disorders.

The paraventricular hypothalamus has been shown to play a role in maintaining body states, but it was not known if it directly caused defensive behaviors. To investigate this, Qingchun Tong and colleagues at the University of Texas Health Science Center at Houston developed a mouse model with hypothalamus neurons that could be stimulated with light.

Using synapse markers, they found that these neurons were connected to the midbrain and when stimulated caused defensive behaviors such as grooming and escape jumping.

This shows the hypothalamus
Heat maps of mice activity. Stimulating the hypothalamus neurons (center) caused increased avoidance of the light-on region, which is a defense behavior. The image is credited to Mangier et al., eNeuro 2019.

This hypothalamus-midbrain circuit drives innate defensive behaviors, which can go awry in anxiety. Further research on dysfunctions in this or other defense pathways could reveal mechanisms for generalized anxiety disorders.

About this neuroscience research article

Media Contacts:
Calli McMurray – SfN
Image Source:
The image is credited to Mangier et al., eNeuro 2019.

Original Research: Closed access
“Defensive Behaviors Driven by a Hypothalamic-Ventral Midbrain Circuit”. Leandra R. Mangieri, Zhiying Jiang, Yungang Lu, Yuanzhong Xu, Ryan M. Cassidy, Nicholas Justice, Yong Xu, Benjamin R Arenkiel and Qingchun Tong.
eNeuro. doi:10.1523/ENEURO.0156-19.2019


Defensive Behaviors Driven by a Hypothalamic-Ventral Midbrain Circuit

The paraventricular hypothalamus (PVH) regulates stress, feeding behaviors and other homeostatic processes, but whether PVH also drives defensive states remains unknown. Here we showed that photostimulation of PVH neurons in mice elicited escape jumping, a typical defensive behavior. We mapped PVH outputs that densely terminate in the ventral midbrain area, and found that activation of the PVH→ventral midbrain (vMB) circuit produced profound defensive behavioral changes, including escape jumping, hiding, hyperlocomotion, and learned aversion. Electrophysiological recordings showed excitatory post-synaptic input onto ventral midbrain neurons via PVH fiber activation, and in vivo studies demonstrated that glutamate transmission from PVH→vMB was required for the evoked behavioral responses. Photostimulation of PVH→vMB fibers induced cFos expression mainly in non-dopaminergic neurons. Using a dual optogenetic-chemogenetic strategy, we further revealed that escape jumping and hiding were partially contributed by the activation of midbrain glutamatergic neurons. Taken together, our work unveils a hypothalamic-vMB circuit that encodes defensive properties, which may be implicated in normal stress-induced defensive responses.

Significance Statement
Paraventricular hypothalamus (PVH) neurons are known to be involved in various homeostatic regulation. Despite the known activation of PVH neurons by various stresses, whether these neurons are directly involved in defensive behaviors during stressful events is not clear. This study reveals a direction projection from PVH to ventral midbrain (vMB) regions. Acute activation of either PVH neurons or specific PVH→vMB projections elicited stress, escape jumping, hiding and learned aversion, all related to defensive behaviors, which was partially contributed by midbrain glutamatergic neurons. Our study thus identifies a previously unknown role for the PVH→vMB neural pathway in promoting a defensive behavioral program.

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