Abstract
Zona incerta (ZI), a largely inhibitory subthalamic region connected with many brain areas, has been suggested to serve as an integrative node for modulation of behaviors and physiological states, such as fear memory conditioning and aversion responses. It is, however, unclear whether ZI regulated the repeated social defeat stress (RSDS)-induced social conditioned place aversion (CPA) and post-traumatic stress disorder (PTSD)-like behaviors. In this study, the function of ZI was silenced via bilateral injection of tetanus toxin light chain (Tet-tox), a neurotoxin that completely blocks the evoked synaptic transmissions, expressing adeno-associated viruses (AAVs). We found ZI silencing: (1) significantly blocked the expression of RSDS-induced social CPA with no effect on the innate preference; (2) significantly enhanced the anxiety level in mice experienced RSDS with no effect on the locomotion activity; (3) altered the PTSD-associated behaviors, including the promotion of spatial cognitive impairment and the preventions of PPI deficit and social avoidance behavior. These effects were not observed on non-stressed mice. In summary, our results suggest the important role of ZI in modulating RSDS-induced social CPA and PTSD-like behaviors.
Highlights
The zona incerta (ZI) is a subthalamic region with extensive connections throughout the brain
Mice were randomly divided into 4 groups and were injected with associated viruses (AAVs)- green fluorescent protein (GFP) or AAV-tetanus toxin light chain (Tet-tox), respectively, according to the grouping described in materials and methods section
Previous study has shown that inactivation of the medial ZI strongly impaired fear conditioning via blocking the initial acquisition of fear memory and the remote retrieval of previously acquired fear memory; silencing of ZI parvalbumin-positive (PV+) neurons but not the tyrosine hydroxylase-positive (TH+) neurons and somatostatinpositive (SST+) neurons showed similar results (Zhou et al, 2018), indicating that ZI was involved in the modulation of fear conditioning memory, and the ZI PV+ neurons are uniquely essential for the acquisition of fear conditioning memory and the remote retrieval
Summary
The zona incerta (ZI) is a subthalamic region with extensive connections throughout the brain. It plays diverse roles in processing sensory information, regulating behaviors, conveying motivational states, and participating in neural plasticity (Zhang and van den Pol, 2017; Zhou et al, 2018; Zhao et al, 2019; Hormigo et al, 2020). Activation of the GABAergic neurons in the rostral part of ZI suppresses both noisy sound-induced flight and conditioned freezing response via their projections to the periaqueductal gray (Chou et al, 2018), while inactivation of the parvalbumin-positive neurons in the ventral part of the medial ZI or silencing all ZI neurons largely impairs fear conditioning memory acquisition and remote retrieval (Zhou et al, 2018). ZI was, important in modulating responses to aversive stimuli
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