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Social avoidance is a common phenomenon in many mental disorders, which is manifested as a lack of interest in social activities, and even the appearance of social activities that trigger strong negative emotions.
Social avoidance can be caused by a variety of reasons, with some suggesting that strong social frustration impairs the function of reward-related brain regions of the brain, so that social activities are no longer rewarding, exacerbating social avoidance behavior
.
In basic research, chronic social frustration stress (CSDS) models have been widely used to analyze the neurobiological mechanism between social trauma susceptibility and stress resistance, and CSDS can significantly reduce the social exploration behavior of mice and increase the social avoidance of mice.
It also reduces the sugar water preference behavior of mice and reduces the natural reward
of mice.
But whether social avoidance in mice was due to increased social phobia or impairment of social reward remains unclear
.
On November 30, 2022, the team of Scott Russo of the Icahn School of Medicine at Mount Sinai, New York, published a research paper titled "Social trauma engages lateral septum circuitry to occlude social reward" in Nature, demonstrating CSDS Social avoidance in the depression model occurs because of impaired social reward function and reveals the neural mechanism
by which social frustration blocks social reward at the circuit level.
1
Disorders of social reward in stress-susceptible mice
To investigate how CSDS affects social interaction and social reward, the researchers performed CSDS modeling on 7-week-old C57 mice, which were divided into stress-susceptible mice (SUS) and stress-resistant mice (RES)based on the proportion of social interaction of the mice.
Subsequently, the invader detection (RI) experiment and the social condition location preference (sCPP) experiment were performed on the mice, and it was found that during the RI detection, RES mice showed positive social interaction towards invader mice, while SUS mice showed significantly reduced social interaction
.
The sCPP test also found that social interaction was also reduced between SUS mice and mice, and there was no significant difference in reduced social interaction with CSDS, indicating that CSDS reduced social reward
in mice.
Figure 1: CSDS reduces social reward in mice
2
Overactivation of NT neurons in the LS brain region of stress-sensitive mice
Causes social reward disorder
In order to study the neural circuit mechanism of social reward disorder in mice with SUS, the researchers used clear brain technology (iDISCO) to perform whole-brain FOS imaging to detect the difference in the expression of neuronal cFos in the brain when faced with invaders in mice after CSDS, and found that Fos-positive neurons in the lateral septate nucleus (LS) of female mice and male mice with SUS increased
significantly.
Subsequently, a large number of neurotensin (NT)-positive neurons of LS were found to be activated
by in situ hybridization experiments.
The use of chemogenetics to inhibit NT-positive neurons in the LS brain region increased the social exploration time of mice and improved social reward behavior
.
Figure 2: Inhibition of NT neurons in LS brain regions improves social reward behavior in mice
3
LS brain regions project to NT neurons of AHN and NAc
Regulate social reward behavior
The neural circuits of NT neurons in the LS brain region that regulate social reward behavior were studied.
Using viral tracing techniques, NAc brain regions, AHN brain regions and PAG brain regions were found to be downstream
of the projection of NT neurons.
Using optogenetics to activate the above three types of projections, it was found that NT neurons activating LS-NAc and LS-AHN could reduce the social reward behavior of mice, but did not affect the social avoidance behavior
of mice.
NT neurons that activate LS-PAG have no effect
on social reward behavior.
summary
In this paper, it is found that social frustration stress activates NT-positive neurons in LS brain regions of male and female mice, thereby enhancing the NT-capable social circuits of LS-NAc and LS-AHN, impairing the social reward of mice, and aggravating the social avoidance
of mice.
This study lays a solid foundation
for understanding the neural circuit mechanisms by which trauma mediates social reward injury.
【References】
Li, L.
, Durand-de Cuttoli, R.
, Aubry, A.
V.
et al.
Social trauma engages lateral septum circuitry to occlude social reward.
Nature (2022).
https://doi.
org/10.
1038/s41586-022-05484-5
The images in the article are from references
