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How success feeds success-- mouse study may tell how

From:Admin PubTime:Jul 14, 2017 Visits:609

Getting to the top of social hierarchy is often not a matter of body size or brute strength, but rather determined by intrinsic mental factors such as grit, as well as extrinsic factors such as history of winning. For example, social dominance can be reinforced by a phenomenon known as the “winner effect”, whereby animals increase their probability of victory after previous winnings. However, the neural mechanism that mediates these intrinsic and extrinsic factors was poorly understood. On July 14, 2017, Professor Hailan Hu’s research group from Zhejiang University in China published a research article entitled Winning History Remodels Thalamo-PFC Circuit to Reinforce Social Dominance (Zhou and Zhu et al.) to address this problem in the journal Science.


Six years earlier, Hu’s group reported using the dominance tube test to measure social hierarchy status in mice (Wang et al., Science, 2011). They discovered that by changing the strength of synaptic connections (through which brain cells communicate with each other) in a brain region called the medial prefrontal cortex (mPFC), they can make mice climb up or move down the social ladder. However, the acute requirement of mPFC during ongoing social competition and the upstream neural circuit that regulates mPFC activity in dominance behaviors were essentially unknown. It was also unclear whether the “winner effect” can be generalized, in other words, whether dominance acquired in one type of competition can transfer to another behavioral type.


In the current study, graduate student Tingting Zhou, Hong Zhu and Zhengxiao Fan from Hailan Hu’s lab built on their earlier work and addressed the above questions by applying cutting-edge techniques including in vivo single-unit electrophysiology recording, optogenetics, chemicogenetics and in vivo optic LTP and LTD. Several discoveries were made:


1. They established that activation of dorsal medial prefrontal cortex (dmPFC) is both necessary and sufficient to induce instant (within seconds) winning in dominance contests. Specifically, by optogenetically isolating a synaptic input from mediodorsal thalamus (MDT) to dmPFC, they were able to selectively manipulate synapses driven by this input and establish a causal relationship between the activity of the MDT-dmPFC circuit and mental-effort-based dominance behavior. Importantly, mPFC activation does not seem to boost dominance by enhancing basal aggression level or physical strength, but rather by initiating and maintaining more effortful behaviors during social competition.


2. With in vivo optogenetic LTP and LTD experiments, they provided strong evidence that synapses in the MDT-dmPFC pathway may encode previous winning/losing history, identifying the first neural circuit for mediating the “winner effect” in mammals.


3. They discovered and provided neural circuit mechanism for a generalized form of “winner effect”, where dominance acquired in one behavior can transfer to another type of social contest. Previous studies of the “winner effect” were restricted to the impact of winning on the same behavioral paradigm. Given that animals are dealing with different forms of competitions in setting up the social hierarchy, the generalized “winner effect” that Zhou et al. describe here is of considerable evolutionary significance. For example, it may allow a monkey who succeeds in fighting for bananas earlier to occupy a more comfortable resting spot later. Such reciprocal reinforcement between winning in different behavioral paradigms would help to accelerate the establishment of a stable dominance hierarchy.


Through this work, Hu’s group identifies for the first time the MDT-dmPFC circuit as an important neural substrate mediating both the intrinsic (mental strength) and extrinsic (history of winning) factors for social hierarchy determination.As the lack of social competitive drive prevents individuals from realizing their potential and is a hallmark of many psychiatric disorders, their results will shed important light on treating the motivational defects in these psychiatric diseases.


This work was carried out by graduate students Tingting Zhou, Hong Zhu and Zhengxiao Fan et al., under the supervision of Dr. Hailan Hu. The study was completed at the Zhejiang University Interdisciplinary Institute of Neuroscience and Technology (ZIINT) and Center for Neuroscience, School of Medicine at Zhejiang University, Hangzhou, China.