Falkner Annegret L, Grosenick Logan, Davidson Thomas J, Deisseroth Karl, Lin Dayu
Institute of Neuroscience, New York University School of Medicine, New York, New York, USA.
Department of Bioengineering, Neuroscience Program, Stanford University, Stanford, California, USA.
Nat Neurosci. 2016 Apr;19(4):596-604. doi: 10.1038/nn.4264. Epub 2016 Mar 7.
In many vertebrate species, certain individuals will seek out opportunities for aggression, even in the absence of threat-provoking cues. Although several brain areas have been implicated in the generation of attack in response to social threat, little is known about the neural mechanisms that promote self-initiated or 'voluntary' aggression-seeking when no threat is present. To explore this directly, we utilized an aggression-seeking task in which male mice self-initiated aggression trials to gain brief and repeated access to a weaker male that they could attack. In males that exhibited rapid task learning, we found that the ventrolateral part of the ventromedial hypothalamus (VMHvl), an area with a known role in attack, was essential for aggression-seeking. Using both single-unit electrophysiology and population optical recording, we found that VMHvl neurons became active during aggression-seeking and that their activity tracked changes in task learning and extinction. Inactivation of the VMHvl reduced aggression-seeking behavior, whereas optogenetic stimulation of the VMHvl accelerated moment-to-moment aggression-seeking and intensified future attack. These data demonstrate that the VMHvl can mediate both acute attack and flexible seeking actions that precede attack.
在许多脊椎动物物种中,某些个体即便在没有引发威胁的线索时,也会主动寻找攻击机会。尽管已有多个脑区被认为与应对社会威胁时的攻击行为产生有关,但对于在没有威胁的情况下促进自我发起或“自愿”寻求攻击行为的神经机制,我们却知之甚少。为了直接探究这一问题,我们采用了一项寻求攻击行为的任务,在此任务中,雄性小鼠会自我发起攻击试验,以便能短暂且反复地接近一只较弱的雄性小鼠并对其进行攻击。在表现出快速任务学习能力的雄性小鼠中,我们发现腹内侧下丘脑的腹外侧部分(VMHvl),这一在攻击行为中具有已知作用的脑区,对于寻求攻击行为至关重要。通过单单元电生理学和群体光学记录,我们发现VMHvl神经元在寻求攻击行为期间变得活跃,并且它们的活动跟踪了任务学习和消退过程中的变化。VMHvl失活会减少寻求攻击行为,而对VMHvl进行光遗传学刺激则会加速即时的寻求攻击行为,并增强未来的攻击行为。这些数据表明,VMHvl既能介导急性攻击行为,也能介导攻击行为之前灵活的寻求行为。