Arico Carolyn, Bagley Elena E, Carrive Pascal, Assareh Neda, McNally Gavan P
School of Psychology, UNSW Sydney, Australia.
Discipline of Pharmacology, University of Sydney, Australia.
Neurobiol Learn Mem. 2017 Oct;144:186-197. doi: 10.1016/j.nlm.2017.07.006. Epub 2017 Jul 14.
The midbrain periaqueductal gray (PAG) has been implicated in the generation and transmission of a prediction error signal that instructs amygdala-based fear and extinction learning. However, the PAG also plays a key role in the expression of conditioned fear responses. The evidence for a role of the PAG in fear learning and extinction learning has been obtained almost exclusively using PAG-dependent fear responses. It is less clear whether the PAG regulates fear learning when other measures of learned fear are used. Here we combined a chemogenetic approach, permitting excitation or inhibition of neurons in the ventrolateral PAG (VLPAG), with conditioned suppression as the measure of learned fear to assess the role of VLPAG in the acquisition and extinction of fear learning. We show that chemogenetic excitation of VLPAG (with some encroachment on lateral PAG [LPAG]) impairs acquisition of fear and, conversely, chemogenetic inhibition impairs extinction of fear. These effects on fear and extinction learning were specific to the combination of DREADD expression and injection of CNO because they were observed relative to both eYFP controls injected with CNO as well as DREADD expressing controls injected with vehicle. Taken together, these results show that activity of L/VLPAG neurons regulates both the acquisition and extinction of Pavlovian fear learning.
中脑导水管周围灰质(PAG)与一种预测误差信号的产生和传递有关,该信号指导基于杏仁核的恐惧和消退学习。然而,PAG在条件性恐惧反应的表达中也起着关键作用。PAG在恐惧学习和消退学习中起作用的证据几乎完全是通过依赖PAG的恐惧反应获得的。当使用其他习得性恐惧的测量方法时,PAG是否调节恐惧学习尚不清楚。在这里,我们将一种化学遗传学方法(允许对腹外侧PAG [VLPAG]中的神经元进行兴奋或抑制)与条件性抑制作为习得性恐惧的测量方法相结合,以评估VLPAG在恐惧学习的获得和消退中的作用。我们表明,VLPAG的化学遗传学兴奋(对外侧PAG [LPAG]有一定程度的影响)会损害恐惧的获得,相反,化学遗传学抑制会损害恐惧的消退。这些对恐惧和消退学习的影响是DREADD表达和CNO注射组合所特有的,因为相对于注射CNO的eYFP对照以及注射载体的DREADD表达对照都观察到了这些影响。综上所述,这些结果表明L/VLPAG神经元的活动调节巴甫洛夫式恐惧学习的获得和消退。