Romo-Parra H, Blaesse P, Sosulina L, Pape H-C
Institute of Physiology I, Westfälische Wilhelms-Universität Münster, Münster, Germany
Institute of Physiology I, Westfälische Wilhelms-Universität Münster, Münster, Germany.
J Neurophysiol. 2015 May 1;113(9):3421-31. doi: 10.1152/jn.00045.2015. Epub 2015 Mar 18.
Neurosteroids are formed de novo in the brain and can modulate both inhibitory and excitatory neurotransmission. Recent evidence suggests that the anxiolytic effects of neurosteroids are mediated by the amygdala, a key structure for emotional and cognitive behaviors. Tonic inhibitory signaling via extrasynaptic type A γ-aminobutyric acid receptors (GABA(A)Rs) is known to be crucially involved in regulating network activity in various brain regions including subdivisions of the amygdala. Here we provide evidence for the existence of tonic GABAergic inhibition generated by the activation of δ-subunit-containing GABA(A)Rs in neurons of the lateral section of the mouse central amygdala (CeAl). Furthermore, we show that neurosteroids play an important role in the modulation of tonic GABAergic inhibition in the CeAl. Taken together, these findings provide new mechanistic insights into the effects of pharmacologically relevant neurosteroids in the amygdala and might be extrapolated to the regulation of anxiety.
神经甾体在大脑中从头合成,可调节抑制性和兴奋性神经传递。最近的证据表明,神经甾体的抗焦虑作用是由杏仁核介导的,杏仁核是情绪和认知行为的关键结构。已知通过突触外A型γ-氨基丁酸受体(GABA(A)Rs)的紧张性抑制信号在调节包括杏仁核各亚区在内的各种脑区的网络活动中起关键作用。在这里,我们提供证据表明,在小鼠中央杏仁核外侧部(CeAl)的神经元中,含δ亚基的GABA(A)Rs激活可产生紧张性GABA能抑制。此外,我们表明神经甾体在CeAl紧张性GABA能抑制的调节中起重要作用。综上所述,这些发现为药理学相关神经甾体在杏仁核中的作用提供了新的机制见解,并可能外推至焦虑的调节。