Price Michaela E, McCool Brian A
Neuroscience and Alcohol Research Training Programs, Wake Forest School of Medicine, Winston-Salem, NC, United States.
Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, United States.
Front Cell Neurosci. 2022 Apr 14;16:857550. doi: 10.3389/fncel.2022.857550. eCollection 2022.
Chronic intermittent ethanol and withdrawal (CIE/WD) produces alcohol dependence, facilitates anxiety-like behavior, and increases post-CIE alcohol intake. The basolateral amygdala (BLA) is one of several brain regions that regulates anxiety-like behavior and alcohol intake through downstream projections to the nucleus accumbens (NAC) and bed nucleus of the stria terminalis (BNST), respectively. Previous studies revealed that CIE/WD induces input- and sex-specific adaptations to glutamatergic function in the BLA. The BLA receives information from two distinct input pathways. Glutamatergic afferents from medial structures like the thalamus and prefrontal cortex enter the BLA through the whereas lateral cortical structures like the anterior insula cortex enter the BLA through the external capsule. CIE/WD increases presynaptic glutamatergic function at synapses and postsynaptic function at external capsule synapses. Previous studies sampled neurons throughout the BLA, but did not distinguish between projection-specific populations. The current study investigated BLA neurons that project to the NAC (BLA-NAC neurons) or the BNST (BLA-BNST neurons) as representative "reward" and "aversion" BLA neurons, and showed that CIE/WD alters glutamatergic function and excitability in a projection- and sex-specific manner. CIE/WD increases glutamate release from inputs only onto BLA-BNST neurons. At external capsule synapses, CIE/WD increases postsynaptic glutamatergic function in male BLA-NAC neurons and female BLA-BNST neurons. Subsequent experiments demonstrated that CIE/WD enhanced the excitability of male BLA-NAC neurons and BLA-BNST neurons in both sexes when glutamatergic but not GABAergic function was intact. Thus, CIE/WD-mediated increased glutamatergic function facilitates hyperexcitability in male BLA-NAC neurons and BLA-BNST neurons of both sexes.
慢性间歇性乙醇摄入与戒断（CIE/WD）会导致酒精依赖，引发类似焦虑的行为，并增加CIE后的酒精摄入量。基底外侧杏仁核（BLA）是通过分别向下伏隔核（NAC）和终纹床核（BNST）的下游投射来调节类似焦虑行为和酒精摄入的几个脑区之一。先前的研究表明，CIE/WD会诱导BLA中谷氨酸能功能的输入特异性和性别特异性适应性变化。BLA从两条不同的输入通路接收信息。来自丘脑和前额叶皮质等内侧结构的谷氨酸能传入纤维通过 进入BLA，而来自前岛叶皮质等外侧皮质结构的谷氨酸能传入纤维则通过外囊进入BLA。CIE/WD增加了 突触处的突触前谷氨酸能功能和外囊突触处的突触后功能。先前的研究对整个BLA中的神经元进行了采样，但没有区分投射特异性群体。当前的研究调查了投射到NAC的BLA神经元（BLA-NAC神经元）或投射到BNST的BLA神经元（BLA-BNST神经元），将其作为代表性的“奖赏”和“厌恶”BLA神经元，并表明CIE/WD以投射和性别特异性的方式改变谷氨酸能功能和兴奋性。CIE/WD仅增加了 输入到BLA-BNST神经元上的谷氨酸释放。在外囊突触处，CIE/WD增加了雄性BLA-NAC神经元和雌性BLA-BNST神经元的突触后谷氨酸能功能。随后的实验表明，当谷氨酸能而非GABA能功能完好时，CIE/WD增强了雄性BLA-NAC神经元以及两性的BLA-BNST神经元的兴奋性。因此，CIE/WD介导的谷氨酸能功能增加促进了雄性BLA-NAC神经元以及两性的BLA-BNST神经元的过度兴奋。
