Department of Neuroscience, University of Minnesota-Twin Cities, Minneapolis, Minnesota, United States.
Medical Discovery Team on Addiction, University of Minnesota, Minneapolis, Minnesota, United States.
J Neurophysiol. 2024 Aug 1;132(2):403-417. doi: 10.1152/jn.00348.2023. Epub 2024 Jun 19.
Cholinergic interneurons (ChIs) provide the main source of acetylcholine in the striatum and have emerged as a critical modulator of behavioral flexibility, motivation, and associative learning. In the dorsal striatum (DS), ChIs display heterogeneous firing patterns. Here, we investigated the spontaneous firing patterns of ChIs in the nucleus accumbens (NAc) shell, a region of the ventral striatum. We identified four distinct ChI firing signatures: regular single-spiking, irregular single-spiking, rhythmic bursting, and a mixed-mode pattern composed of bursting activity and regular single spiking. ChIs from females had lower firing rates compared with males and had both a higher proportion of mixed-mode firing patterns and a lower proportion of regular single-spiking neurons compared with males. We further observed that across the estrous cycle, the diestrus phase was characterized by higher proportions of irregular ChI firing patterns compared with other phases. Using pooled data from males and females, we examined how the stress-associated neuropeptide corticotropin releasing factor (CRF) impacts these firing patterns. ChI firing patterns showed differential sensitivity to CRF. This translated into differential ChI sensitivity to CRF across the estrous cycle. Furthermore, CRF shifted the proportion of ChI firing patterns toward more regular spiking activity over bursting patterns. Finally, we found that repeated stressor exposure altered ChI firing patterns and sensitivity to CRF in the NAc core, but not the NAc shell. These findings highlight the heterogeneous nature of ChI firing patterns, which may have implications for accumbal-dependent motivated behaviors. Cholinergic interneurons (ChIs) within the dorsal and ventral striatum can exert a major influence on network output and motivated behaviors. However, the firing patterns and neuromodulation of ChIs within the ventral striatum, specifically the nucleus accumbens (NAc) shell, are understudied. Here, we report that NAc shell ChIs have heterogeneous ChI firing patterns that are labile and can be modulated by the stress-linked neuropeptide corticotropin releasing factor (CRF) and by the estrous cycle.
胆碱能中间神经元 (ChIs) 为纹状体提供了乙酰胆碱的主要来源，并且已成为行为灵活性、动机和联想学习的关键调节剂。在背侧纹状体 (DS) 中，ChIs 表现出异质的放电模式。在这里，我们研究了腹侧纹状体中伏隔核 (NAc) 壳内 ChIs 的自发放电模式。我们确定了四种不同的 ChI 放电特征：规则单峰放电、不规则单峰放电、节律性爆发和由爆发活动和规则单峰放电组成的混合模式。与雄性相比，雌性 ChIs 的放电率较低，并且与雄性相比，混合模式放电的比例更高，规则单峰放电神经元的比例更低。我们进一步观察到，在整个发情周期中，发情期的不规则 ChI 放电模式比例高于其他阶段。使用来自雄性和雌性的合并数据，我们研究了应激相关神经肽促肾上腺皮质释放因子 (CRF) 如何影响这些放电模式。ChI 放电模式对 CRF 表现出不同的敏感性。这导致 CRF 在整个发情周期内对 ChI 的敏感性不同。此外，CRF 将 ChI 放电模式的比例从爆发模式转移到更规则的尖峰活动。最后，我们发现，重复应激暴露改变了 NAc 核心中的 ChI 放电模式和对 CRF 的敏感性，但 NAc 壳中的 ChI 没有改变。这些发现强调了 ChI 放电模式的异质性，这可能对伏隔核依赖的动机行为有影响。背侧和腹侧纹状体中的胆碱能中间神经元 (ChIs) 可以对网络输出和动机行为产生重大影响。然而，腹侧纹状体，特别是伏隔核 (NAc) 壳内的 ChI 的放电模式和神经调制仍未得到充分研究。在这里，我们报告 NAc 壳内的 ChIs 具有异质的 ChI 放电模式，这些模式不稳定，并且可以通过应激相关神经肽促肾上腺皮质释放因子 (CRF) 和发情周期进行调节。
