Abstract：
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.NEW & NOTEWORTHY 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.
摘要：
胆碱能中间神经元（ChIs）提供纹状体中乙酰胆碱的主要来源，并已成为行为灵活性的关键调节剂，动机，和联想学习。在背侧纹状体（DS），ChIs显示异质点火模式。这里,我们研究了ChIs在伏隔核（NAc）壳中的自发放电模式，腹侧纹状体的一个区域。我们确定了四个不同的ChI发射信号：常规的单次穿刺，不规则的单尖峰，有节奏的爆发，以及由爆发活动和常规单尖峰组成的混合模式模式。与男性相比，女性的ChI的放电率较低，并且与男性相比，混合模式放电模式的比例较高，而常规单尖峰神经元的比例较低。我们进一步观察到，在整个发情周期中，与其他阶段相比，发情期的特征是不规则ChI放电模式的比例更高。使用来自男性和女性的汇总数据，我们研究了应激相关神经肽促肾上腺皮质激素释放因子(CRF)如何影响这些放电模式.ChI发射模式显示出对CRF的不同敏感性。这转化为整个发情周期对CRF的差异ChI敏感性。此外，CRF将ChI发射模式的比例转移到更有规律的尖峰活动，而不是爆破模式。最后,我们发现反复的应激源暴露改变了NAc核心的ChI发射模式和对CRF的敏感性，但不是NAc外壳。这些发现突出了ChI发射模式的异质性，这可能对伏隔依赖的动机行为有影响。背侧和腹侧纹状体内的新和注意胆碱能中间神经元（ChIs）可对网络输出和动机行为产生重大影响。然而,腹侧纹状体内ChIs的放电模式和神经调节，特别是伏隔核(NAc)壳，研究不足。这里,我们报告说，NAc壳ChIs具有异质的ChI放电模式，这些模式是不稳定的，并且可以通过与压力相关的神经肽促肾上腺皮质激素释放因子（CRF）和发情周期进行调节。
