Rims1-KO Mouse

Rims1, also known as Rab3-interacting molecule 1, is a key protein involved in neurotransmitter release. It is associated with the neurotransmitter release cycle and the organization of presynaptic active zones. Rims1 forms dynamic and condensed assemblies with RIM-BP through liquid-liquid phase separation, which can enrich voltage-gated Ca2+ channels for efficient synaptic transmissions [1]. It is also involved in the cAMP-EPAC-PKCε-RIM1α signaling cascade that regulates presynaptic long-term potentiation and motor learning [3].

In a study generating dopamine-neuron-specific knockout mice of RIM (a form of gene knockout), action-potential-induced dopamine release was disrupted. These mice showed strongly impaired rapid in vivo dopamine dynamics, yet baseline dopamine persisted and supported spontaneous movement. However, reward-oriented behavior was impaired in these knockout mice, suggesting that Rims1-mediated action-potential-induced dopamine release is dispensable for movement initiation but promotes motivation and performance during reward-guided behaviors [2].

In conclusion, Rims1 is crucial for neurotransmitter release and the regulation of synaptic function. The gene knockout mouse models have revealed its role in differentiating between motor function and reward-oriented behaviors, contributing to our understanding of how the nervous system controls movement and motivation.

References:

1. Wu, Xiandeng, Cai, Qixu, Shen, Zeyu, Du, Shengwang, Zhang, Mingjie. 2019. RIM and RIM-BP Form Presynaptic Active-Zone-like Condensates via Phase Separation. In Molecular cell, 73, 971-984.e5. doi:10.1016/j.molcel.2018.12.007. https://pubmed.ncbi.nlm.nih.gov/30661983/

2. Cai, Xintong, Liu, Changliang, Tsutsui-Kimura, Iku, Uchida, Naoshige, Kaeser, Pascal S. 2024. Dopamine dynamics are dispensable for movement but promote reward responses. In Nature, 635, 406-414. doi:10.1038/s41586-024-08038-z. https://pubmed.ncbi.nlm.nih.gov/39415006/

3. Wang, Xin-Tai, Zhou, Lin, Dong, Bin-Bin, De Zeeuw, Chris I, Shen, Ying. 2023. cAMP-EPAC-PKCε-RIM1α signaling regulates presynaptic long-term potentiation and motor learning. In eLife, 12, . doi:10.7554/eLife.80875. https://pubmed.ncbi.nlm.nih.gov/37159499/