Division of Molecular Neuroscience, Department of Biomedicine, University of Basel, 4055 Basel, Switzerland
University Psychiatric Clinics, University of Basel, 4002 Basel, Switzerland.
J Neurosci. 2024 Mar 6;44(10):e1120232024. doi: 10.1523/JNEUROSCI.1120-23.2024.
Protein kinase C (PKC) functions are essential for synaptic plasticity, learning, and memory. However, the roles of specific members of the PKC family in synaptic function, learning, and memory are poorly understood. Here, we investigated the role of individual PKC homologs for synaptic plasticity in and found a differential role for and , but not and in associative olfactory learning and memory. More specifically we show that PKC-2 is essential for associative learning and TPA-1 for short-term associative memory (STAM). Using endogenous labeling and cell-specific rescues, we show that TPA-1 and PKC-2 are required in AVA for their functions. Previous studies demonstrated that olfactory learning and memory in are tied to proper synaptic content and trafficking of AMPA-type ionotropic glutamate receptor homolog GLR-1 in the AVA command interneurons. Therefore, we quantified synaptic content, transport, and delivery of GLR-1 in AVA and showed that loss of and leads to decreased transport and delivery but only a subtle decrease in GLR-1 levels at synapses. AVA-specific expression of both PKC-2 and TPA-1 rescued these defects. Finally, genetic epistasis showed that PKC-2 and TPA-1 likely act in the same pathway to control GLR-1 transport and delivery, while regulating different aspects of olfactory learning and STAM. Thus, our data tie together cell-specific functions of 2 PKCs to neuronal and behavioral outcomes in , enabling comparative approaches to understand the evolutionarily conserved role of PKC in synaptic plasticity, learning, and memory.
蛋白激酶 C(PKC)的功能对于突触可塑性、学习和记忆至关重要。然而,PKC 家族特定成员在突触功能、学习和记忆中的作用仍知之甚少。在这里,我们研究了个体 PKC 同源物在突触可塑性中的作用,并发现 和 而不是 和 在联想性嗅觉学习和记忆中发挥着不同的作用。更具体地说,我们表明 PKC-2 对于联想学习是必需的,而 TPA-1 对于短期联想记忆(STAM)是必需的。通过内源性标记和细胞特异性拯救实验,我们表明 TPA-1 和 PKC-2 在 AVA 中对于它们的功能是必需的。先前的研究表明,在 中,嗅觉学习和记忆与 AVA 命令中间神经元中 AMPA 型离子型谷氨酸受体同源物 GLR-1 的适当突触内容和运输有关。因此,我们量化了 AVA 中的突触内容、运输和 GLR-1 的传递,并表明 和 的缺失导致运输和传递减少,但突触处 GLR-1 水平仅略有下降。在 AVA 中特异性表达 PKC-2 和 TPA-1 可以挽救这些缺陷。最后,遗传上位性表明 PKC-2 和 TPA-1 可能在同一途径中作用,以控制 GLR-1 的运输和传递,同时调节嗅觉学习和 STAM 的不同方面。因此,我们的数据将 2 个 PKC 的细胞特异性功能与 中的神经元和行为结果联系起来,使我们能够采用比较方法来理解 PKC 在突触可塑性、学习和记忆中的进化保守作用。