Object location learning in mice requires hippocampal somatostatin interneuron activity and is facilitated by mTORC1-mediated long-term potentiation of their excitatory synapses

[摘要] Hippocampus-dependent learning and memory originate from long-term synaptic changes in hippocampal networks. The activity of CA1 somatostatin interneurons (SOM-INs) during aversive stimulation is necessary for contextual fear memory formation. In addition, mTORC1-dependent long-term potentiation (LTP) of SOM-IN excitatory input synapses from local pyramidal cells (PC-SOM synapses) contributes to the consolidation of fear motivated spatial and contextual memories. Although, it remains unknown if SOM-IN activity and LTP are necessary and sufficient for novelty motivated spatial episodic memory such as the object location memory, and if so when it is required. Here we use optogenetics to examine whether dorsal CA1 SOM-IN activity and LTP are sufficient to regulate object location memory. First, we found that silencing SOM-INs during object location learning impaired memory. Second, optogenetic induction of PC-SOM synapse LTP (TBSopto) given 30 min before object location training, resulted in facilitation of memory. However, in mice with mTORC1 pathway genetically inactivated in SOM-INs, which blocks PC-SOM synapse LTP, TBSopto failed to facilitate object location memory. Our results indicate that SOM-IN activity is necessary during object location learning and that optogenetic induction of PC-SOM synapse LTP is sufficient to facilitate consolidation of object location memory. Thus, hippocampal somatostatin interneuron activity is required for object location learning, a hippocampus-dependent form of novelty motivated spatial learning that is facilitated by plasticity at PC-SOM synapses.

[发布日期] 2022-12-14

[关键词] Dorsal CA1 hippocampus;Somatostatin interneurons;Long-term potentiation;Object location memory;mTORC1;Optogenetic silencing;Optogenetic synaptic plasticity