Synaptic Plasticity In Hippocampal Inhibitory Neurons Tunes Memory Consolidation

Changing the strength of connections between neurons is widely assumed to be the mechanism by which memory traces are encoded and stored in the central nervous system.These changes can be driven by experience-induced neuronal activity and determined by neuronal plasticity.Synaptic plasticity,exemplified by long-term potentiation(LTP),is a fundamental process thought to underlie the long-term storage of information in neural circuits.It has been shown in the past that once the synaptic plasticity is impaired,the ability of learning and memory decreases accordingly.Therefore,uncovering the cellular and molecular mechanisms of LTP has been a fundamental goal in the field of neuroscience,with great significance for guiding the treatment of brain diseases of impaired cognitive functions such as Alzheimer’s disease and intellectual disability.Most studies on LTP have focused on the excitatory synapses onto excitatory neurons,and it has been confirmed that the induction of LTP depends on the activation of a Ca MKII.Inhibitory interneurons also receive excitatory synaptic input,but it remains unclear whether and how LTP is regulated by experience and the relationship between this process and memory.Here,we report that g Ca MKII highly expressed in inhibitory interneurons is the basis for LTP of excitatory synapses onto inhibitory interneurons.The loss of g Ca MKII in parvalbumin-positive(PV+)interneurons selectively inhibited the formation of LTP in interneurons and resulted in impaired long-term memory consolidation in mice.Impaired long-term memory was rescued by re-expression of g Ca MKII in adult hippocampal PV+ interneurons.In summary,we found that g Ca MKII is the long-sought mediator of long-term potentiation for excitatory synapses onto inhibitory interneurons,and plays a gatekeeping role in memory consolidation.This suggests that memory may also be stored in the excitatory synapses onto inhibitory interneurons in a plasticityrelated format.