Experience-induced NPAS4 reduces dendritic inhibition from CCK+ inhibitory neurons and enhances plasticity

Flexibility of neurological systems stems from a host of biological responses to changing experience. When a mouse explores an enriched environment, neurons throughout the brain express the inducible transcription factor NPAS4. In CA1 of the hippocampus, pyramidal neurons that express NPAS4 receive more perisomatic inhibition from cholecystokinin (CCK+) inhibitory neurons and less dendritic inhibition from a previously unidentified inhibitory neuron population. Here, we show that this reduction in dendritic inhibition is specific to synapses made by CCK+ inhibitory neurons and that these NPAS4-dependent changes result in facilitation of theta-burst synaptic plasticity. Thus, NPAS4 expression reorganizes inhibition from a genetically defined population of inhibitory neurons, changing learning rules in response to an animal's interactions with its environment.<b>NEW & NOTEWORTHY</b> How does an inducible transcription factor affect neuronal and circuit function? Here we show that housing mice in an enriched environment induces NPAS4 expression in CA1 pyramidal neurons, leading to a reduction in dendritic inhibition specifically from cholecystokinin (CCK+) inhibitory neurons. This facilitates excitatory synaptic plasticity, indicating a potential mechanistic link between environmental enrichment and enhanced cognitive flexibility.