The activity-dependent transcription factor NPAS4 regulates domain-specific inhibition

摘要

单个神经元能够区分在它们的细胞体和树突上rn接收的突触输入，但行为会怎样影响它们的平衡却一直不清楚。现在Michael Greenberg及同事发现，小鼠海马神经元通过转录因子NPAS4及其目标基因产物"脑源性神经营养因子"（BDNF)的水平的增加来对感觉输入信号的增多做出反应，而BDNF随后则促进细胞体上的抑制性突触，同时使那些在树突上的抑制性突触失去稳定性。因此，单个神经元是通过重新描绘它们抑制性输入的分布图、限制它们的细胞体输出、同时促进它们树突上的可塑性来对感官刺激做出反应的。%A heterogeneous population of inhibitory neurons controls the flow of information through a neural circuit. Inhibitory synapses that form on pyramidal neuron dendrites modulate the summation of excitatory synaptic potentials and prevent the generation of dendritic calcium spikes. Precisely timed somatic inhibition limits both the number of action potentials and the time window during which firing can occur. The activity-dependent transcription factor NPAS4 regulates inhibitory synapse number and function in cell culture, but how this transcription factor affects the inhibitory inputs that form on distinct domains of a neuron in vivo was unclear. Here we show that in the mouse hippocampus behaviourally driven expression of NPAS4 coordinates the redistribution of inhibitory synapses made onto a CA1 pyramidal neuron, simultaneously increasing inhibitory synapse number on the cell body while decreasing the number of inhibitory synapses on the apical dendrites. This rearrangement of inhibition is mediated in part by the NP AS4 target gene brain derived neurotrophic factor (Bdnf), which specifically regulates somatic, and not dendritic, inhibition. These findings indicate that sensory stimuli, by inducing NPAS4 and its target genes, differentially control spatial features of neuronal inhibition in a way that restricts the output of the neuron while creating a dendritic environment that is permissive for plasticity.