Transcription factor expressed in neurons of the brain that regulates the excitatory-inhibitory balance within neural circuits and is required for contextual memory in the hippocampus (PubMed:18815592, PubMed:22194569, PubMed:23029555, PubMed:24201284, PubMed:24855953). Plays a key role in the structural and functional plasticity of neurons (PubMed:23172225). Acts as an early-response transcription factor in both excitatory and inhibitory neurons, where it induces distinct but overlapping sets of late-response genes in these two types of neurons, allowing the synapses that form on inhibitory and excitatory neurons to be modified by neuronal activity in a manner specific to their function within a circuit, thereby facilitating appropriate circuit responses to sensory experience (PubMed:24201284, PubMed:24855953). In excitatory neurons, activates transcription of BDNF, which in turn controls the number of GABA-releasing synapses that form on excitatory neurons, thereby promoting an increased number of inhibitory synapses on excitatory neurons (PubMed:18815592, PubMed:22194569, PubMed:24201284). In inhibitory neurons, regulates a distinct set of target genes that serve to increase excitatory input onto somatostatin neurons, probably resulting in enhanced feedback inhibition within cortical circuits (PubMed:24855953). The excitatory and inhibitory balance in neurons affects a number of processes, such as short-term and long-term memory, acquisition of experience, fear memory, response to stress and social behavior (PubMed:18815592, PubMed:22194569, PubMed:23029555, PubMed:24201284, PubMed:27238022). Acts as a regulator of dendritic spine development in olfactory bulb granule cells in a sensory-experience-dependent manner by regulating expression of MDM2 (PubMed:25088421). Efficient DNA binding requires dimerization with another bHLH protein, such as ARNT, ARNT2 or BMAL1 (PubMed:14701734, PubMed:15363889, PubMed:19284974). Can activate the CME (CNS midline enhancer) element (PubMed:14701734, PubMed:15363889). Efficient DNA binding requires dimerization with another bHLH protein (PubMed:14701734, PubMed:15363889, PubMed:19284974). Heterodimer; forms a heterodimer with ARNT, ARNT2 or BMAL1 (PubMed:14701734, PubMed:15363889, PubMed:19284974). Mainly expressed in brain (PubMed:14701734, PubMed:15363889). Expressed in the limbic system and olfactory bulb (PubMed:15363889, PubMed:25088421). Specifically expressed in CA1 and CA3 region of the hippocampus after contextual learning (at protein level) (PubMed:22194569, PubMed:23029555). Also expressed in pancreatic beta cells (PubMed:26663079). Induced upon calcium influx (PubMed:26663079). Expression is regulated by neuronal activity (at protein level) (PubMed:18815592, PubMed:22194569, PubMed:24201284, PubMed:24855953). Induced in CA3 region of the hippocampus after contextual learning (PubMed:22194569). Induced following sensory input in newborn olfactory bulb interneurons (PubMed:25088421). Induced in the medial prefrontal cortex cells of the brain following experiences with positive valence (PubMed:27238022). Induced in pancreatic beta cells in response to calcium influx (PubMed:26663079). Down-regulated by REST (PubMed:24291638). Transcripts are regulated by a subset of miRNAs, such as miR-203, miR-224 and miR-744, that bind to its 3'-UTR region and down-regulate its expression (PubMed:24291638, PubMed:27189618). Ubiquitinated, leading to degradation by the proteosome. Mice appear anxious and hyperactive, are prone to seizures and have a shortened lifespan compared with their wild-type littermates (PubMed:18815592, PubMed:19001414, PubMed:23029555, PubMed:25549857). Mice show learning and memory deficits: while having intact memories 5 minutes after training, memory is significantly reduced one hour or 24 hours following training, suggesting that both short-term memory and long-term memory are impaired (PubMed:22194569). Mice show social and cognitive defects: they are hyperactive in a novel environment, spend less time exploring, show higher social dominance than their wild-type littermates and display pre-pulse inhibition, working memory, long-term memory and cognitive flexibility deficits (PubMed:23029555). When exposed to an enriched environment, a significantly less frequent and slightly smaller amplitude inhibitory postsynaptic current is observed (PubMed:24201284). Mice show a reduction in the dendritic spine density in olfactory bulb granule cells, leading to impaired odor discrimination learning (PubMed:25088421). Mice also show increased vulnerability to juvenile stress: mice exposed to chronic mild stress during adolescence, but not during adulthood, develop prefrontal cortex-dependent cognitive deficits in adulthood (PubMed:25911220).