Abstract
Hes1 regulates the maintenance and proliferation of neural stem/progenitor cells as an essential effector of the Notch signaling pathway. Although Notch signaling is also involved in the functions of mature neurons in learning and memory and in the risk factors for mental disorders such as schizophrenia and bipolar disorder, the in-vivo role of Hes1 in mature neurons remains unknown. Here, we found that Hes1 is expressed by subsets of both excitatory and inhibitory neurons in the adult mouse brain, and that Hes1 expression is induced by neuronal stimulation. Furthermore, inactivation of Hes1 in excitatory neurons resulted in abnormal fear and anxiety behaviors concomitantly with higher neuronal excitability in the amygdala, while inactivation of Hes1 in inhibitory neurons resulted in increased sociability and perseverative tendencies. These results indicated that Hes1 is functionally important for normal behaviors not only in excitatory neurons but also in inhibitory neurons in the adult brain.
Highlights
Notch signaling regulates the maintenance and proliferation of neural stem/progenitor cells and glial versus neuronal differentiation in the developing nervous system[1]
To test the possibility that Hes[1] expression might be induced by neuronal stimulation, we focused on the visual cortex and assessed whether Hes[1] expression can be induced by visual stimulation
We first showed that Hes[1] is expressed by both excitatory and inhibitory mature neurons in the adult mouse brain, and that Hes[1] expression is induced by neuronal stimulation in vivo
Summary
Notch signaling regulates the maintenance and proliferation of neural stem/progenitor cells and glial versus neuronal differentiation in the developing nervous system[1]. NICD is transferred into the nucleus, where it forms a complex with the DNA-binding factor Rbpj and the transcriptional co-activator Mastermind-like[1] This complex activates the expression of various downstream genes such as Hes[1] and Hes[5], which encode basic helix-loop-helix transcriptional repressors[1]. As an essential Notch signaling effector, Hes[1] plays important roles in the maintenance and proliferation of neural stem/progenitor cells and glial versus neuronal differentiation in the developing nervous system[11,12,13]. Hes[1] antagonizes the effects of β-amyloid and increases the survival of cultured hippocampal neurons[15] These results provide evidence that Hes[1] regulates in vitro neuronal activity, but the in vivo functions of Hes[1] in the adult brain still remain to be analyzed. We performed behavior analyses of these cKO mice and found that Hes[1] is functionally important for normal behaviors in excitatory neurons and in inhibitory neurons in the adult brain
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