In addition, mice overexpressing Notch1 antisense m RNA (NAS mice) showed impaired early-phase long-term potentiation (LTP) and enhanced long-term depression (LTD) at the CA3-CA1 synapses in the hippocampus .In these genetic models, however, Notch signaling could have been previously altered during development as well as during functional maturation of postmitotic neurons.
Mib1 regulates the endocytosis of Notch ligands to promote Notch activation in the signal-receiving cells [ ablation in the developing brain resulted in complete blockage of Notch signaling and the premature differentiation of radial glial cells, suggesting that Mib1 is essential for Notch signaling during embryonic neurogenesis [ c KO) mice displayed the marked reduction of Notch signaling in the adult brain, but did not exhibit changes in neuronal morphology or structural synaptic connectivity.
However, hippocampus-dependent long-term memories, such as object recognition memory, contextual fear memory, and spatial memory in Morris water maze task, were severely impaired in c KO mice was totally recovered by expression of a constitutively active form of Notch1 (NICD).
These results suggest that Mib1-mediated Notch signaling between excitatory neurons is essential for long-lasting synaptic plasticity and memory formation in the hippocampus. X-gal reactivity was strong in the hippocampus and in the piriform cortex.
Hip, hippocampus; Cor, cortex; Pir, piriform cortex; Tha, thalamus. (B) X-gal reactivity was high in the granule layers of the dentate gyrus (DG) and in the pyramidal layers of the CA1 and CA3 regions. (C) Neu N (left panel) and GFAP staining (right panel) on an X-gal-stained section of the adult brain.
Notch signaling is well recognized as a key regulator of the neuronal fate during embryonic development, but its function in the adult brain is still largely unknown.
Mind bomb-1 (Mib1) is an essential positive regulator in the Notch pathway, acting non-autonomously in the signal-sending cells.
Therefore, genetic ablation of Mib1 in mature neuron would give valuable insight to understand the cell-to-cell interaction between neurons via Notch signaling for their proper function.
Here we show that the inactivation of Mib1 in mature neurons in forebrain results in impaired hippocampal dependent spatial memory and contextual fear memory.
Consistently, hippocampal slices from Mib1-deficient mice show impaired late-phase, but not early-phase, long-term potentiation and long-term depression without change in basal synaptic transmission at SC-CA1 synapses.
The Notch signaling pathway is a signaling module that is evolutionarily conserved from nematodes to human, which plays essential roles in pattern formation and cell fate determination through local cell-cell interactions .
These interactions induce proteolytic cleavages of the Notch receptors, and generate a soluble intracellular domain (Nicd) that translocates to the nucleus to form a transcriptional activator complex with Su(H)/CBF1/RBP-Jκ.