Abstract
A wide variety of in vivo manipulations influence neurogenesis in the adult hippocampus. It is not known, however, if adult neural stem/progenitor cells (NPCs) can intrinsically sense excitatory neural activity and thereby implement a direct coupling between excitation and neurogenesis. Moreover, the theoretical significance of activity-dependent neurogenesis in hippocampal-type memory processing networks has not been explored. Here we demonstrate that excitatory stimuli act directly on adult hippocampal NPCs to favor neuron production. The excitation is sensed via Ca(v)1.2/1.3 (L-type) Ca(2+) channels and NMDA receptors on the proliferating precursors. Excitation through this pathway acts to inhibit expression of the glial fate genes Hes1 and Id2 and increase expression of NeuroD, a positive regulator of neuronal differentiation. These activity-sensing properties of the adult NPCs, when applied as an "excitation-neurogenesis coupling rule" within a Hebbian neural network, predict significant advantages for both the temporary storage and the clearance of memories.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Newborn
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Basic Helix-Loop-Helix Transcription Factors
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Calcium Channels, L-Type / drug effects
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Calcium Channels, L-Type / metabolism
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Cell Differentiation / drug effects
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Cell Differentiation / genetics*
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Cells, Cultured
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DNA-Binding Proteins / genetics
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / genetics*
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Female
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Gene Expression Regulation, Developmental / genetics
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Hippocampus / cytology
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Hippocampus / growth & development*
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Hippocampus / metabolism
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Homeodomain Proteins / genetics
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Inhibitor of Differentiation Protein 2
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Microtubule-Associated Proteins / metabolism
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Nerve Net / cytology
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Nerve Net / drug effects
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Nerve Net / metabolism
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Nerve Tissue Proteins / genetics
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / genetics
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism*
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Rats
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Rats, Inbred F344
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Rats, Sprague-Dawley
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Receptors, N-Methyl-D-Aspartate / drug effects
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Receptors, N-Methyl-D-Aspartate / metabolism
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Repressor Proteins*
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Stem Cells / cytology
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Stem Cells / drug effects
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Stem Cells / metabolism*
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Synaptic Transmission / drug effects
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Synaptic Transmission / genetics
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Transcription Factor HES-1
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Transcription Factors / genetics
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Calcium Channels, L-Type
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DNA-Binding Proteins
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Hes1 protein, rat
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Homeodomain Proteins
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Id2 protein, rat
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Inhibitor of Differentiation Protein 2
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Microtubule-Associated Proteins
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Nerve Tissue Proteins
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Receptors, N-Methyl-D-Aspartate
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Repressor Proteins
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Transcription Factor HES-1
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Transcription Factors
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Neurogenic differentiation factor 1