Excitation-neurogenesis coupling in adult neural stem/progenitor cells

Neuron. 2004 May 27;42(4):535-52. doi: 10.1016/s0896-6273(04)00266-1.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Basic Helix-Loop-Helix Transcription Factors
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, L-Type / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics*
  • Female
  • Gene Expression Regulation, Developmental / genetics
  • Hippocampus / cytology
  • Hippocampus / growth & development*
  • Hippocampus / metabolism
  • Homeodomain Proteins / genetics
  • Inhibitor of Differentiation Protein 2
  • Microtubule-Associated Proteins / metabolism
  • Nerve Net / cytology
  • Nerve Net / drug effects
  • Nerve Net / metabolism
  • Nerve Tissue Proteins / genetics
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / genetics
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Rats
  • Rats, Inbred F344
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Repressor Proteins*
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / genetics
  • Transcription Factor HES-1
  • Transcription Factors / genetics

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Calcium Channels, L-Type
  • DNA-Binding Proteins
  • Hes1 protein, rat
  • Homeodomain Proteins
  • Id2 protein, rat
  • Inhibitor of Differentiation Protein 2
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Receptors, N-Methyl-D-Aspartate
  • Repressor Proteins
  • Transcription Factor HES-1
  • Transcription Factors
  • NeuroD protein