Nicotinic regulation of CREB activation in hippocampal neurons by glutamatergic and nonglutamatergic pathways

Mol Cell Neurosci. 2002 Dec;21(4):616-25. doi: 10.1006/mcne.2002.1202.

Abstract

Activity-dependent gene expression is essential for form and function in the nervous system. Best understood is the role of glutamatergic signaling in controlling such events, but nicotinic signaling can also regulate transcription. We show here that nicotine can alter gene expression in rat hippocampal neurons, as reflected by activation of the transcription factor CREB and appearance of the immediate early gene product c-Fos. The process depends on both CaM and MAP kinases and on calcium release from internal stores. Part of the nicotinic effect is mediated via glutamatergic transmission, even in the absence of action potentials. Voltage-gated calcium channels are not necessary for nicotine-induced activation of CREB in hippocampal neurons. The low levels of sustained nicotinic stimulation required for transcriptional effects are consistent with those likely to be achievable either by the normal septal cholinergic innervation of the hippocampus or by repeated tobacco usage.

Publication types

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

MeSH terms

  • Acetylcholine / metabolism
  • Acetylcholine / pharmacology
  • Animals
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Cyclic AMP Response Element-Binding Protein / drug effects
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / physiology
  • Glutamic Acid / metabolism*
  • Hippocampus / drug effects
  • Hippocampus / growth & development*
  • Hippocampus / metabolism
  • Neural Pathways / drug effects
  • Neural Pathways / growth & development*
  • Neural Pathways / metabolism
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nicotine / pharmacology*
  • Proto-Oncogene Proteins c-fos / drug effects
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Nicotinic / drug effects
  • Receptors, Nicotinic / metabolism
  • Synapses / drug effects
  • Synapses / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • alpha7 Nicotinic Acetylcholine Receptor

Substances

  • Calcium Channels
  • Chrna7 protein, rat
  • Cyclic AMP Response Element-Binding Protein
  • Proto-Oncogene Proteins c-fos
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • Glutamic Acid
  • Nicotine
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Acetylcholine