Timing and location of nicotinic activity enhances or depresses hippocampal synaptic plasticity

Neuron. 2001 Jul 19;31(1):131-41. doi: 10.1016/s0896-6273(01)00332-4.

Abstract

This study reveals mechanisms in the mouse hippocampus that may underlie nicotinic influences on attention, memory, and cognition. Induction of synaptic plasticity, arising via generally accepted mechanisms, is modulated by nicotinic acetylcholine receptors. Properly timed nicotinic activity at pyramidal neurons boosted the induction of long-term potentiation via presynaptic and postsynaptic pathways. On the other hand, nicotinic activity on interneurons inhibited nearby pyramidal neurons and thereby prevented or diminished the induction of synaptic potentiation. The synaptic modulation was dependent on the location and timing of the nicotinic activity. Loss of these synaptic mechanisms may contribute to the cognitive deficits experienced during Alzheimer's diseases, which is associated with a loss of cholinergic projections and with a decrease in the number of nicotinic receptors.

Publication types

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

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Acetylcholine / pharmacology*
  • Alzheimer Disease / physiopathology
  • Amino Acid Substitution
  • Animals
  • Bicuculline / pharmacology
  • Heterozygote
  • Hippocampus / physiology*
  • Humans
  • In Vitro Techniques
  • Interneurons / drug effects
  • Interneurons / physiology*
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Mecamylamine / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Models, Animal
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Nicotinic Antagonists / pharmacology
  • Patch-Clamp Techniques
  • Point Mutation
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology*
  • Receptors, Nicotinic / drug effects
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / physiology*
  • Synapses / drug effects
  • Synapses / physiology*
  • alpha7 Nicotinic Acetylcholine Receptor

Substances

  • Chrna7 protein, human
  • Chrna7 protein, mouse
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • Mecamylamine
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • 2-Amino-5-phosphonovalerate
  • Acetylcholine
  • Bicuculline