Activity-dependent Regulation of Inhibitory Synaptic Transmission in Hippocampal Neurons

Nat Neurosci. 2006 May;9(5):642-9. doi: 10.1038/nn1677. Epub 2006 Apr 2.

Abstract

Neural activity regulates the number and properties of GABAergic synapses in the brain, but the mechanisms underlying these changes are unclear. We found that blocking spike activity globally in developing hippocampal neurons from rats reduced the density of GABAergic terminals as well as the frequency and amplitude of miniature inhibitory postsynaptic currents (mIPSCs). Chronic inactivity later in development led to a reduction in the mIPSC amplitude, without any change in GABAergic synapse density. By contrast, hyperpolarizing or abolishing spike activity in single neurons did not alter GABAergic synaptic inputs. Suppressing activity in individual presynaptic GABAergic neurons also failed to decrease synaptic output. Our results indicate that GABAergic synapses are regulated by the level of activity in surrounding neurons. Notably, we found that the expression of GABAergic plasticity involves changes in the amount of neurotransmitter in individual vesicles.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Drug Interactions
  • Electric Stimulation / methods
  • Glutamate Decarboxylase / metabolism
  • Hippocampus / cytology*
  • Isoenzymes / metabolism
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Membrane Proteins / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neural Inhibition / radiation effects
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurons / radiation effects
  • Patch-Clamp Techniques / methods
  • Phosphinic Acids / pharmacology
  • Potassium Channels, Inwardly Rectifying / genetics
  • Potassium Channels, Inwardly Rectifying / metabolism
  • Pyridines / pharmacology
  • Rats
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Synaptic Transmission / radiation effects
  • Tetrodotoxin / pharmacology
  • Transfection / methods
  • Vesicular Glutamate Transport Protein 1 / metabolism

Substances

  • (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid
  • Carrier Proteins
  • Isoenzymes
  • Kir2.1 channel
  • MAP2 protein, rat
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Phosphinic Acids
  • Potassium Channels, Inwardly Rectifying
  • Pyridines
  • Slc17a7 protein, rat
  • Vesicular Glutamate Transport Protein 1
  • gephyrin
  • Tetrodotoxin
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2