Carbachol-induced long-term synaptic depression is enhanced during senescence at hippocampal CA3-CA1 synapses

J Neurophysiol. 2010 Aug;104(2):607-16. doi: 10.1152/jn.00278.2010. Epub 2010 May 26.


Dysregulation of the cholinergic transmitter system is a hallmark of Alzheimer's disease and contributes to an age-associated decline in memory performance. The current study examined the influence of carbachol, a cholinergic receptor agonist, on synaptic transmission over the course of aging. Extracellular excitatory postsynaptic field potentials were recorded from CA3-CA1 synapses in acute hippocampal slices obtained from young adult (5-8 mo) and aged (22-24 mo) male Fischer 344 rats. Bath application of carbachol elicited a transient depression of synaptic transmission, which was followed by a long-lasting depression (CCh-LTD) observed 90 min after carbachol cessation in both age groups. However, the magnitude of CCh-LTD was significantly larger in senescent animals and was attenuated by N-methyl-D-aspartate receptor blockade in aged animals. Blockade of L-type Ca(2+) channels inhibited CCh-LTD to a greater extent in aged animals compared to young adults. Finally, the expression of CCh-LTD was dependent on protein synthesis. The results indicate that altered Ca(2+) homeostasis or muscarinic activation of Ca(2+) signaling contribute to the enhanced CCh-LTD during senescence.

Publication types

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

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Age Factors
  • Analysis of Variance
  • Animals
  • Anisomycin / pharmacology
  • CA1 Region, Hippocampal / physiology*
  • CA3 Region, Hippocampal / physiology*
  • Calcium Channel Blockers / pharmacology
  • Carbachol / pharmacology*
  • Cholinergic Agonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Electric Stimulation / methods
  • Excitatory Amino Acid Antagonists / pharmacology
  • In Vitro Techniques
  • Long-Term Synaptic Depression / drug effects*
  • Male
  • Nifedipine / pharmacology
  • Patch-Clamp Techniques / methods
  • Protein Synthesis Inhibitors / pharmacology
  • Rats
  • Rats, Inbred F344
  • Synapses / drug effects
  • Synapses / physiology*


  • Calcium Channel Blockers
  • Cholinergic Agonists
  • Excitatory Amino Acid Antagonists
  • Protein Synthesis Inhibitors
  • Anisomycin
  • 2-Amino-5-phosphonovalerate
  • Carbachol
  • Nifedipine