Carbachol-induced long-term synaptic depression is enhanced during senescence at hippocampal CA3-CA1 synapses.
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.
Kumar
Ashok
A
Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, Florida 32610-0244, USA. Kash@mbi.ufl.edu
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D056654:CA3 Region, Hippocampal / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D002121:Calcium Channel Blockers; D018679:Cholinergic Agonists; D018691:Excitatory Amino Acid Antagonists; D011500:Protein Synthesis Inhibitors; D000841:Anisomycin; D015763:2-Amino-5-phosphonovalerate; D002217:Carbachol; D009543:Nifedipine