Coincident glutamatergic and cholinergic inputs transiently depress glutamate release at rat schaffer collateral synapses.
The mammalian hippocampus, together with subcortical and cortical areas, is responsible for some forms of learning and memory. Proper hippocampal function depends on the highly dynamic nature of its circuitry, including the ability of synapses to change their strength for brief to long periods of time. In this study, we focused on a transient depression of glutamatergic synaptic transmission at Schaffer collateral synapses in acute hippocampal slices. The depression of evoked excitatory postsynaptic current (EPSC) amplitudes, herein called transient depression, follows brief trains of synaptic stimulation in stratum radiatum of CA1 and lasts for 2-3 min. Depression results from a decrease in presynaptic glutamate release, as NMDA-receptor-mediated EPSCs and composite EPSCs are depressed similarly and depression is accompanied by an increase in the paired-pulse ratio. Transient depression is prevented by blockade of metabotropic glutamate and acetylcholine receptors, presumably located presynaptically. These two receptor types--acting together--cause depression. Blockade of a single receptor type necessitates significantly stronger conditioning trains for triggering depression. Addition of an acetylcholinesterase inhibitor enables depression from previously insufficient conditioning trains. Furthermore, a strong coincident, but not causal, relationship existed between presynaptic depression and postsynaptic internal Ca(2+) release, emphasizing the potential importance of functional interactions between presynaptic and postsynaptic effects of convergent cholinergic and glutamatergic inputs to CA1. These convergent afferents, one intrinsic to the hippocampus and the other likely originating in the medial septum, may regulate CA1 network activity, the induction of long-term synaptic plasticity, and ultimately hippocampal function.
Gipson
Keith E
KE
Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
Yeckel
Mark F
MF
D000109:Acetylcholine / Q000378:metabolism*; D000344:Afferent Pathways / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018756:GABA Antagonists / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D008954:Models, Biological; D018408:Patch-Clamp Techniques / Q000379:methods; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D018680:Cholinergic Antagonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D005971:Glutamates; D000109:Acetylcholine; D002118:Calcium