Differential modulation by carbachol of four separate excitatory afferent systems to the rat subiculum in vitro.
The subiculum is a limbic cortical region that receives inputs from hippocampus and other parahippocampal regions. We used horizontal brain slices to study the modulatory effects of muscarinic receptor activation on excitatory afferent systems of the subiculum. Multiple inputs are preserved in these slices. Carbachol (CCh, applied to the bath) induced a decrease in the field responses (40-50% at 50 microM; 60% at 100 microM) to CA1, presubicular (PreS), and medial entorhinal (MEC) stimulation. Subicular responses to lateral entorhinal (LEC) stimuli were not depressed. The M1 receptor antagonist pirenzepine at 1 microM was sufficient to reverse most of the CCh-induced depression of afferent excitation, but 10 microM concentrations were required to eliminate the CCh-induced firing in the isolated subiculum. A partial reversal of the CCh-induced depression of afferent excitation was achieved by the M2 receptor antagonist methoctramine (1 or 10 microM), but these concentrations did not prevent CCh-induced firing. When CA1 afferents were repetitively activated with submaximal stimuli in the presence of CCh, population excitatory postsynaptic potentials (EPSPs) showed modest summation, but every response was smaller than a corresponding events in normal media. Population spikes, particularly late spikes in a train, showed pronounced facilitation during CCh exposure. The NMDA receptor antagonist CPP (10 microM) prevented facilitation of responses to repetitive stimulation in the presence of carbachol. We conclude that CA1, PreS, and MEC afferents to the subiculum exhibit CCh sensitivity similar to that established for area CA3 afferents to CA1, and LEC afferents to subiculum exhibit CCh resistance. Our data suggest that much of the hippocampal formation circuitry is modulated by CCh and the properties of this modulation can explain some specific firing characteristics of hippocampal formation neurons in "cholinergic" versus "noncholinergic" brain states.
Kunitake
Ayumi
A
Department of Physiology and Pharmacology, State University of New York, Downstate Medical Center, Brooklyn, New York 11203, USA.
Kunitake
Takato
T
Stewart
Mark
M
D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018728:Entorhinal Cortex / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018679:Cholinergic Agonists; D018691:Excitatory Amino Acid Antagonists; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D016194:Receptors, N-Methyl-D-Aspartate; D002217:Carbachol; D000109:Acetylcholine