title: Contribution of Ih to the relative facilitation of synaptic responses induced by carbachol in the entorhinal cortex during repetitive stimulation of the parasubiculum.
abstract: Neurons in the superficial layers of the entorhinal cortex provide the hippocampus with the majority of its cortical sensory input, and also receive the major output projection from the parasubiculum. This puts the parasubiculum in a position to modulate the activity of entorhinal neurons that project to the hippocampus. These brain areas receive cholinergic projections that are active during periods of theta- and gamma-frequency electroencephalographic (EEG) activity. The purpose of this study was to investigate how cholinergic receptor activation affects the strength of repetitive synaptic responses at these frequencies in the parasubiculo-entorhinal pathway and the cellular mechanisms involved. Whole-cell patch-clamp recordings of rat layer II medial entorhinal neurons were conducted using an acute slice preparation, and responses to 5-pulse trains of stimulation at theta- and gamma-frequency delivered to the parasubiculum were recorded. The cholinergic agonist carbachol (CCh) suppressed the amplitude of single synaptic responses, but also produced a relative facilitation of synaptic responses evoked during stimulation trains. The N-methyl-d-aspartate (NMDA) glutamate receptor blocker APV did not significantly reduce the relative facilitation effect. However, the hyperpolarization-activated cationic current (Ih) channel blocker ZD7288 mimicked the relative facilitation induced by CCh, suggesting that CCh-induced inhibition of Ih could produce the effect by increasing dendritic input resistance (Rin). Inward-rectifying and leak K(+) currents are known to interact with Ih to affect synaptic excitability. Application of the K(+) channel antagonist Ba(2+) depolarized neurons and enhanced temporal summation, but did not block further facilitation of train-evoked responses by ZD7288. The Ih-dependent facilitation of synaptic responses can therefore occur during reductions in inward-rectifying potassium current (IKir) associated with dendritic depolarization. Thus, in addition to cholinergic reductions in transmitter release that are known to facilitate train-evoked responses, these findings emphasize the role of inhibition of Ih in the integration of synaptic inputs within the entorhinal cortex during cholinergically-induced oscillatory states, likely due to enhanced summation of excitatory postsynaptic potentials (EPSPs) induced by increases in dendritic Rin.
authors.affiliation: Centre for Studies in Behavioural Neurobiology, Department of Psychology, Concordia University, Montréal, Québec H4B 1R6, Canada.
authors.forename: D W
authors.initials: DW
authors.lastname: Sparks
authors.affiliation: Centre for Studies in Behavioural Neurobiology, Department of Psychology, Concordia University, Montréal, Québec H4B 1R6, Canada. Electronic address: andrew.chapman@concordia.ca.
authors.forename: C A
authors.initials: CA
authors.lastname: Chapman
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004558:Electric Stimulation; D018728:Entorhinal Cortex / Q000187:drug effects / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018679:Cholinergic Agonists; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels; D011743:Pyrimidines; D016194:Receptors, N-Methyl-D-Aspartate; C082246:ICI D2788; C056639:2-amino-5-phosphopentanoic acid; D002217:Carbachol; D014633:Valine; D000109:Acetylcholine
keywords: I(h); IK(ir); NMDA; acetylcholine; entorhinal cortex; parasubiculum