title: Orexin-induced modulation of state-dependent intrinsic properties in thalamic paraventricular nucleus neurons attenuates action potential patterning and frequency.
abstract: The thalamic paraventricular nucleus (PVT) receives a dense innervation from orexin-synthesizing lateral hypothalamic neurons. Since PVT neurons display state-dependent tonic or low threshold spike-driven burst firing patterns, we examined how the response to exogenously applied orexins might modulate these features. Data were obtained with whole-cell patch clamp recording techniques in rat brain slices prepared during the subjective lights-on period. PVT neurons displayed a mean resting membrane potential of -61+/-6 mV and input conductance of 1.3+/-0.1 nS (n=60). The majority (90/107) of cells tested responded to orexin A and/or orexin B peptides (100-1000 nM), each inducing similar slowly rising and prolonged membrane depolarizations. We next evaluated associated changes in firing patterns and action potential frequency. Of 17 spontaneously silent neurons, 5 were induced into tonic firing and 4 into burst firing modes. Of nine spontaneously bursting neurons, three displayed an increase in burst frequency and in the number of action potentials within a burst. By contrast, another six cells were induced into tonic firing mode, with a marked decrease in instantaneous firing frequency and a shift in their excitatory postsynaptic potential-evoked responses from burst firing patterns to single action potentials. Under voltage clamp, orexins induced inward current (-21.8+/-2.4 pA at -60 mV) in 20/22 cells. In 13 cells, current-voltage (I-V) plots revealed a decrease in net conductance and reversal at -110+/-9 mV, while 3 cells displayed an increase in net conductance that reversed at -26+/-8 mV. These observations imply suppression of potassium and/or induction of nonselective cationic conductances in orexin-induced depolarization in PVT neurons, permitting these peptides to modulate intrinsic state-dependent properties. In vivo, such changes in firing patterns and frequency of action potential discharges could influence neurotransmission through PVT and activity-dependent synaptic plasticity at target sites of these neurons.
authors.affiliation: Neurosciences, Ottawa Health Research Institute and University of Ottawa, 725 Parkdale Avenue, Ottawa, Ontario, Canada K1Y 4E9.
authors.forename: M
authors.initials: M
authors.lastname: Kolaj
authors.forename: P
authors.initials: P
authors.lastname: Doroshenko
authors.forename: X
authors.initials: X
authors.lastname: Yan Cao
authors.forename: E
authors.initials: E
authors.lastname: Coderre
authors.forename: L P
authors.initials: LP
authors.lastname: Renaud
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D020644:Midline Thalamic Nuclei / Q000166:cytology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000494:pharmacology*; D000068797:Orexins; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins