Orexin-induced Modulation of State-dependent Intrinsic Properties in Thalamic Paraventricular Nucleus Neurons Attenuates Action Potential Patterning and Frequency.
From: Neurosciences, Ottawa Health Research Institute and University of Ottawa, 725 Parkdale Avenue, Ottawa, Ontario, Canada K1Y 4E9.
Neuroscience
- Publish Date: Jul 2007
- ISSN: 0306-4522
- Volume: 147
- Issue: 4
- Pages: 1066-75
- Medium: Print
- Language: English
- Citation (JAMA): Kolaj M, Doroshenko P, Yan Cao X, et al. Orexin-induced Modulation of State-dependent Intrinsic Properties in Thalamic Paraventricular Nucleus Neurons Attenuates Action Potential Patterning and Frequency.. Neuroscience Jul 2007;147:1066-75
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.
Mesh Headings (Keywords): Action Potentials, Animals, Animals, Newborn, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, Electric Stimulation, Excitatory Postsynaptic Potentials, Intracellular Signaling Peptides and Proteins, Midline Thalamic Nuclei, Neurons, Neuropeptides, Patch-Clamp Techniques, Rats, Rats, Wistar
Check for Full Text / PubMed Unique Identifier (PMID): 17600629
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