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      Intrinsic properties and neuropharmacology of midline paraventricular thalamic nucleus neurons

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          Abstract

          Neurons in the midline and intralaminar thalamic nuclei are components of an interconnected brainstem, limbic and prefrontal cortex neural network that is engaged during arousal, vigilance, motivated and addictive behaviors, and stress. To better understand the cellular mechanisms underlying these functions, here we review some of the recently characterized electrophysiological and neuropharmacological properties of neurons in the paraventricular thalamic nucleus (PVT), derived from whole cell patch clamp recordings in acute rat brain slice preparations. PVT neurons display firing patterns and ionic conductances (I T and I H) that exhibit significant diurnal change. Their resting membrane potential (RMP) is maintained by various ionic conductances that include inward rectifier (Kir), hyperpolarization-activated nonselective cation (HCN) and TWIK-related acid sensitive (TASK) K + channels. Firing patterns are regulated by high voltage-activated (HVA) and low voltage-activated (LVA) Ca 2+ conductances. Moreover, transient receptor potential (TRP)-like nonselective cation channels together with Ca 2+- and Na +-activated K + conductances (K Ca; K Na) contribute to unique slow afterhyperpolarizing potentials (sAHPs) that are generally not detectable in lateral thalamic or reticular thalamic nucleus neurons. The excitability of PVT neurons is also modulated by activation of neurotransmitter receptors associated with afferent pathways to PVT and other thalamic midline nuclei. We report on receptor-mediated actions of GABA, glutamate, monoamines and several neuropeptides: arginine vasopressin, gastrin-releasing peptide, thyrotropin releasing hormone and the orexins (hypocretins). This review represents an initial survey of intrinsic and transmitter-sensitive ionic conductances that are deemed to be unique to this population of midline thalamic neurons, information that is fundamental to an appreciation of the role these thalamic neurons may play in normal central nervous system (CNS) physiology and in CNS disorders that involve the dorsomedial thalamus.

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          Most cited references158

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          Metabotropic glutamate receptors: physiology, pharmacology, and disease.

          The metabotropic glutamate receptors (mGluRs) are family C G-protein-coupled receptors that participate in the modulation of synaptic transmission and neuronal excitability throughout the central nervous system. The mGluRs bind glutamate within a large extracellular domain and transmit signals through the receptor protein to intracellular signaling partners. A great deal of progress has been made in determining the mechanisms by which mGluRs are activated, proteins with which they interact, and orthosteric and allosteric ligands that can modulate receptor activity. The widespread expression of mGluRs makes these receptors particularly attractive drug targets, and recent studies continue to validate the therapeutic utility of mGluR ligands in neurological and psychiatric disorders such as Alzheimer's disease, Parkinson's disease, anxiety, depression, and schizophrenia.
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            Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.

            The hypothalamus plays a central role in the integrated control of feeding and energy homeostasis. We have identified two novel neuropeptides, both derived from the same precursor by proteolytic processing, that bind and activate two closely related (previously) orphan G protein-coupled receptors. These peptides, termed orexin-A and -B, have no significant structural similarities to known families of regulatory peptides. prepro-orexin mRNA and immunoreactive orexin-A are localized in neurons within and around the lateral and posterior hypothalamus in the adult rat brain. When administered centrally to rats, these peptides stimulate food consumption. prepro-orexin mRNA level is up-regulated upon fasting, suggesting a physiological role for the peptides as mediators in the central feedback mechanism that regulates feeding behavior.
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              We describe a hypothalamus-specific mRNA that encodes preprohypocretin, the putative precursor of a pair of peptides that share substantial amino acid identities with the gut hormone secretin. The hypocretin (Hcrt) protein products are restricted to neuronal cell bodies of the dorsal and lateral hypothalamic areas. The fibers of these neurons are widespread throughout the posterior hypothalamus and project to multiple targets in other areas, including brainstem and thalamus. Hcrt immunoreactivity is associated with large granular vesicles at synapses. One of the Hcrt peptides was excitatory when applied to cultured, synaptically coupled hypothalamic neurons, but not hippocampal neurons. These observations suggest that the hypocretins function within the CNS as neurotransmitters.
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                Author and article information

                Contributors
                Journal
                Front Behav Neurosci
                Front Behav Neurosci
                Front. Behav. Neurosci.
                Frontiers in Behavioral Neuroscience
                Frontiers Media S.A.
                1662-5153
                17 April 2014
                2014
                : 8
                : 132
                Affiliations
                [1]Neuroscience Program and Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa Ottawa, ON, Canada
                Author notes

                Edited by: Christopher V. Dayas, University of Newcastle, Australia

                Reviewed by: Matthew Philip Parsons, University of British Columbia, Canada; Jaclyn I. Wamsteeker Cusulin, University of Calgary, Canada

                *Correspondence: Leo P. Renaud, Neuroscience Program and Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, 725 Parkdale Ave., Ottawa, ON K1Y 4E9, Canada e-mail: lprenaud@ 123456ohri.ca

                This article was submitted to the journal Frontiers in Behavioral Neuroscience.

                Article
                10.3389/fnbeh.2014.00132
                4029024
                24860449
                91434dfb-32b0-49ae-aa20-c5c32d99cede
                Copyright © 2014 Kolaj, Zhang, Hermes and Renaud.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 26 January 2014
                : 01 April 2014
                Page count
                Figures: 3, Tables: 2, Equations: 1, References: 81, Pages: 178, Words: 13530
                Categories
                Neuroscience
                Review Article

                Neurosciences
                midline thalamic nuclei,electrophysiology,peptides,diurnal and seasonal changes,burst firing

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