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https://www.readbyqxmd.com/read/28449268/ventral-but-not-dorsal-hippocampus-inactivation-impairs-reward-memory-expression-and-retrieval-in-contexts-defined-by-proximal-cues
#1
Sadia Riaz, Anett Schumacher, Seyon Sivagurunathan, Matthijs Van Der Meer, Rutsuko Ito
The hippocampus (HPC) has been widely implicated in the contextual control of appetitive and aversive conditioning. However, whole hippocampal lesions do not invariably impair all forms of contextual processing, as in the case of complex biconditional context discrimination, leading to contention over the exact nature of the contribution of the HPC in contextual processing. Moreover, the increasingly well-established functional dissociation between the dorsal (dHPC) and ventral (vHPC) subregions of the HPC has been largely overlooked in the existing literature on hippocampal-based contextual memory processing in appetitively-motivated tasks...
April 27, 2017: Hippocampus
https://www.readbyqxmd.com/read/28446950/analgesic-effect-of-17%C3%AE-estradiol-on-nucleus-paragigantocellularis-lateralis-of-male-rats-mediated-via-gabaa-receptors
#2
Roghaieh Khakpay, Maryam Azaddar, Fatemeh Khakpay, Homeira Hatami Nemati
INTRODUCTION: Beside its autonomic functions, the nucleus paragigantocellularis lateralis (LPGi) is involved in the descending pain modulation. 17β-Estradiol is a neuroactive steroid found in several brain areas such as LPGi. Intra-LPGi microinjection of 17β-estradiol can elicit the analgesic responses. 17β-Estradiol modulates nociception by binding to estrogenic receptors as well as allosteric interaction with other membrane-bound receptors like GABAA receptors. This study aimed to examine the role of GABAA receptors in the pain modulating effect of intra-LPGi injection of 17β-estradiol...
January 2017: Basic and Clinical Neuroscience
https://www.readbyqxmd.com/read/28446587/temporal-integration-and-1-f-power-scaling-in-a-circuit-model-of-cerebellar-interneurons
#3
Reinoud Maex, Boris Samuel Gutkin
Inhibitory interneurons interconnected via electrical and chemical (GABAA receptor) synapses form extensive circuits in several brain regions. They are thought to be involved in timing and synchronization through fast feed-forward control of principal neurons. Theoretical studies have shown, however, that whereas self-inhibition does indeed reduce response duration, lateral inhibition, in contrast, may generate slow response components through a process of gradual disinhibition. Here we simulated a circuit of interneurons (stellate and basket cells) of the molecular layer of the cerebellar cortex, and observed circuit time-constants that could rise, depending on the parameter values, to more than one second...
April 26, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28445782/the-immunohistochemical-distribution-of-the-gabaa-receptor-%C3%AE-1-%C3%AE-2-%C3%AE-3-%C3%AE-2-3-and-%C3%AE-2-subunits-in-the-human-thalamus
#4
H J Waldvogel, M Munkle, W van Roon-Mom, H Mohler, R L M Faull
The GABAA receptor is the most abundant inhibitory receptor in the human brain and is assembled from a variety of different subunit subtypes which determines their pharmacology and physiology. To determine which GABAA receptor subunit proteins are found in the human thalamus we investigated the distribution of five major GABAA receptor subunits α1, α2, α3, β2,3 and γ2 using immunohistochemical techniques. The α1-, β2,3- and γ2- subunits which combine to form a benzodiazepine sensitive GABAA receptor showed the most intense levels of staining and were the most common subunits found throughout the human thalamus especially in the ventral and posterior nuclear groups...
April 23, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28445721/nacho-mediates-nicotinic-acetylcholine-receptor-function-throughout-the-brain
#5
Jose A Matta, Shenyan Gu, Weston B Davini, Brian Lord, Edward R Siuda, Anthony W Harrington, David S Bredt
Neuronal nicotinic acetylcholine receptors (nAChRs) participate in diverse aspects of brain function and mediate behavioral and addictive properties of nicotine. Neuronal nAChRs derive from combinations of α and β subunits, whose assembly is tightly regulated. NACHO was recently identified as a chaperone for α7-type nAChRs. Here, we find NACHO mediates assembly of all major classes of presynaptic and postsynaptic nAChR tested. NACHO acts at early intracellular stages of nAChR subunit assembly and then synergizes with RIC-3 for receptor surface expression...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28444767/the-dual-orexin-receptor-antagonist-dora-22-lowers-histamine-levels-in-the-lateral-hypothalamus-and-prefrontal-cortex-without-lowering-hippocampal-acetylcholine
#6
Lihang Leon Yao, Andres Ramirez, Anthony J Roecker, Steven Fox, Jason Uslaner, Sean M Smith, Robert Hodgson, Paul J Coleman, John J Renger, Christopher J Winrow, Anthony L Gotter
Chronic insomnia is defined as a persistent difficulty with sleep initiation maintenance or non-restorative sleep. The therapeutic standard of care for this condition is treatment with gamma-aminobutyric acid (GABA)A receptor modulators, which promote sleep but are associated with a panoply of side effects, including cognitive and memory impairment. Dual orexin receptor antagonists (DORAs) have recently emerged as an alternative therapeutic approach that acts via a distinct and more selective wake-attenuating mechanism with the potential to be associated with milder side effects...
April 26, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28444246/lateral-orbitofrontal-cortical-modulation-on-medial-prefrontal-cortex-amygdala-pathway-differential-regulation-of-intra-amygdala-gabaa-and-gabab-receptors
#7
Chun-Hui Chang
Background: The basolateral complex of the amygdala receives inputs from neocortical areas, including the medial prefrontal cortex (mPFC) and lateral orbitofrontal cortex (lOFC). Earlier studies have shown that lOFC activation exerts an inhibitory gating on mPFC-amygdala information flow. Here we examined the individual role of GABAA and GABAB receptors in this process. Methods: In vivo extracellular single-unit recordings were done in anesthetized rats. We searched amygdala neurons that fire in response to mPFC activation, tested lOFC gating at different delays (lOFC-mPFC delays: 25, 50, 100, 250, 500, and 1000 ms), and examined differential contribution of GABAA and GABAB receptors with iontophoresis...
April 22, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28442369/further-evaluation-of-the-potential-anxiolytic-activity-of-imidazo-1-5-a-1-4-diazepin-agents-selective-for-%C3%AE-2-3-containing-gabaa-receptors
#8
J M Witkin, R Cerne, M Wakulchik, J S, S D Gleason, T M Jones, G Li, L A Arnold, Jun-Xu Li, J M Schkeryantz, K R Methuku, J M Cook, M M Poe
Positive allosteric modulators of GABAA receptors transduce a host of beneficial effects including anxiolytic actions. We have recently shown that bioavailability and anxiolytic-like activity can be improved by eliminating the ester functionality in imidazo[1,5-a][1,4]diazepines. In the present series of experiments, we further substantiate the value of heterocyle replacement of the ester for potential treatment of anxiety. None of the three esters was active in a Vogel conflict test in rats that detects anxiolytic drugs like diazepam...
April 22, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28442196/mechanism-of-neuronal-activity-and-synaptic-transmission-in-rostral-ventrolateral-medulla
#9
Liangchen Zhao, Tianji Liu, Rutao Xu, Liu He, Man Duan, Dejun Xu
Rostral ventrolateral medulla (RVLM) plays an essential role in blood pressure homeostasis. This study was aimed to investigate the mechanism of neuronal activity and synaptic transmission in the RVLM. Medulla oblongata slices were carefully obtained from brainstem of rats. With continues perfusion of artificial cerebrospinal fluid (ACSF), the spontaneous firing of slices and amplitudes were assayed by conventional whole cell patch-clamp recording after addition of gamma-aminobutyric acid (GABA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and N-methyl d-aspartate (NMDA)...
April 22, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28440659/alleviation-of-multiple-asthmatic-pathologic-features-with-orally-available-and-subtype-selective-gabaa-receptor-modulators
#10
Gloria S Forkuo, Amanda N Nieman, Nina Y Yuan, Revathi Kodali, Olivia B Yu, Nicolas M Zahn, Rajwana Jahan, Guanguan Li, Michael Rajesh Stephen, Margaret L Guthrie, Michael M Poe, Benjamin D Hartzler, Ted William Harris, Gene T Yocum, Charles W Emala, Douglas A Steeber, Douglas C Stafford, James M Cook, Leggy A Arnold
We describe pharmacokinetic and pharmacodynamic properties of two novel oral drug candidates for asthma. Phenolic α4β3γ2 GABAAR selective compound 1 and acidic α5β3γ2 selective GABAAR positive allosteric modulator compound 2 relaxed airway smooth muscle ex vivo and attenuated airway hyperresponsiveness (AHR) in a murine model of asthma. Importantly, compound 2 relaxed acetylcholine contracted human tracheal airway smooth muscle strips. Oral treatment of compound 1 and 2 decreased eosinophils in bronchoalveolar lavage fluid in ovalbumin sensitized and challenged mice, thus exhibiting anti-inflammatory properties...
April 25, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28438981/acute-inflammation-reveals-gabaa-receptor-mediated-nociception-in-mouse-dorsal-root-ganglion-neurons-via-pge2-receptor-4-signaling
#11
In Jeong Jang, Alexander J Davies, Nozomi Akimoto, Seung Keun Back, Pa Reum Lee, Heung Sik Na, Hidemasa Furue, Sung Jun Jung, Yong Ho Kim, Seog Bae Oh
Gamma-aminobutyric acid (GABA) depolarizes dorsal root ganglia (DRG) primary afferent neurons through activation of Cl(-) permeable GABAA receptors but the physiologic role of GABAA receptors in the peripheral terminals of DRG neurons remains unclear. In this study, we investigated the role of peripheral GABAA receptors in nociception using a mouse model of acute inflammation. In vivo, peripheral administration of the selective GABAA receptor agonist muscimol evoked spontaneous licking behavior, as well as spinal wide dynamic range (WDR) neuron firing, after pre-conditioning with formalin but had no effect in saline-treated mice...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28434791/neuronal-cells-derived-from-human-induced-pluripotent-stem-cells-as-a-functional-tool-of-melanocortin-system
#12
Nobuko Yamada-Goto, Yukari Ochi, Goro Katsuura, Yui Yamashita, Ken Ebihara, Michio Noguchi, Junji Fujikura, Daisuke Taura, Masakatsu Sone, Kiminori Hosoda, Paul E Gottschall, Kazuwa Nakao
BACKGROUND: The preparation of human neurons derived from human induced pluripotent stem (iPS) cells can serve as a potential tool for evaluating the physiological and pathophysiological properties of human neurons and for drug development. METHODS: In the present study, the functional activity in neuronal cells differentiated from human iPS cells was observed. RESULTS: The differentiated cells expressed mRNAs for classical neuronal markers (microtubule-associated protein 2, β-tubulin III, calbindin 1, synaptophysin and postsynaptic density protein 95) and for subunits of various excitatory and inhibitory transmitters (NR1, NR2A, NR2B, GABAA α1)...
April 7, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28433421/strain-specific-programming-of-prenatal-ethanol-exposure-across-generations
#13
Daniel O Popoola, Michael E Nizhnikov, Nicole M Cameron
Behavioral consequences of prenatal alcohol exposure (PAE) can be transmitted from in utero-exposed F1 generation to their F2 offspring. This type of transmission is modulated by genetic and epigenetic mechanisms. This study investigated the intergenerational consequences of prenatal exposure to a low ethanol dose (1 g/kg) during gestational days 17-20, on ethanol-induced hypnosis in adolescent male F1 and F2 generations, in two strains of rats. Adolescent Long-Evans and Sprague-Dawley male rats were tested for sensitivity to ethanol-induced hypnosis at a 3...
January 4, 2017: Alcohol
https://www.readbyqxmd.com/read/28432493/effect-of-pharmacological-modulation-of-activity-of-metabotropic-glutamate-receptors-on-their-gene-expression-after-excitotoxic-damage-in-hippocampal-neurons
#14
E V Pershina, M V Kapralova, V I Arkhipov
Microinjection of kainic acid into rat hippocampus causes excitotoxic neuronal damage predominantly in the CA3 and CA1 fields. These lesions can be significantly reduced by simultaneous administration of MPEP, a negative allosteric modulator of type 5 metabotropic glutamate receptors, and LY354740, an agonist of type 2 metabotropic glutamate receptors. The decrease in neuronal death in the hippocampus during pharmacological modulation was paralleled by adaptive changes in gene expression. In the hippocampus, gene expression of type 5 postsynaptic metabotropic glutamate receptor was close to the control level, and in the frontal cortex expression of the gene of α1-subunit of the GABAA receptor returned to normal...
April 22, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28431741/chloride-dysregulation-seizures-and-cerebral-edema-a-relationship-with-therapeutic-potential
#15
REVIEW
Joseph Glykys, Volodymyr Dzhala, Kiyoshi Egawa, Kristopher T Kahle, Eric Delpire, Kevin Staley
Pharmacoresistant seizures and cytotoxic cerebral edema are serious complications of ischemic and traumatic brain injury. Intraneuronal Cl(-) concentration ([Cl(-)]i) regulation impacts on both cell volume homeostasis and Cl(-)-permeable GABAA receptor-dependent membrane excitability. Understanding the pleiotropic molecular determinants of neuronal [Cl(-)]i - cytoplasmic impermeant anions, polyanionic extracellular matrix (ECM) glycoproteins, and plasmalemmal Cl(-) transporters - could help the identification of novel anticonvulsive and neuroprotective targets...
April 18, 2017: Trends in Neurosciences
https://www.readbyqxmd.com/read/28429004/binding-site-opening-by-loop-c-shift-and-chloride-ion-pore-interaction-in-the-gabaa-receptor-model
#16
M A Michałowski, S Kraszewski, J W Mozrzymas
GABAA receptors (GABAARs) are crucial in mediating inhibition in the adult mammalian brain. Although the kinetics of this receptor has been extensively studied, the molecular picture of interactions occurring at various channel conformations remains elusive. While electrophysiology combined with mutagenesis sheds light on the role of specific residues, ultrastructural studies reveal static structures which, in the case of GABAARs, are limited to the β3 homomer. To take advantage of the newest crystal structures of cys-loop receptors, a homology model of α1β2γ2 GABAAR in the unbound closed state was built using a template of the homomeric glycine receptor in the closed state...
April 21, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28428226/rapid-throughput-analysis-of-gabaa-receptor-subtype-modulators-and-blockers-using-disbac1-3-membrane-potential-red-dye
#17
Atefeh Mousavi Nik, Brandon Pressly, Vikrant Singh, Shane Antrobus, Susan Hulsizer, Michael A Rogawski, Heike Wulff, Isaac N Pessah
Fluorometric Imaging Plate Reader (FLIPR®) membrane potential dye (FMP-Red-Dye) is a proprietary tool for basic discovery and high throughput drug screening for G-protein coupled receptors and ion channels. We optimized and validated this potentiometric probe to assay functional modulators of heterologous expressed GABAA receptor (GABAAR) isoforms (synaptic α1β3γ2, extrasynaptic α4β3δ, and β3 homopentomers). High-resolution mass spectrometry identified FMP-Red-dye as DisSBAC1(3). GABAAR expressing cells equilibrated with FMP-Red-Dye exhibited depolarized equilibrium membrane (Em) potentials compared to GABAAR-null cells...
April 20, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28426550/neuropathic-pain-after-chronic-nerve-constriction-may-not-correlate-with-chloride-dysregulation-in-mouse-trigeminal-nucleus-caudalis-neurons
#18
Alberto Castro, Ying Li, Charles Raver, Ramesh Chandra, Radi Masri, Mary Kay Lobo, Asaf Keller
Changes in chloride reversal potential in rat spinal cord neurons have previously been associated with persistent pain in nerve injury and inflammation models. These changes correlate with a decrease in the expression of the potassium% chloride transporter, KCC2, and with increases in neuronal excitability. Here, we test the hypothesis that similar changes occur in mice with neuropathic pain induced by chronic constriction injury of the trigeminal infraorbital nerve (CCI¬-ION). This model allows us to distinguish an acute pain phase (3-¬5 days after injury) from a persistent pain phase (12¬-14 days after CCI-¬ION)...
April 18, 2017: Pain
https://www.readbyqxmd.com/read/28426226/brain-uptake-of-bioactive-flavones-in-scutellariae-radix-and-its-relationship-to-anxiolytic-effect-in-mice
#19
Sophia Yui Kau Fong, Chenrui Li, Yiu Cheong Ho, Rui Li, Qian Wang, Yin Cheong Wong, Hong Xue, Zhong Zuo
Scutellariae Radix (SR) and its bioactive flavones elicit a variety of effects in the brain. However, the brain uptake of individual SR flavones and its relationship to the elicited effects after SR administration remain unknown. Moreover, previous studies seldom measured pharmacokinetic and pharmacodynamic outcomes simultaneously. In the current study, the brain uptake of six major SR flavones and the anxiolytic behavior following oral administration of a SR extract at two clinically relevant doses (600 and 1200 mg/kg twice daily) were simultaneously investigated in mice (n=18 per group)...
April 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28424564/new-developments-in-the-management-of-narcolepsy
#20
REVIEW
Vivien C Abad, Christian Guilleminault
Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%-0.18% of the US and Western European populations. Genetic predisposition is suspected because of narcolepsy's strong association with HLA DQB1*06-02, and genome-wide association studies have identified polymorphisms in T-cell receptor loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin-producing neurons; an autoimmune etiology possibly triggered by some environmental agent may precipitate hypocretin neuronal loss...
2017: Nature and Science of Sleep
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