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https://www.readbyqxmd.com/read/28729628/a-new-approach-for-ratiometric-in-vivo-calcium-imaging-of-microglia
#1
Bianca Brawek, Yajie Liang, Daria Savitska, Kaizhen Li, Natalie Fomin-Thunemann, Yury Kovalchuk, Elizabeta Zirdum, Johan Jakobsson, Olga Garaschuk
Microglia, resident immune cells of the brain, react to the presence of pathogens/danger signals with a large repertoire of functional responses including morphological changes, proliferation, chemotaxis, production/release of cytokines, and phagocytosis. In vitro studies suggest that many of these effector functions are Ca(2+)-dependent, but our knowledge about in vivo Ca(2+) signalling in microglia is rudimentary. This is mostly due to technical reasons, as microglia largely resisted all attempts of in vivo labelling with Ca(2+) indicators...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729445/preferential-disruption-of-prefrontal-gabaergic-function-by-nanomolar-concentrations-of-the-%C3%AE-7nach-negative-modulator-kynurenic-acid
#2
Eden Flores-Barrera, Daniel R Thomases, Daryn K Cass, Ajay Bhandari, Robert Schwarcz, John P Bruno, Kuei Y Tseng
Increased concentrations of kynurenic acid (KYNA) in the prefrontal cortex (PFC) are thought to contribute to the development of cognitive deficits observed in schizophrenia. Although this view is consistent with pre-clinical studies showing a negative impact of prefrontal KYNA elevation on executive function, the mechanism underlying such a disruption remains unclear. Here we measured changes in local field potential responses to ventral hippocampal stimulation in vivo, and conducted whole-cell patch-clamp recordings in brain slices to reveal how nanomolar concentrations of KYNA alter synaptic transmission in the PFC of male adult rats...
July 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28725010/glucose-deficiency-elevates-acid-sensing-ion-channel-2a-expression-and-increases-seizure-susceptibility-in-temporal-lobe-epilepsy
#3
Haitao Zhang, Guodong Gao, Yu Zhang, Yang Sun, Huanfa Li, Shan Dong, Wei Ma, Bei Liu, Weiwen Wang, Hao Wu, Hua Zhang
Brain hypometabolism is a common epilepsy-related finding in both patients and animal models. Fluorodeoxyglucose positron emission tomography studies have shown that recurrent seizures lead to reduced glucose metabolism in certain brain regions, but no studies have definitively determined whether this induces epileptogenesis. There is evidence that acid-sensing ion channel 2a (ASIC2a) affects epilepsy susceptibility. Transcription factor CP2 (TFCP2) regulates ASIC2a expression. We report that suppressed TFCP2 expression and elevated ASIC2a expression were associated with glucose hypometabolism in the hippocampi of humans with epilepsy and of rat epilepsy model brains...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714121/acetylcholine-dependent-upregulation-of-task-1-channels-in-thalamic-interneurons-by-a-smooth-muscle-like-signalling-pathway
#4
Michael Leist, Susanne Rinné, Maia Datunashvili, Ania Aissaoui, Hans-Christian Pape, Niels Decher, Sven G Meuth, Thomas Budde
The dorsal part of the lateral geniculate nucleus (dLGN) is the main thalamic site for state-dependent transmission of visual information. Non-retinal inputs from the ascending arousal system and inhibition provided by γ-aminobutyric acid (GABA)ergic local circuit interneurons (INs) control neuronal activity within the dLGN. In particular, acetylcholine (ACh) depolarizes thalamocortical relay (TC) neurons by inhibiting two-pore domain potassium (K2P ) channels. Conversely, ACh also hyperpolarizes INs via an as-yet-unknown mechanism...
July 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28698388/delayed-cryptochrome-degradation-asymmetrically-alters-the-daily-rhythm-in-suprachiasmatic-clock-neuron-excitability
#5
Sven Wegner, Mino D C Belle, Alun T L Hughes, Casey O Diekman, Hugh D Piggins
Suprachiasmatic nuclei (SCN) neurons contain an intracellular molecular circadian clock and the Cryptochromes (CRY1/2), key transcriptional repressors of this molecular apparatus, are subject to post-translational modification through ubiquitination and targeting for proteosomal degradation by the ubiquitin E3 ligase complex. Loss-of-function point mutations in a component of this ligase complex, Fbxl3, delay CRY1/2 degradation, reduce circadian rhythm strength, and lengthen the circadian period by ∼2.5h...
July 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28696429/glud1-linked-to-schizophrenia-controls-the-burst-firing-of-dopamine-neurons
#6
N Benamer, F Marti, R Lujan, R Hepp, T G Aubier, A A M Dupin, G Frébourg, S Pons, U Maskos, P Faure, Y A Hay, B Lambolez, L Tricoire
Human mutations of the GRID1 gene encoding the orphan delta1 glutamate receptor-channel (GluD1) are associated with schizophrenia but the explicit role of GluD1 in brain circuits is unknown. Based on the known function of its paralog GluD2 in cerebellum, we searched for a role of GluD1 in slow glutamatergic transmission mediated by metabotropic receptor mGlu1 in midbrain dopamine neurons, whose dysfunction is a hallmark of schizophrenia. We found that an mGlu1 agonist elicits a slow depolarizing current in HEK cells co-expressing mGlu1 and GluD1, but not in cells expressing mGlu1 or GluD1 alone...
July 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28682946/cerebral-alterations-following-experimental-multiple-trauma-and-hemorrhagic-shock
#7
Nina Vogt, Christiane Herden, Elke Roeb, Martin Roderfeld, Daphne Eschbach, Thorsten Steinfeldt, Hinnerk Wulf, Steffen Ruchholtz, Eberhard Uhl, Karsten Schöller
Multiple trauma (MT) associated with hemorrhagic shock (HS) might lead to cerebral hypoperfusion and brain damage. We investigated cerebral alterations using a new porcine MT/HS model without traumatic brain injury (TBI) and assessed the neuroprotective properties of mild therapeutic hypothermia. Male pigs underwent standardized MT with HS (45% or 50% loss of blood volume) and resuscitation after 90/120 minutes (T90/T120). In additional groups (TH90/TH120) mild hypothermia (33°C) was induced following resuscitation...
July 4, 2017: Shock
https://www.readbyqxmd.com/read/28667175/the-relevance-of-agrp-neuron-derived-gaba-inputs-to-pomc-neurons-differs-for-spontaneous-and-evoked-release
#8
Andrew R Rau, Shane T Hentges
Hypothalamic agouti-related peptide (AgRP) neurons potently stimulate food intake, whereas proopiomelanocortin (POMC) neurons inhibit feeding. Whether AgRP neurons exert their orexigenic actions, at least in part, by inhibiting anorexigenic POMC neurons remains unclear. Here, the connectivity between GABA-releasing AgRP neurons and POMC neurons was examined in brain slices from male and female mice. Spontaneous GABA-mediated inhibitory postsynaptic currents (sIPSCs) in POMC neurons were unaffected by disturbing GABA release from AgRP neurons either by cell-type-specific deletion of the vesicular GABA transporter or by expression of botulinum toxin in AgRP neurons to prevent VAMP2-dependent vesicle fusion...
June 30, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28666957/functional-perturbation-of-forebrain-principal-neurons-reveals-differential-effects-in-novel-and-well-learned-tasks
#9
Emily T Stoneham, Daniel G McHail, Katelyn N Boggs, Sarah H Albani, Jason A Carty, Rebekah C Evans, Kelly A Hamilton, Victoria M Saadat, Samanza Hussain, Maggie E Greer, Theodore C Dumas
Neural circuits in mammalian brains consist of large numbers of different cell types having different functional properties. To better understand the separate roles of individual neuron types in specific aspects of spatial learning and memory, we perturbed the function of principal neurons in vivo during maze performance or in hippocampal slices during recording of evoked excitatory synaptic potentials. Transgenic mice expressing the Drosophila allatostatin receptor (AlstR) in cortical and hippocampal pyramidal cells were tested on an elevated plus maze, in a Y-maze, and in the Morris water maze...
June 27, 2017: Brain Research
https://www.readbyqxmd.com/read/28656372/increased-gyrification-and-aberrant-adult-neurogenesis-of-the-dentate-gyrus-in-adult-rats
#10
Alejandra Magagna-Poveda, Jillian N Moretto, Helen E Scharfman
A remarkable example of maladaptive plasticity is the development of epilepsy after a brain insult or injury to a normal animal or human. A structure that is considered central to the development of this type of epilepsy is the dentate gyrus (DG), because it is normally a relatively inhibited structure and its quiescence is thought to reduce hippocampal seizure activity. This characteristic of the DG is also considered to be important for normal hippocampal-dependent cognitive functions. It has been suggested that the brain insults which cause epilepsy do so because they cause the DG to be more easily activated...
June 27, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28655644/pregnenolone-does-not-interfere-with-the-effects-of-cannabinoids-on-synaptic-transmission-in-the-cerebellum-and-the-nucleus-accumbens
#11
Anna Krohmer, Martin Brehm, Volker Auwärter, Bela Szabo
The steroid hormone pregnenolone attenuates several in vivo behavioural and somatic effects of the phytocannabinoid Δ(9)-tetrahydrocannabinol, and it was suggested that pregnenolone can protect the brain from cannabis intoxication. The primary neuronal cannabinoid action behind most of the behavioural and somatic effects of cannabinoids is presynaptic inhibition of synaptic transmission. Therefore, the hypothesis of the present study was that pregnenolone attenuates the inhibition of synaptic transmission elicited by cannabinoids...
June 24, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28655149/neuromodulation-of-axon-terminals
#12
Darpan Chakraborty, Dennis Q Truong, Marom Bikson, Hanoch Kaphzan
Understanding which cellular compartments are influenced during neuromodulation underpins any rational effort to explain and optimize outcomes. Axon terminals have long been speculated to be sensitive to polarization, but experimentally informed models for CNS stimulation are lacking. We conducted simultaneous intracellular recording from the neuron soma and axon terminal (blebs) during extracellular stimulation with weak sustained (DC) uniform electric fields in mouse cortical slices. Use of weak direct current stimulation (DCS) allowed isolation and quantification of changes in axon terminal biophysics, relevant to both suprathreshold (e...
June 24, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28649992/a-key-role-for-neurotensin-in-chronic-stress-induced-anxiety-like-behaviour-in-rats
#13
Catherine P Normandeau, Ana Paula Ventura Silva, Emily R Hawken, Staci Angelis, Calvin Sjaarda, Xudong Liu, José Miguel Pêgo, Éric C Dumont
Chronic stress is a major cause of anxiety disorders that can be reliably modeled pre-clinically, providing insight into alternative therapeutic targets for this mental health illness. Neuropeptides have been targeted in the past to no avail possibly due to our lack of understanding of their role in pathological models. In this study we use a rat model of chronic stress-induced anxiety-like behaviours and hypothesized that neuropeptidergic modulation of synaptic transmission would be altered in the Bed Nucleus of the Stria Terminalis (BNST), a brain region suspected to contribute to anxiety disorders...
June 26, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28635080/neuroadaptations-of-presynaptic-and-postsynaptic-gabab-receptor-function-in-the-paraventricular-nucleus-in-response-to-chronic-unpredictable-stress
#14
Yonggang Gao, Jing-Jing Zhou, Yun Zhu, Li Wang, Therese A Kosten, Xiangjian Zhang, De-Pei Li
BACKGROUND: Chronic stress induces an impaired GABAA (γ-aminobutyric acid type A) receptor-mediated inhibition in the hypothalamic paraventricular nucleus (PVN). It is not clear whether GABAB receptor function is altered in chronic stress. We hypothesize that chronic stress alters GABAB receptor function in PVN corticotrophin-releasing hormone (CRH) neurons to control hypothalamus-pituitary-adrenal (HPA) axis activity. EXPERIMENTAL APPROACH: Whole cell patch-clamp recording was performed on PVN-CRH neurons expressing eGFP driven by CRH promoter in brain slices from unstressed rats and rats that had been subjected to chronic unpredictable mild stress (CUMS)...
June 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28635024/a-small-molecule-activator-of-nav-1-1-channels-increases-fast-spiking-interneuron-excitability-and-gabaergic-transmission-in-vitro-and-has-anti-convulsive-effects-in-vivo
#15
Kristen Frederiksen, Lu Dunguo, Jinhui Yang, Henrik Sindal Jensen, Jesper Frank Bastlund, Peter Hjørringgaard Larsen, Liu Henry, Kim Dekermendjian, Lassina Badolo, Morten Laursen, Charlotte Hougaard, Charles Yang, Niels Svenstrup, Morten Grunnet
Nav 1.1 (SCN1A) channels primarily located in gamma-aminobutyric acid (GABA)ergic fast-spiking interneurons are pivotal for action potential generation and propagation in these neurons. Inappropriate function of fast-spiking interneurons, leading to disinhibition of pyramidal cells and network desynchronization, correlates with decreased cognitive capability. Further, reduced functionality of Nav 1.1 channels is linked to various diseases in the central nervous system. There is, at present, however no subtype selective pharmacological activators of Nav 1...
June 21, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28630662/sex-differences-in-endogenous-cortical-network-activity-spontaneously-recurring-up-down-states
#16
Charalambos Sigalas, Eleni Konsolaki, Irini Skaliora
BACKGROUND: Several molecular and cellular processes in the vertebrate brain exhibit differences between males and females, leading to sexual dimorphism in the formation of neural circuits and brain organization. While studies on large-scale brain networks provide ample evidence for both structural and functional sex differences, smaller-scale local networks have remained largely unexplored. In the current study, we investigate sexual dimorphism in cortical dynamics by means of spontaneous Up/Down states, a type of network activity that is exhibited during slow-wave sleep, quiet wakefulness, and anesthesia and is thought to represent the default activity of the cortex...
2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28629847/evidence-for-m2-muscarinic-receptor-modulation-of-axon-terminals-and-dendrites-in-the-rodent-basolateral-amygdala-an-ultrastructural-and-electrophysiological-analysis
#17
Ana Fajardo-Serrano, Lei Liu, David D Mott, Alexander J McDonald
The basolateral amygdala receives a very dense cholinergic innervation from the basal forebrain that is important for memory consolidation. Although behavioral studies have shown that both M1 and M2 muscarinic receptors are critical for these mnemonic functions, there have been very few neuroanatomical and electrophysiological investigations of the localization and function of different types of muscarinic receptors in the amygdala. In the present study we investigated the subcellular localization of M2 muscarinic receptors (M2Rs) in the anterior basolateral nucleus (BLa) of the mouse, including the localization of M2Rs in parvalbumin (PV) immunoreactive interneurons, using double-labeling immunoelectron microscopy...
June 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28625609/oxidative-stress-induced-by-cumene-hydroperoxide-produces-synaptic-depression-and-transient-hyperexcitability-in-rat-primary-motor-cortex-neurons
#18
R Pardillo-Diaz, L Carrascal, G Barrionuevo, P Nunez-Abades
Pyramidal neurons of the motor cortex are selectively degenerated in Amyotrophic Lateral Sclerosis (ALS). The mechanisms underlying neuronal death in ALS are not well established. In the absence of useful biomarkers, the early increased neuronal excitability seems to be the unique characteristic of ALS. Lipid peroxidation caused by oxidative stress has been postulated as one of the possible mechanisms involved in degeneration motor cortex pyramidal neurons. This paper examines the effect of lipid peroxidation on layer V pyramidal neurons induced by cumene hydroperoxide (CH) in brain slices from wild type rats...
June 15, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28624573/plasticity-of-intrinsic-firing-response-gain-in-principal-hippocampal-neurons-following-pilocarpine-induced-status-epilepticus
#19
Idit Tamir, Moshe Daninos, Yoel Yaari
OBJECTIVE: In experimental models of temporal lobe epilepsy (TLE), brain neurons manifest multiple changes in intrinsic excitability that contribute to neuronal network hyperexcitability. We have investigated whether the intrinsic firing response gain, quantified by the slope of the function relating the number of evoked spikes (Ns) to input excitatory current intensity (I), is modified in principal rat hippocampal neurons in the pilocarpine-status epilepticus (SE) model of TLE. METHODS: Intracellular recordings were made in CA3 and CA1 pyramidal cells (PCs) and dentate granule cells (GCs) in acute hippocampal slices obtained 7-36days after pilocarpine-SE...
June 15, 2017: Neuroscience
https://www.readbyqxmd.com/read/28604219/potentiation-of-nmda-receptor-mediated-synaptic-transmission-at-the-parabrachial-central-amygdala-synapses-by-cgrp-in-mice
#20
Yuya Okutsu, Yukari Takahashi, Masashi Nagase, Kei Shinohara, Ryo Ikeda, Fusao Kato
The capsular part of the central amygdala (CeC) is called the "nociceptive amygdala," as it receives nociceptive information from various pathways, including monosynaptic input from the lateral part of the parabrachial nucleus (LPB), a major target of ascending neurons in the spinal and medullary dorsal horn. LPB-CeC synaptic transmission is mediated by glutamate but the fibers from the LPB also contain calcitonin gene-related peptide (CGRP) and the CeC is rich in CGRP-binding sites. CGRP might be released in response to strong nociception and activate these CGRP receptors...
January 2017: Molecular Pain
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