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Anusha Mishra, James P Reynolds, Yang Chen, Alexander V Gourine, Dmitri A Rusakov, David Attwell
Active neurons increase their energy supply by dilating nearby arterioles and capillaries. This neurovascular coupling underlies blood oxygen level-dependent functional imaging signals, but its mechanism is controversial. Canonically, neurons release glutamate to activate metabotropic glutamate receptor 5 (mGluR5) on astrocytes, evoking Ca(2+) release from internal stores, activating phospholipase A2 and generating vasodilatory arachidonic acid derivatives. However, adult astrocytes lack mGluR5, and knockout of the inositol 1,4,5-trisphosphate receptors that release Ca(2+) from stores does not affect neurovascular coupling...
October 24, 2016: Nature Neuroscience
Alex Fogli Iseppe, Angela Pignatelli, Ottorino Belluzzi
Within the olfactory bulb (OB), periglomerular (PG) cells consist of various types of interneurons, generally classified by their chemical properties such as neurotransmitter and calcium binding proteins. Calretinin (CR) characterizes morphologically and functionally the more numerous and one of the less known subpopulation of PG cells in the OB. Using of transgenic mice expressing eGFP under the CR promoter, we have tried to obtain the first functional characterization of these cells. Electrophysiological recordings were made in these cells using the patch-clamp technique in thin slices...
2016: Frontiers in Cellular Neuroscience
Courtney L Huff, Rachel L Morano, James P Herman, Bryan K Yamamoto, Gary A Gudelsky
3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation...
October 20, 2016: Neurotoxicology
K R Sabitha, D Sanjay, B Savita, T R Raju, T R Laxmi
Neurons communicate with each other through intricate network to evolve higher brain functions. The electrical activity of the neurons plays a crucial role in shaping the connectivity. With motor neurons being vulnerable to neurodegenerative diseases, understanding the electrophysiological properties of motor neurons is the need of the hour, in order to comprehend the impairment of connectivity in these diseases. NSC-34 cell line serves as an excellent model to study the properties of motor neurons as they express Choline acetyltransferase (ChAT)...
November 15, 2016: Journal of the Neurological Sciences
Laila Y AlAyadhi, Jamil A Hashmi, Muhammad Iqbal, Alia M Albalawi, Mohammad I Samman, Nadra E Elamin, Shahid Bashir, Sulman Basit
Single nucleotide polymorphisms (SNP) - based genotyping using microarray platform is now frequently used to detect copy number variants (CNVs) in the human genome. Here, we report CNVs identified using Illumina HumanOmni 2.5 M oligonucleotide microarrays in 11 multiplex families with autism spectrum disorder (ASD) referred to Autism Research and Treatment Center (ART) and Madinah Maternity and Children Hospital (MMCH). Of the 11 families, 22 patients with ASD (all males) and their parents, were recruited for the present study...
October 19, 2016: Neuroscience
Simone A A Romariz, Daisyléa S Paiva, Layla T Galindo, Gabriela F Barnabé, Vivian A Guedes, Cesario V Borlongan, Beatriz M Longo
AIMS: Medial ganglionic eminence (MGE) progenitors give rise to inhibitory interneurons and may serve as an alternative cell source for large-scale cell transplantation for epilepsy after in vitro expansion. We investigated whether modifications in the culture medium of MGE neurospheres affect neuronal differentiation and expression of MGE-specific genes. In vivo, we compared anticonvulsant effects and cell differentiation pattern among neurospheres grown in different culture media and compared them with freshly harvested MGE cells...
October 21, 2016: CNS Neuroscience & Therapeutics
Franziska Richter, Julia Gerstenberger, Anne Bauer, Chun-Chi Liang, Angelika Richter
Hereditary generalized dystonia is often caused by a GAG deletion in TOR1A (DYT1) that encodes for the protein torsinA. Although mutation carriers show alterations in neuronal connectivity and sensorimotor deficits, only 30% develop dystonia. Uncovering the factors triggering the dystonic symptoms and underlying pathophysiology would greatly benefit the development of more effective therapies. In DYT1 knock-in (KI) mice, the expression of torsinA mutant alters the connectivity of neurons and the function of striatal cholinergic interneurons...
October 18, 2016: Behavioural Brain Research
Li-Wa Shao, Rong Niu, Ying Liu
Neurons have a central role in the systemic coordination of mitochondrial unfolded protein response (UPR(mt)) and the cell non-autonomous modulation of longevity. However, the mechanism by which the nervous system senses mitochondrial stress and communicates to the distal tissues to induce UPR(mt) remains unclear. Here we employ the tissue-specific CRISPR-Cas9 approach to disrupt mitochondrial function only in the nervous system of Caenorhabditis elegans, and reveal a cell non-autonomous induction of UPR(mt) in peripheral cells...
October 21, 2016: Cell Research
Andreas Arendt, El-Sayed Baz, Monika Stengl
The circadian pacemaker of the Madeira cockroach Rhyparobia (Leucophaea) maderae is located in the accessory medulla (AME). Ipsi- and contralateral histaminergic compound eyes are required for photic entrainment. Light pulses delayed locomotor activity rhythms during the early night and advanced during the late night. Thus, different neuronal pathways might relay either light-dependent delays or advances to the clock. Injections of neuroactive substances combined with running-wheel assays suggested that GABA, PDF, myoinhibitory peptides (MIPs), and orcokinins (ORCs) are part of both entrainment pathways, while allatotropin (AT) only delayed locomotor rhythms at the early night...
October 20, 2016: Journal of Comparative Neurology
Wei Bu, Huiling Ren, Yunping Deng, Nobel Del Mar, Natalie M Guley, Bob M Moore, Marcia G Honig, Anton Reiner
We have previously reported that mild TBI created by focal left-side cranial blast in mice produces widespread axonal injury, microglial activation, and a variety of functional deficits. We have also shown that these functional deficits are reduced by targeting microglia through their cannabinoid type-2 (CB2) receptors using 2-week daily administration of the CB2 inverse agonist SMM-189. CB2 inverse agonists stabilize the G-protein coupled CB2 receptor in an inactive conformation, leading to increased phosphorylation and nuclear translocation of the cAMP response element binding protein (CREB), and thus bias activated microglia from a pro-inflammatory M1 to a pro-healing M2 state...
2016: Frontiers in Neuroscience
Thomas J Younts, Hannah R Monday, Barna Dudok, Matthew E Klein, Bryen A Jordan, István Katona, Pablo E Castillo
Long-term changes of neurotransmitter release are critical for proper brain function. However, the molecular mechanisms underlying these changes are poorly understood. While protein synthesis is crucial for the consolidation of postsynaptic plasticity, whether and how protein synthesis regulates presynaptic plasticity in the mature mammalian brain remain unclear. Here, using paired whole-cell recordings in rodent hippocampal slices, we report that presynaptic protein synthesis is required for long-term, but not short-term, plasticity of GABA release from type 1 cannabinoid receptor (CB1)-expressing axons...
October 19, 2016: Neuron
Marie-Pascale Côté, Marion Murray, Michel A Lemay
Body-weight supported locomotor training (BWST) promotes recovery of load-bearing stepping in lower mammals, but its efficacy in individuals with a spinal cord injury (SCI) is limited and highly dependent on injury severity. While animal models with complete spinal transections recover stepping with step-training, motor complete SCI individuals do not, despite similarly intensive training. In this review, we examine the significant differences between humans and animal models that may explain this discrepancy in the results obtained with BWST...
October 20, 2016: Journal of Neurotrauma
Minhan Ka, Jeffrey J Moffat, Woo-Yang Kim
GABAergic interneurons develop in the ganglionic eminence in the ventral telencephalon and tangentially migrate into the cortical plate during development. However, key molecules controlling interneuron migration remain poorly identified. Here, we show that microtubule-actin cross-linking factor 1 (MACF1) regulates GABAergic interneuron migration and positioning in the developing mouse brain. To investigate the role of MACF1 in developing interneurons, we conditionally deleted the MACF1 gene in mouse interneuron progenitors and their progeny using Dlx5/6-Cre-IRES-EGFP and Nkx2...
October 18, 2016: Cerebral Cortex
K M Naga Srinivas Nadella, Hana Roš, Chiara Baragli, Victoria A Griffiths, George Konstantinou, Theo Koimtzis, Geoffrey J Evans, Paul A Kirkby, R Angus Silver
Understanding how neural circuits process information requires rapid measurements of activity from identified neurons distributed in 3D space. Here we describe an acousto-optic lens two-photon microscope that performs high-speed focusing and line scanning within a volume spanning hundreds of micrometers. We demonstrate its random-access functionality by selectively imaging cerebellar interneurons sparsely distributed in 3D space and by simultaneously recording from the soma, proximal and distal dendrites of neocortical pyramidal cells in awake behaving mice...
October 17, 2016: Nature Methods
Jianing Yu, Diego A Gutnisky, S Andrew Hires, Karel Svoboda
We rely on movement to explore the environment, for example, by palpating an object. In somatosensory cortex, activity related to movement of digits or whiskers is suppressed, which could facilitate detection of touch. Movement-related suppression is generally assumed to involve corollary discharges. Here we uncovered a thalamocortical mechanism in which cortical fast-spiking interneurons, driven by sensory input, suppress movement-related activity in layer 4 (L4) excitatory neurons. In mice locating objects with their whiskers, neurons in the ventral posteromedial nucleus (VPM) fired in response to touch and whisker movement...
October 17, 2016: Nature Neuroscience
Iryna Yavorska, Michael Wehr
Cortical inhibitory neurons exhibit remarkable diversity in their morphology, connectivity, and synaptic properties. Here, we review the function of somatostatin-expressing (SOM) inhibitory interneurons, focusing largely on sensory cortex. SOM neurons also comprise a number of subpopulations that can be distinguished by their morphology, input and output connectivity, laminar location, firing properties, and expression of molecular markers. Several of these classes of SOM neurons show unique dynamics and characteristics, such as facilitating synapses, specific axonal projections, intralaminar input, and top-down modulation, which suggest possible computational roles...
2016: Frontiers in Neural Circuits
Dohoung Kim, Huijeong Jeong, Juhyeong Lee, Jeong-Wook Ghim, Eun Sil Her, Seung-Hee Lee, Min Whan Jung
Inhibitory interneurons are thought to play crucial roles in diverse brain functions. However, roles of different inhibitory interneuron subtypes in working memory remain unclear. We found distinct activity patterns and stimulation effects of two major interneuron subtypes, parvalbumin (PV)- and somatostatin (SOM)-expressing interneurons, in the medial prefrontal cortex of mice performing a spatial working memory task. PV interneurons showed weak target-dependent delay-period activity and were strongly inhibited by reward...
October 12, 2016: Neuron
Katarzyna Lebida, Jerzy W Mozrzymas
Experience and learning in adult primary somatosensory cortex are known to affect neuronal circuits by modifying both excitatory and inhibitory transmission. Synaptic plasticity phenomena provide a key substrate for cognitive processes, but precise description of the cellular and molecular correlates of learning is hampered by multiplicity of these mechanisms in various projections and in different types of neurons. Herein, we investigated the impact of associative learning on neuronal plasticity in distinct types of postsynaptic neurons by checking the impact of classical conditioning (pairing whisker stroking with tail shock) on the spike timing-dependent plasticity (t-LTP and t-LTD) in the layer IV to II/III vertical pathway of the mouse barrel cortex...
October 15, 2016: Molecular Neurobiology
Helena Soler, Jonatan Dorca-Arévalo, Marta González, Sara Esmeralda Rubio, Jesús Ávila, Eduardo Soriano, Marta Pascual
Alzheimer's disease (AD), the most common cause of dementia nowadays, has been linked to alterations in the septohippocampal pathway (SHP), among other circuits in the brain. In fact, the GABAergic component of the SHP, which controls hippocampal rhythmic activity crucial for learning and memory, is altered in the J20 mouse model of AD-a model that mimics the amyloid pathology of this disease. However, AD is characterized by another pathophysiological hallmark: the hyperphosphorylation and aggregation of the microtubule-associated protein Tau...
September 15, 2016: Neurobiology of Aging
Nelly Redolfi, Luisa Galla, Andrea Maset, Luca Murru, Eleonora Savoia, Ilaria Zamparo, Angela Gritti, Pierre Billuart, Maria Passafaro, Claudia Lodovichi
Among the X-linked genes associated to intellectual disability, Oligophrenin-1 (OPHN1) encodes for a Rho GTPase-activating protein, a key regulator of several developmental processes, such as dendrite and spine formation and synaptic activity. Inhibitory interneurons play a key role in the development and function of neuronal circuits. Whether mutation of OPHN1 can affect morphology and synaptic properties of inhibitory interneurons remains poorly understood. To address these open questions, we studied in a well established mouse model of X-linked intellectual disability, i...
October 13, 2016: Human Molecular Genetics
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