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Interneuron AND Hippocampus

Muhammad Tahir Khan, Jan Deussing, Yong Tang, Peter Illes
Whole-cell patch clamp recordings demonstrated that in the dentate gyrus (DG) as well as in the CA3 area of mouse hippocampal slices the prototypic P2 × 7 receptor (R) agonist dibenzoyl-ATP (Bz-ATP) induced inward current responses both in neurons and astrocytes. Whereas the selective P2 × 7R antagonist A438079 strongly inhibited both neuronal and astrocytic currents, a combination of ionotropic glutamate receptor (CNQX, AP-5) and GABAA -R (gabazine) antagonists depressed the Bz-ATP-induced current responses in the DG (granule cells) and CA3 neurons only...
August 8, 2018: Brain Research Bulletin
Tamara K Stevenson, Daniel A Lawrence
Tissue plasminogen activator (tPA) is an immediate-early gene important for regulating physiological processes like synaptic plasticity and neurovascular coupling. It has also been implicated in several pathological processes including blood-brain barrier (BBB) permeability, seizure progression, and stroke. These varied reports suggest that tPA is a pleiotropic mediator whose actions are highly compartmentalized in space and time. The specific localization of tPA, therefore, can provide useful information about its function...
July 2018: ENeuro
Laverne C Melón, James T Nasman, Ashley St John, Kenechukwu Mbonu, Jamie L Maguire
Extensive evidence points to a role for GABAergic signaling in the amygdala in mediating the effects of alcohol, including presynaptic changes in GABA release, suggesting effects on GABAergic neurons. However, the majority of studies focus solely on the effects of alcohol on principal neurons. Here we demonstrate that δ-GABAA Rs, which have been suggested to confer ethanol sensitivity, are expressed at a high density on parvalbumin (PV) interneurons in the basolateral amygdala (BLA). Thus, we hypothesized that δ-GABAA Rs on PV interneurons may represent both an initial pharmacological target for alcohol and a site for plasticity associated with the expression of various behavioral maladaptations during withdrawal from binge drinking...
July 28, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Simone F Carron, Edwin B Yan, Benjamin J Allitt, Ramesh Rajan
Changes in inhibition following traumatic brain injury (TBI) appear to be one of the major factors that contribute to excitation:inhibition imbalance. Neuron pathology, interneurons in particular evolves from minutes to weeks post injury and follows a complex time course. Previously, we showed that in the long-term in diffuse TBI (dTBI), there was select reduction of specific dendrite-targeting neurons in sensory cortex and hippocampus while in motor cortex there was up-regulation of specific dendrite-targeting neurons...
July 21, 2018: Neuroscience
Hiroo Takahashi, Seiichi Yoshihara, Akio Tsuboi
It has been shown in a variety of mammalian species that sensory experience can regulate the development of various structures, including the retina, cortex, hippocampus, and olfactory bulb (OB). In the mammalian OB, the development of dendrites in excitatory projection neurons, such as mitral and tufted cells, is well known to be dependent on odor experience. Odor experience is also involved in the development of another OB population, a subset of inhibitory interneurons that are generated in the ventricular-subventricular zone throughout life and differentiate into granule cells (GCs) and periglomerular cells...
2018: Frontiers in Molecular Neuroscience
Katelynn M Corder, Mariana A Cortes, Aundrea F Bartley, Samantha A Lear, Farah D Lubin, Lynn E Dobrunz
GABAergic dysfunction has been implicated in a variety of neurological and psychiatric disorders, including anxiety disorders. Anxiety disorders are the most common type of psychiatric disorder during adolescence. There is a deficiency of GABAergic transmission in anxiety, and enhancement of GABA transmission through pharmacological means reduces anxiety behaviors. GAD67-the enzyme responsible for GABA production-has been linked to anxiety disorders. One class of GABAergic interneurons, Neuropeptide Y (NPY) expressing cells, is abundantly found in brain regions associated with anxiety and fear learning, including prefrontal cortex, hippocampus and amygdala...
2018: PloS One
Marta Zagrebelsky, N Gödecke, A Remus, Martin Korte
Brain-derived neurotrophin factor (BDNF) has been implicated in neuronal survival, differentiation and activity-dependent synaptic plasticity in the central nervous system. It was suggested that during postnatal development BDNF regulates neuronal architecture and spine morphology of neurons within certain brain areas but not others. Particularly striking are the differences between striatum, cortex and hippocampus. Whether this is due to region- or cell type-specific effects is so far not known. We address this question using conditional bdnf knock-out mice to analyze neuronal architecture and spine morphology of pyramidal cortical and hippocampal neurons as well as inhibitory neurons from these brain areas and excitatory granule neurons from the dentate gyrus...
July 18, 2018: Brain Structure & Function
Hector Carceller, Marta Perez-Rando, Eero Castren, Juan Nacher, Ramon Guirado
Although the precise mechanism of action of antidepressant drugs remains elusive, the neuroplastic hypothesis has gained acceptance during the last two decades. Several studies have shown that treatment with antidepressants such as Fluoxetine is associated with enhanced plasticity in control animals, especially in regions such as the visual cortex, the hippocampus and the medial prefrontal cortex. More recently, the basolateral amygdala has been shown to be affected by Fluoxetine leading to a reopening of critical period-like plasticity in the fear and aggression circuits...
August 21, 2018: Neuroscience
Rigil K Yeung, Zheng-Hua Xiang, Shui-Ying Tsang, Rui Li, Timothy Y C Ho, Qi Li, Chok-King Hui, Pak-Chung Sham, Ming-Qi Qiao, Hong Xue
Intronic polymorphisms of the GABAA receptor β2 subunit gene (GABRB2) under adaptive evolution were associated with schizophrenia and reduced expression, especially of the long isoform which differs in electrophysiological properties from the short isoform. The present study was directed to examining the gene dosage effects of Gabrb2 in knockout mice of both heterozygous (HT) and homozygous (KO) genotypes with respect to possible schizophrenia-like and comorbid phenotypes. The KO mice, and HT mice to a lesser extent, were found to display prepulse inhibition (PPI) deficit, locomotor hyperactivity, stereotypy, sociability impairments, spatial-working and spatial-reference memory deficits, reduced depression and anxiety, and accelerated pentylenetetrazol (PTZ)-induced seizure...
July 17, 2018: Translational Psychiatry
Edit Szodorai, Konstantina Bampali, Roman A Romanov, Siegfried Kasper, Tomas Hökfelt, Margot Ernst, Gert Lubec, Tibor Harkany
In the hippocampus, GABA inhibition tunes network oscillations and shapes synchronous activity during spatial learning and memory coding. Once released from the presynapse, GABA primarily binds to ionotropic GABAA receptors (GABAA Rs), which are heteropentamers combinatorially assembled from nineteen known subunits to induce Cl- currents postsynaptically. Dissecting GABAA R subtype specificities in neurobiology is daunting because of differences in their developmental dynamics, regional distribution and subcellular compartmentalization...
October 2018: Cellular Signalling
Rafael Falcón-Moya, Talvinder S Sihra, Antonio Rodríguez-Moreno
Kainate (KA) is a potent neurotoxin that has been widely used experimentally to induce acute brain seizures and, after repetitive treatments, as a chronic model of temporal lobe epilepsy (TLE), with similar features to those observed in human patients with TLE. However, whether KA activates KA receptors (KARs) as an agonist to mediate the induction of acute seizures and/or the chronic phase of epilepsy, or whether epileptogenic effects of the neurotoxin are indirect and/or mediated by other types of receptors, has yet to be satisfactorily elucidated...
2018: Frontiers in Molecular Neuroscience
Aurore Curie, Gaëlle Friocourt, Vincent des Portes, Alice Roy, Tatjana Nazir, Amandine Brun, Anne Cheylus, Pascale Marcorelles, Kalliroi Retzepi, Nasim Maleki, Gérald Bussy, Yves Paulignan, Anne Reboul, Danielle Ibarrola, Jian Kong, Nouchine Hadjikhani, Annie Laquerrière, Randy L Gollub
The ARX ( Aristaless Related homeoboX ) gene was identified in 2002 as responsible for XLAG syndrome, a lissencephaly characterized by an almost complete absence of cortical GABAergic interneurons, and for milder forms of X-linked Intellectual Disability (ID) without apparent brain abnormalities. The most frequent mutation found in the ARX gene, a duplication of 24 base pairs (c.429_452dup24) in exon 2, results in a recognizable syndrome in which patients present ID without primary motor impairment, but with a very specific upper limb distal motor apraxia associated with a pathognomonic hand-grip, described as developmental Limb Kinetic Apraxia (LKA)...
2018: NeuroImage: Clinical
Jacqueline E McDermott, Dena Goldblatt, Suzanne Paradis
To understand how proper circuit formation and function is established in the mammalian brain, it is necessary to define the genes and signaling pathways that instruct excitatory and inhibitory synapse development. We previously demonstrated that the ligand-receptor pair, Sema4D and Plexin-B1, regulates inhibitory synapse development on an unprecedentedly fast time-scale while having no effect on excitatory synapse development. Here, we report previously undescribed synaptogenic roles for Sema4A and Plexin-B2 and provide new insight into Sema4D and Plexin-B1 regulation of synapse development in rodent hippocampus...
July 4, 2018: Molecular and Cellular Neurosciences
Camilla Boschian, Andrea Messina, Angela Bozza, Maria Elena Castellini, Giovanni Provenzano, Yuri Bozzi, Simona Casarosa
The Engrailed-2 (En2) gene codes for a homeobox-containing transcription factor, involved in midbrain-hindbrain embryonic development. In postnatal brain, En2 is expressed in the ventral mesencephalon, cerebellum, hippocampus and neocortex. Two single-nucleotide polymorphisms (SNPs) that are associated to autism spectrum disorders (ASD) have been identified in the human EN2 gene. Accordingly, mice lacking the En2 homeodomain (En2hd/hd , referred to as En2-/- ) show molecular, anatomical and behavioral "ASD-like" features...
June 30, 2018: Neuroscience
Gubbi Govindaiah, Young-Jin Kang, Hannah Elisabeth Smashey Lewis, Leeyup Chung, Ethan M Clement, Lazar John Greenfield, Edgar Garcia-Rill, Sang-Hun Lee
GABAergic interneurons in the hippocampus are critically involved in almost all hippocampal circuit functions including coordinated network activity. Somatostatin-expressing oriens-lacunosum moleculare (O-LM) interneurons are a major subtype of dendritically projecting interneurons in hippocampal subregions (e.g., CA1), and express group I metabotropic glutamate receptors (mGluRs), specifically mGluR1 and mGluR5 . Group I mGluRs are thought to regulate hippocampal circuit functions partially through GABAergic interneurons...
September 1, 2018: Neuropharmacology
Lam Son Nguyen, Julien Fregeac, Christine Bole-Feysot, Nicolas Cagnard, Anand Iyer, Jasper Anink, Eleonora Aronica, Olivier Alibeu, Patrick Nitschke, Laurence Colleaux
Background: MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression at the post-transcriptional level. miRNAs have emerged as important modulators of brain development and neuronal function and are implicated in several neurological diseases. Previous studies found miR-146a upregulation is the most common miRNA deregulation event in neurodevelopmental disorders such as autism spectrum disorder (ASD), epilepsy, and intellectual disability (ID). Yet, how miR-146a upregulation affects the developing fetal brain remains unclear...
2018: Molecular Autism
Giulia Quattrocolo, Maria Isaac, Yajun Zhang, Timothy J Petros
Neuronal fate determination and maturation requires an intricate interplay between genetic programs and environmental signals. However, disentangling the roles of intrinsic vs. extrinsic mechanisms that regulate this differentiation process is a conundrum for all developmental neurobiologists. This issue is magnified for GABAergic interneurons, an incredibly heterogeneous cell population that is born from transient embryonic structures and undergo a protracted migratory phase to disperse throughout the telencephalon...
June 8, 2018: Journal of Visualized Experiments: JoVE
Asghar Talebian, Rachel Britton, Mark Henkemeyer
To explore roles for ephrin-B/EphB signaling in cortical interneurons, we previously generated ephrin-B (Efnb1/b2/b3) conditional triple mutant (TMlz ) mice using a Dlx1/2.Cre inhibitory neuron driver and green fluorescent protein (GFP) reporters for the two main inhibitory interneuron groups distinguished by expression of either glutamic acid decarboxylase 1 (GAD1; GAD67-GFP) or 2 (GAD2; GAD65-GFP). This work showed a general involvement of ephrin-B in migration and population of interneurons into the embryonic neocortex...
June 14, 2018: European Journal of Neuroscience
Hussam Hayani, Inseon Song, Alexander Dityatev
The neural extracellular matrix (ECM) is enriched with hyaluronic acid, chondroitin sulfate proteoglycans (CSPGs) and the glycoprotein tenascin-R, which play important roles in synaptic plasticity, as shown by studies of the CA1 region of the hippocampus. However, ECM molecules are strongly expressed in the CA2 region, which harbors a high number of fast-spiking interneurons (FSIs) surrounded by a particularly condensed form of ECM, perineuronal nets. Despite this intriguing peculiarity, the functional role of ECM in the CA2 region is mostly unknown...
2018: Frontiers in Cellular Neuroscience
Tatsuya Katahira, Naoko Miyazaki, Jun Motoyama
Aversive experiences, including maternal separation (MS), have been known as a risk for abnormal hippocampus development. Given that impairment of GABA inhibitory system is known as one of the common features of the abnormal hippocampal development induced by MS, we examined whether the MS on 4-day-old (P4) mice for 24 hr abolishes the interneuron development. We observed that the MS reduced the volume of dorsal hippocampus on P14 as long-term effects. In addition, the MS decreased the number of parvalbumin (PV)-positive interneuron on P14 and P28 in the dorsal hippocampus...
June 2018: Development, Growth & Differentiation
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