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Interneuron AND Hippocampus

Christin Weissleder, Hayley F North, Cynthia Shannon Weickert
PURPOSE OF REVIEW: Aberrant neurogenesis may contribute to the pathogenesis, pathophysiology and symptoms of schizophrenia. This review summarizes the state of knowledge of adult neurogenesis in schizophrenia and raises important unanswered questions. We highlight how alterations in signalling molecules in the local and peripheral environments in schizophrenia may regulate adult neurogenesis in the human subgranular zone of the hippocampus and the subependymal zone (SEZ). RECENT FINDINGS: Cell proliferation and density of mature neurons are reduced in the hippocampus, yet the extent of adult neurogenesis remains unexplored in the SEZ in schizophrenia...
February 12, 2019: Current Opinion in Psychiatry
Junghee Jin, Dionnet L Bhatti, Ko-Woon Lee, Lucian Medrihan, Jia Cheng, Jing Wei, Ping Zhong, Zhen Yan, Cassandra Kooiker, Claire Song, Jung-Hyuck Ahn, Gerald J Obermair, Amy Lee, Jodi Gresack, Paul Greengard, Yong Kim
Genetic polymorphisms of the L-type voltage-gated calcium channel (VGCC) are associated with psychiatric disorders including major depressive disorder. Alterations of S100A10 (p11) level are also implicated in the etiology of major depressive disorder. However, the existence of an endogenous regulator in the brain regulating p11, L-type VGCC, and depressive behavior has not been known. Here we report that Ahnak, whose function in the brain has been obscure, stabilizes p11 and Anxa2 proteins in the hippocampus and prefrontal cortex in the rodent brain...
February 13, 2019: Molecular Psychiatry
Gergely Farkas Turi, Wen-Ke Li, Spyridon Chavlis, Ioanna Pandi, Justin O'Hare, James Benjamin Priestley, Andres Daniel Grosmark, Zhenrui Liao, Max Ladow, Jeff Fang Zhang, Boris Valery Zemelman, Panayiota Poirazi, Attila Losonczy
Diverse computations in the neocortex are aided by specialized GABAergic interneurons (INs), which selectively target other INs. However, much less is known about how these canonical disinhibitory circuit motifs contribute to network operations supporting spatial navigation and learning in the hippocampus. Using chronic two-photon calcium imaging in mice performing random foraging or goal-oriented learning tasks, we found that vasoactive intestinal polypeptide-expressing (VIP+ ), disinhibitory INs in hippocampal area CA1 form functional subpopulations defined by their modulation by behavioral states and task demands...
January 18, 2019: Neuron
Md Mamun Al-Amin, Robert K P Sullivan, Nyoman D Kurniawan, Thomas H J Burne
Converging evidence from human and animal studies support an association between vitamin D deficiency and cognitive impairment. Previous studies have shown that hippocampal volume is reduced in adults with vitamin D deficiency as well as in a range of disorders, such as schizophrenia. The aim of the current study was to examine the effect of adult vitamin D (AVD) deficiency on hippocampal-dependent spatial learning, and hippocampal volume and connectivity in healthy adult mice. Ten-week-old male BALB/c mice were fed a control (vitamin D 1500 IU/kg) or vitamin D-depleted (vitamin D 0 IU/kg) diet for a minimum of 10 weeks...
February 2, 2019: Brain Structure & Function
Felipe V Gomes, Xiyu Zhu, Anthony A Grace
Schizophrenia is a neurodevelopmental disorder with genetic predisposition, and stress has long been linked to its etiology. While stress affects all stages of the illness, increasing evidence suggests that stress during critical periods of development may be particularly detrimental, increasing individual's vulnerability to psychosis. To thoroughly understand the potential causative role of stress, our group has been focusing on the prenatal methylazoxymethanol acetate (MAM) rodent model, and discovered that MAM offspring display abnormal stress reactivity and heightened anxiety prepubertally, prior to the manifestation of a hyperdopaminergic state...
January 30, 2019: Schizophrenia Research
S Alaiyed, P L Bozzelli, A Caccavano, J Y Wu, K Conant
Drugs that target monoaminergic transmission represent a first-line treatment for major depression. Though a full understanding of the mechanisms that underlie antidepressant efficacy is lacking, evidence supports a role for enhanced excitatory transmission. This can occur through two non-mutually exclusive mechanisms. The first involves increased function of excitatory neurons through relatively direct mechanisms such as enhanced dendritic arborization. Another mechanism involves reduced inhibitory function, which occurs with the rapid antidepressant ketamine...
January 30, 2019: Journal of Neurochemistry
Hiroyuki Miyawaki, Brendon O Watson, Kamran Diba
Neurons fire at highly variable intrinsic rates and recent evidence suggests that low- and high-firing rate neurons display different plasticity and dynamics. Furthermore, recent publications imply possibly differing rate-dependent effects in hippocampus versus neocortex, but those analyses were carried out separately and with potentially important differences. To more effectively synthesize these questions, we analyzed the firing rate dynamics of populations of neurons in both hippocampal CA1 and frontal cortex under one framework that avoids the pitfalls of previous analyses and accounts for regression to the mean (RTM)...
January 24, 2019: Scientific Reports
Giovanna Paolone, Chiara Falcicchia, Francesca Lovisari, Merab Kokaia, William J Bell, Tracie Fradet, Mario Barbieri, Lars U Wahlberg, Dwaine F Emerich, Michele Simonato
Neurotrophic factors are candidates for treating epilepsy but their development has been hampered by difficulties in achieving stable and targeted delivery of efficacious concentrations within the desired brain region. We have developed an encapsulated cell technology that overcomes these obstacles by providing a targeted, continuous, de novo synthesized source of high levels of neurotrophic molecules from human clonal ARPE-19 cells encapsulated into hollow fiber membranes. Here we illustrate the potential of this approach for delivering glial cell line-derived neurotrophic factor (GDNF) directly to the hippocampus of epileptic rats...
January 21, 2019: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Zoe Noakes, Francesca Keefe, Claudia Tamburini, Claire M Kelly, Maria Cruz Santos, Stephen B Dunnett, Adam C Errington, Meng Li
Striatal interneurons are born in the medial and caudal ganglionic eminences (MGE and CGE) and play an important role in human striatal function and dysfunction in Huntington's disease and dystonia. MGE/CGE-like neural progenitors have been generated from human pluripotent stem cells (hPSCs) for studying cortical interneuron development and cell therapy for epilepsy and other neurodevelopmental disorders. Here, we report the capacity of hPSC-derived MGE/CGE-like progenitors to differentiate into functional striatal interneurons...
February 12, 2019: Stem Cell Reports
Raphaële Mongrédien, Amaia M Erdozain, Sylvie Dumas, Laura Cutando, Amaia Nuñez Del Moral, Emma Puighermanal, Sara Rezai Amin, Bruno Giros, Emmanuel Valjent, J Javier Meana, Sophie Gautron, Luis F Callado, Véronique Fabre, Vincent Vialou
Hevin, also known as SPARC-like 1, is a member of the secreted protein acidic and rich in cysteine family of matricellular proteins, which has been implicated in neuronal migration and synaptogenesis during development. Unlike previously characterized matricellular proteins, hevin remains strongly expressed in the adult brain in both astrocytes and neurons, but its precise pattern of expression is unknown. The present study provides the first systematic description of hevin mRNA distribution in the adult mouse brain...
January 17, 2019: Brain Structure & Function
Jan-Oliver Hollnagel, Shehabeldin Elzoheiry, Karin Gorgas, Stefan Kins, Carlo Antonio Beretta, Joachim Kirsch, Jochen Kuhse, Oliver Kann, Eva Kiss
Several lines of evidence imply changes in inhibitory interneuron connectivity and subsequent alterations in oscillatory network activities in the pathogenesis of Alzheimer's Disease (AD). Recently, we provided evidence for an increased immunoreactivity of both the postsynaptic scaffold protein gephyrin and the GABAA receptor γ2-subunit in the hippocampus of young (1 and 3 months of age), APPPS1 mice. These mice represent a well-established model of cerebral amyloidosis, which is a hallmark of human AD. In this study, we demonstrate a robust increase of parvalbumin immunoreactivity and accentuated projections of parvalbumin positive (PV+) interneurons, which target perisomatic regions of pyramidal cells within the hippocampal subregions CA1 and CA3 of 3-month-old APPPS1 mice...
2019: PloS One
Rocío Alfaro-Ruíz, Carolina Aguado, Alejandro Martín-Belmonte, Ana Esther Moreno-Martínez, Rafael Luján
The Kv4 family of voltage-gated K⁺ channels underlie the fast transient (A-type) outward K⁺ current. Although A-type currents are critical to determine somato-dendritic integration in central neurons, relatively little is known about the precise subcellular localisation of the underlying channels in hippocampal circuits. Using histoblot and immunoelectron microscopic techniques, we investigated the expression, regional distribution and subcellular localisation of Kv4.2 and Kv4.3 in the adult brain, as well as the ontogeny of their expression during postnatal development...
January 9, 2019: International Journal of Molecular Sciences
Alexandre Guet-McCreight, Frances K Skinner
Brain coding strategies are enabled by the balance of synaptic inputs that individual neurons receive as determined by the networks in which they reside. Inhibitory cell types contribute to brain function in distinct ways but recording from specific, inhibitory cell types during behaviour to determine their contributions is highly challenging. In particular, the in vivo activities of vasoactive intestinal peptide-expressing interneuron specific 3 (IS3) cells in the hippocampus that only target other inhibitory cells are unknown at present...
2019: PloS One
Benjamin Svejgaard, Mogens Andreasen, Steen Nedergaard
The mechanisms underlying antiepileptic effects of deep brain stimulation (DBS) are complex and poorly understood. Studies on the effects of applied electric fields on epileptic nervous tissue could enable future advances in DBS treatments. Applied electric fields are known to inhibit or enhance epileptic activity in vitro through direct effects on local neurons, but it is unclear whether trans-synaptic effects participate in such actions. The present study investigated, in an epileptic brain slice model, the influence of GABAB receptor activation on excitatory and suppressive effects of a short-duration (10 ms) electric field in rat hippocampus...
December 29, 2018: Brain Research
Dinesh Upadhya, Bharathi Hattiangady, Olagide W Castro, Bing Shuai, Maheedhar Kodali, Sahithi Attaluri, Adrian Bates, Yi Dong, Su-Chun Zhang, Darwin J Prockop, Ashok K Shetty
Medial ganglionic eminence (MGE)-like interneuron precursors derived from human induced pluripotent stem cells (hiPSCs) are ideal for developing patient-specific cell therapy in temporal lobe epilepsy (TLE). However, their efficacy for alleviating spontaneous recurrent seizures (SRS) or cognitive, memory, and mood impairments has never been tested in models of TLE. Through comprehensive video- electroencephalographic recordings and a battery of behavioral tests in a rat model, we demonstrate that grafting of hiPSC-derived MGE-like interneuron precursors into the hippocampus after status epilepticus (SE) greatly restrained SRS and alleviated cognitive, memory, and mood dysfunction in the chronic phase of TLE...
January 2, 2019: Proceedings of the National Academy of Sciences of the United States of America
Hartmut T Bocker, Theresa Heinrich, Lutz Liebmann, J Christopher Hennings, Eric Seemann, Melanie Gerth, Igor Jakovcevski, Julia Preobraschenski, Michael M Kessels, Martin Westermann, Dirk Isbrandt, Reinhard Jahn, Britta Qualmann, Christian A Hübner
Brain functions are extremely sensitive to pH changes because of the pH-dependence of proteins involved in neuronal excitability and synaptic transmission. Here, we show that the Na+/H+ exchanger Nhe1, which uses the Na+ gradient to extrude H+, is expressed at both inhibitory and excitatory presynapses. We disrupted Nhe1 specifically in mice either in Emx1-positive glutamatergic neurons or in parvalbumin-positive cells, mainly GABAergic interneurons. While Nhe1 disruption in excitatory neurons had no effect on overall network excitability, mice with disruption of Nhe1 in parvalbumin-positive neurons displayed epileptic activity...
December 12, 2018: Cerebral Cortex
Nichola Marie Brydges, Anna Moon, Lowenna Rule, Holly Watkin, Kerrie L Thomas, Jeremy Hall
Experience of traumatic events in childhood is linked to an elevated risk of developing psychiatric disorders in adulthood. The neurobiological mechanisms underlying this phenomenon are not fully understood. The limbic system, particularly the hippocampus, is significantly impacted by childhood trauma. In particular, it has been hypothesised that childhood stress may impact adult hippocampal neurogenesis (AHN) and related behaviours, conferring increased risk for later mental illness. Stress in utero can lead to impaired hippocampal synaptic plasticity, and stress in the first 2-3 weeks of life reduces AHN in animal models...
December 10, 2018: Translational Psychiatry
Georgia Economides, Svenja Falk, Audrey Mercer
How cortical network activity processes information is of importance to a large number of basic and clinical scientific questions. The protocol described here identifies the basic building blocks of this circuitry. The in-depth studies of cortical regions will ultimately provide other scientists with the circuit components needed for an understanding of how the brain acquires, processes and stores information and what goes wrong in disease, while the electrophysiological and morphological data are widely used by computational neuroscientists in the construction of model networks that explore information processing...
November 20, 2018: Journal of Visualized Experiments: JoVE
Elise Magnin, Ruggiero Francavilla, Sona Amalyan, Etienne Gervais, Linda Suzanne David, Xiao Luo, Lisa Topolnik
Hippocampus-dependent learning processes are coordinated via a large diversity of GABAergic inhibitory mechanisms. The alpha5 subunit-containing GABAA receptor (α5-GABAA R) is abundantly expressed in the hippocampus populating primarily the extrasynaptic domain of CA1 pyramidal cells, where it mediates tonic inhibitory conductance and may cause functional deficits in synaptic plasticity and hippocampus-dependent memory. However, little is known about synaptic expression of the α5-GABAA R and, accordingly, its location site-specific function...
December 6, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Yuki Hashimotodani, Fuyuki Karube, Yuchio Yanagawa, Fumino Fujiyama, Masanobu Kano
The supramammillary nucleus (SuM) of the hypothalamus projects to the dentate gyrus (DG) and the CA2 region of the hippocampus. Although the SuM-to-hippocampus circuits have been implicated in spatial and emotional memory formation, little is known about precise neural connections between the SuM and hippocampus. Here, we report that axons of SuM neurons make monosynaptic connections to granule cells (GCs) and GABAergic interneurons, but not to hilar mossy cells, in the DG and co-release glutamate and γ-aminobutyric acid (GABA) at these synapses...
December 4, 2018: Cell Reports
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