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Interneuron AND Hippocampus

Nickesha C Anderson, Meghan A Van Zandt, Swechhya Shrestha, Daniel B Lawrence, Jyoti Gupta, Christopher Y Chen, Felicia A Harrsch, Trinithas Boyi, Carolyn E Dundes, Gloster Aaron, Janice R Naegele, Laura Grabel
GABAergic interneuron dysfunction has been implicated in temporal lobe epilepsy (TLE), autism, and schizophrenia. Inhibitory interneuron progenitors transplanted into the hippocampus of rodents with TLE provide varying degrees of seizure suppression. We investigated whether human embryonic stem cell (hESC)-derived interneuron progenitors (hESNPs) could differentiate, correct hippocampal-dependent spatial memory deficits, and suppress seizures in a pilocarpine-induced TLE mouse model. We found that transplanted ventralized hESNPs differentiated into mature GABAergic interneurons and became electrophysiologically active with mature firing patterns...
October 5, 2018: Stem Cell Research
Heng Zhang, Xiao He, Yufei Mei, Qingzhou Ling
Parvalbumin (PV) positive interneurons in the subgranular zone (SGZ) can regulate adult hippocampal neurogenesis. ErbB4 is mainly expressed in PV neurons in the hippocampus and is crucial for keeping normal function of PV neurons. However, whether ErbB4 in PV interneurons affects the adult hippocampal neurogenesis remains unknown. In the present study, we deleted ErbB4 specifically in PV neurons by crossing PV-Cre mice with ErbB4f/f mice. Results of BrdU labeling and NeuN staining revealed that the proliferation of neural progenitors was increased but the survival and maturation of newborn neurons were decreased in the hippocampus of mice after deleting ErbB4 in PV neurons, suggesting that ErbB4 in PV neurons is closely associated with the process of adult hippocampal neurogenesis...
October 17, 2018: Journal of Comparative Neurology
Fiorenza Stagni, Andrea Giacomini, Marco Emili, Beatrice Uguagliati, Maria Paola Bonasoni, Renata Bartesaghi, Sandra Guidi
Intellectual disability in Down syndrome (DS) has been attributed to neurogenesis impairment during fetal brain development. Consistently with explicit memory alterations observed in children with DS, fetuses with DS exhibit neurogenesis impairment in the hippocampus, a key region involved in memory formation and consolidation. Recent evidence suggests that the subiculum plays a unique role in memory retrieval, a process that is also altered in DS. While much attention has been devoted to the hippocampus, there is a striking lack of information regarding the subiculum of individuals with DS and DS models...
October 16, 2018: Brain Pathology
Diana Yae Sakae, Lauriane Ramet, Annabelle Henrion, Odile Poirel, Stéphane Jamain, Salah El Mestikawy, Stéphanie Daumas
The atypical vesicular glutamate transporter VGLUT3 is present in subpopulations of GABAergic interneurons in the cortex and the hippocampus, in subgroups of serotoninergic neurons in raphe nuclei, and in cholinergic interneurons in the striatum. C56BL/6N mice that no longer express VGLUT3 (VGLUT3-/- ) display anxiety-associated phenotype, increased spontaneous and cocaine-induced locomotor activity and decreased haloperidol-induced catalepsy. Inbred mouse strains differ markedly in their sensitivity to anxiety and behavioral responses elicited by drugs...
October 15, 2018: Genes, Brain, and Behavior
Atheir I Abbas, Marina J M Sundiang, Britt Henoch, Mitchell P Morton, Scott S Bolkan, Alan J Park, Alexander Z Harris, Christoph Kellendonk, Joshua A Gordon
Decreased hippocampal-prefrontal synchrony may mediate cognitive deficits in schizophrenia, but it remains unclear which cells orchestrate this long-range synchrony. Parvalbumin (PV)- and somatostatin (SOM)-expressing interneurons show histological abnormalities in individuals with schizophrenia and are hypothesized to regulate oscillatory synchrony within the prefrontal cortex. To examine the relationship between interneuron function, long-range hippocampal-prefrontal synchrony, and cognition, we optogenetically inhibited SOM and PV neurons in the medial prefrontal cortex (mPFC) of mice performing a spatial working memory task while simultaneously recording neural activity in the mPFC and the hippocampus (HPC)...
October 8, 2018: Neuron
Christina M Grimm, Sonat Aksamaz, Stefanie Schulz, Jasper Teutsch, Piotr Sicinski, Birgit Liss, Dennis Kätzel
Elevated activity at the output stage of the anterior hippocampus has been described as a physiological endophenotype of schizophrenia, and its development maps onto the transition from the prodromal to the psychotic state. Interventions that halt the spreading glutamatergic over-activity in this region and thereby the development of overt schizophrenia could be promising therapies. However, animal models with high construct validity to support such pre-clinical development are scarce. The Cyclin-D2 knockout (CD2-KO) mouse model shows a hippocampal parvalbumin-interneuron dysfunction, and its pattern of hippocampal over-activity shares similarities with that seen in prodromal patients...
October 9, 2018: Translational Psychiatry
Tabish Hussain, Hyunsuk Kil, Bharathi Hattiangady, Jaeho Lee, Maheedhar Kodali, Bing Shuai, Sahithi Attaluri, Yoko Takata, Jianjun Shen, Martin C Abba, Ashok K Shetty, C Marcelo Aldaz
The association of WW domain-containing oxidoreductase WWOX gene loss of function with central nervous system (CNS) related pathologies is well documented. These include spinocerebellar ataxia, epilepsy and mental retardation (SCAR12, OMIM: 614322) and early infantile epileptic encephalopathy (EIEE28, OMIM: 616211) syndromes. However, there is complete lack of understanding of the pathophysiological mechanisms at play. In this study, using a Wwox knockout (Wwox KO) mouse model (2 weeks old, both sexes) and stereological studies we observe that Wwox deletion leads to a significant reduction in the number of hippocampal GABA-ergic (γ-aminobutyric acid) interneurons...
October 2, 2018: Neurobiology of Disease
Vanessa Cattaud, Charlotte Bezzina, Christophe C Rey, Camille Lejards, Lionel Dahan, Laure Verret
Recent findings show that parvalbumin (PV) interneuron function is impaired in Alzheimer's disease (AD), and that this impairment in PV function can be linked to network dysfunction and memory deficits. PV cells are often associated with a specific extracellular matrix, the perineuronal net (PNN). PNNs are believed to protect PV cell integrity, and whether the amyloidopathy affects PNNs remains unclear. Here, we evaluated the number of PV cells with and without PNNs in the hippocampus of the Tg2576 mouse model of AD at different stages of the disease...
September 5, 2018: Neurobiology of Aging
Li Liu, Li Zhang, Tao Wang, Li Chen
The medial prefrontal cortex (mPFC) receives direct and indirect projections from the ventral hippocampus (VH) and plays an important role in the regulation of anxiety. However, the effect of the mPFC dopamine D1 receptor on anxiety-like behaviors induced by inhibition of glutamatergic activity in the VH has not been described. Here, we examined the effects of SKF38393, a selective dopamine D1 receptor agonist, on anxiety-like behaviors induced by NMDA receptor inhibition in the VH and neuron firing activity of mPFC...
September 20, 2018: Brain Research
Katrine Skovgård, Claus Agerskov, Kristi A Kohlmeier, Kjartan F Herrik
Cognitive impairments in Alzheimer's disease (AD) have been associated with alterations in neuronal oscillatory activity, of which hippocampal theta and gamma oscillations are essential for the coordination of neuronal networks during cognitive functions. Cognitive deterioration in AD is delayed by symptomatic treatment with donepezil and other acetylcholinesterase inhibitors (AChEIs). However, the efficacy of symptomatic monotherapy is insufficient. Combining 5-HT receptor antagonists with AChEIs represents a promising new approach for symptomatic treatment of AD...
September 19, 2018: Neuropharmacology
Ji-Eun Kim, Tae-Cheon Kang
Under pathophysiological conditions, aberrant mitochondrial dynamics lead to the different types of neuronal death: excessive mitochondrial fission provokes apoptosis and abnormal mitochondrial elongation induces necrosis. However, the underlying mechanisms how the different mitochondrial dynamics result in the distinct neuronal death patterns have been elusive. In the present study, status epilepticus (SE) evoked excessive mitochondrial fission in parvalbumin (PV) cells (one of GABAergic interneurons) and abnormal mitochondrial elongation in CA1 neurons in the rat hippocampus...
2018: Frontiers in Cellular Neuroscience
Alexandru Cǎlin, Mihai Stancu, Ana-Maria Zagrean, John G R Jefferys, Andrei S Ilie, Colin J Akerman
Current anti-epileptic medications that boost synaptic inhibition are effective in reducing several types of epileptic seizure activity. Nevertheless, these drugs can generate significant side-effects and even paradoxical responses due to the broad nature of their action. Recently developed chemogenetic techniques provide the opportunity to pharmacologically recruit endogenous inhibitory mechanisms in a selective and circuit-specific manner. Here, we use chemogenetics to assess the potential of suppressing epileptiform activity by enhancing the synaptic output from three major interneuron populations in the rodent hippocampus: parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP) expressing interneurons...
2018: Frontiers in Cellular Neuroscience
Alexandra P Chatzikalymniou, Frances K Skinner
Oscillations in local field potentials (LFPs) are prevalent and contribute to brain function. An understanding of the cellular correlates and pathways affecting LFPs is needed, but many overlapping pathways in vivo make this difficult to achieve. A prevalent LFP rhythm in the hippocampus associated with memory processing and spatial navigation is the θ (3-12 Hz) oscillation. θ rhythms emerge intrinsically in an in vitro whole hippocampus preparation and this reduced preparation makes it possible to assess the contribution of different cell types to LFP generation...
July 2018: ENeuro
Rosanna Migliore, Carmen A Lupascu, Luca L Bologna, Armando Romani, Jean-Denis Courcol, Stefano Antonel, Werner A H Van Geit, Alex M Thomson, Audrey Mercer, Sigrun Lange, Joanne Falck, Christian A Rössert, Ying Shi, Olivier Hagens, Maurizio Pezzoli, Tamas F Freund, Szabolcs Kali, Eilif B Muller, Felix Schürmann, Henry Markram, Michele Migliore
Every neuron is part of a network, exerting its function by transforming multiple spatiotemporal synaptic input patterns into a single spiking output. This function is specified by the particular shape and passive electrical properties of the neuronal membrane, and the composition and spatial distribution of ion channels across its processes. For a variety of physiological or pathological reasons, the intrinsic input/output function may change during a neuron's lifetime. This process results in high variability in the peak specific conductance of ion channels in individual neurons...
September 2018: PLoS Computational Biology
Frank Ativie, Joanna A Komorowska, Eva Beins, Önder Albayram, Till Zimmer, Andreas Zimmer, Dario Tejera, Michael Heneka, Andras Bilkei-Gorzo
Microglia, the resident immune cells of the brain, play important roles in defending the brain against pathogens and supporting neuronal circuit plasticity. Chronic or excessive pro-inflammatory responses of microglia damage neurons, therefore their activity is tightly regulated. Pharmacological and genetic studies revealed that cannabinoid type 1 (CB1) receptor activity influences microglial activity, although microglial CB1 receptor expression is very low and activity-dependent. The CB1 receptor is mainly expressed on neurons in the central nervous system (CNS)-with an especially high level on GABAergic interneurons...
2018: Frontiers in Molecular Neuroscience
Karri Lamsa, Petrina Lau
Formation of a cell assembly, a group of cortical neurons that function co-operatively to sustain an active memory trace, arises from changes in the connections between neurons. Establishment of memory traces is thought to rely on long-term plasticity in excitatory glutamatergic synapses interconnecting principal cells. In addition, recent studies in the hippocampus in vivo indicate that reconfiguration of GABAergic inhibitory interneuron activity also occurs during long-term memory encoding. Recent experiments in anesthetized, as well as in freely moving animals, demonstrate that learning-related hippocampal activities are associated with persistent changes in GABAergic interneuron firing rates and alterations in protein expression levels regulating GABA release...
September 5, 2018: Current Opinion in Neurobiology
Sanja Mikulovic, Carlos Ernesto Restrepo, Samer Siwani, Pavol Bauer, Stefano Pupe, Adriano B L Tort, Klas Kullander, Richardson N Leão
Dorsal and ventral hippocampus regions exert cognition and emotion-related functions, respectively. Since both regions display rhythmic activity, specific neural oscillatory pacemakers may underlie their functional dichotomy. Type 1 theta oscillations are independent of cholinergic transmission and are observed in the dorsal hippocampus during movement and exploration. In contrast, type 2 theta depends on acetylcholine and appears when animals are exposed to emotionally laden contexts such as a predator presence...
September 7, 2018: Nature Communications
Linda K Friedman, Joann P Wongvravit
Anticonvulsant effects of cannabidiol (CBD), a nonpsychoactive cannabinoid, have not been investigated in the juvenile brain. We hypothesized that CBD would attenuate epileptiform activity at an age when the brain first becomes vulnerable to neurotoxicity and social/cognitive impairments. To induce seizures, kainic acid (KA) was injected either into the hippocampus (KAih) or systemically (KAip) on postnatal (P) day 20. CBD was coadministered (KA + CBDih, KA + CBDip) or injected 30 minutes postseizure onset (KA/CBDih, KA/CBDip)...
October 1, 2018: Journal of Neuropathology and Experimental Neurology
Shuai Cui, Kun Wang, Sheng-Bing Wu, Guo-Qi Zhu, Jian Cao, Yi-Ping Zhou, Mei-Qi Zhou
The hippocampus is involved in the regulation of the autonomic nervous system, together with the hypothalamus and brainstem nuclei, such as the paraventricular nucleus and nucleus tractus solitarius. The vagus nerve-nucleus tractus solitarius pathway has an important role in cardiovascular reflex regulation. Myocardial ischemia has been shown to cause changes in the autonomic nervous system, affecting the dynamic equilibrium of the sympathetic and vagal nerves. However, it remains poorly understood how the hippocampus communicates with brainstem nuclei to regulate the autonomic nervous system and alleviate myocardial ischemic tissue damage...
September 2018: Neural Regeneration Research
Xin Wu, Ramkumar Kuruba, Doodipala Samba Reddy
Organophosphates (OP) such as the pesticide diisopropylfluorophosphate (DFP) and the nerve agent sarin are lethal chemicals that induce seizures, status epilepticus (SE), and brain damage. Midazolam, a benzodiazepine modulator of synaptic GABA-A receptors, is currently considered as a new anticonvulsant for nerve agents. Here, we characterized the time-course of protective efficacy of midazolam (0.2-5 mg/kg, i.m.) in rats exposed to DFP, a chemical threat agent and surrogate for nerve agents. Behavioral and EEG seizures were monitored for 24 h after DFP exposure...
August 16, 2018: Journal of Pharmacology and Experimental Therapeutics
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