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Tessa E Fuhrer, Thulani H Palpagama, Henry J Waldvogel, Beth J L Synek, Clinton Turner, Richard L Faull, Andrea Kwakowsky
Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain and plays an important role in regulating neuronal excitability. GABA reuptake from the synapse is dependent on specific transporters - mainly GAT-1, GAT-3 and BGT-1 (GATs). This study is the first to show alterations in the expression of the GATs in the Alzheimer's disease (AD) hippocampus, entorhinal cortex and superior temporal gyrus. We found a significant increase in BGT-1 expression associated with AD in all layers of the dentate gyrus, in the stratum oriens of the CA2 and CA3 and the superior temporal gyrus...
April 4, 2017: Neuroscience
Bai Hui Chen, Ji Hyeon Ahn, Joon Ha Park, Bich Na Shin, Yun Lyul Lee, Il Jun Kang, Seongkweon Hong, Yang Hee Kim, Yong Hwan Jeon, In Hye Kim, Jeong Hwi Cho, Tae-Kyeong Lee, Jae Chul Lee, Moo-Ho Won, Jun Hwi Cho, Joong Bum Moon
Glycogen synthase kinase 3β (GSK-3β) is a key downstream protein in the PI3K/Akt pathway. Phosphorylation of serine 9 of GSK-3β (GSK-3β activity inhibition) promotes cell survival. In this study, we examined changes in expressions of GSK-3β and phosphorylation of GSK-3β (p-GSK-3β) in the gerbil hippocampal CA1 area after 5 min of transient cerebral ischemia. GSK-3β immunoreactivity in the CA1 area was increased in pyramidal cells at 6 h after ischemia-reperfusion. It was decreased in CA1 pyramidal cells from 12 h after ischemia-reperfusion, and hardly detected in the CA1 pyramidal cells at 5 days after ischemia-reperfusion...
March 28, 2017: Neurochemical Research
Vladislav Sekulić, Frances K Skinner
Although biophysical details of inhibitory neurons are becoming known, it is challenging to map these details onto function. Oriens-lacunosum/moleculare (O-LM) cells are inhibitory cells in the hippocampus that gate information flow, firing while phase-locked to theta rhythms. We build on our existing computational model database of O-LM cells to link model with function. We place our models in high-conductance states and modulate inhibitory inputs at a wide range of frequencies. We find preferred spiking recruitment of models at high (4-9 Hz) or low (2-5 Hz) theta depending on, respectively, the presence or absence of h-channels on their dendrites...
March 20, 2017: ELife
Linda Suzanne David, Lisa Topolnik
Status epilepticus (SE) is associated with complex reorganization of hippocampal circuits involving a significant loss of specific subtypes of GABAergic interneurons. While adaptive circuit plasticity may increase the chances for recruitment of surviving interneurons, the underlying mechanisms remain largely unknown. We studied the alterations in the inhibitory tone received by the hippocampal CA1 oriens/alveus (O/A) interneurons from the vasoactive intestinal peptide (VIP)- and calretinin (CR)-expressing interneurons using the pilocarpine-induced status epilepticus (SE) model of epilepsy...
March 15, 2017: Experimental Neurology
Elizabeth Nicholson, Dimitri M Kullmann
KEY POINTS: Regular-spiking interneurons in the hippocampal stratum oriens exhibit a form of long-term potentiation of excitatory transmission that is independent of NMDA receptors but requires co-activation of Ca(2+) -permeable AMPA receptors and group I metabotropic glutamate receptors. We show that T-type Ca(2+) channels are present in such interneurons. Blockade of T-type currents prevents the induction of long-term potentiation, and also interferes with long-lasting potentiation induced either by postsynaptic trains of action potentials or by pairing postsynaptic hyperpolarization with activation of group I metabotropic receptors...
January 30, 2017: Journal of Physiology
Yectivani Juárez-Muñoz, Alejandro Rivera-Olvera, Laura E Ramos-Languren, Martha L Escobar
CaMKII has been proposed as a molecular substrate for long-term memory storage due to its capacity to maintain an active autophosporylated state even after the decay of the external stimuli. The hippocampal mossy fiber-CA3 pathway (MF-CA3) is considered as a relevant area for acquisition and storage of different learning tasks. MF-CA3 pathway exhibits a form of LTP characterized by a slow initial increase in the EPSP slope that is independent of NMDA receptors activation. Our previous studies show that application of high frequency stimulation sufficient to elicit MF-CA3 LTP produces structural reorganization, in a manner independent of LTP induction, at the stratum oriens of hippocampal CA3 area 7days after stimulation...
December 27, 2016: Neurobiology of Learning and Memory
Sivan Subburaju, Andrew J Coleman, Miles G Cunningham, W Brad Ruzicka, Francine M Benes
GABAergic dysfunction in hippocampus, a key feature of schizophrenia (SZ), may contribute to cognitive impairment in this disorder. In stratum oriens (SO) of sector CA3/2 of the human hippocampus, a network of genes involved in the regulation of glutamic acid decarboxylase GAD67 has been identified. Several of the genes in this network including epigenetic factors histone deacetylase 1 (HDAC1) and death-associated protein 6 (DAXX), the GABAergic enzyme GAD65 as well as the kainate receptor (KAR) subunits GluR6 and 7 show significant changes in expression in this area in SZ...
October 12, 2016: Cerebral Cortex
Jun Yamada, Shozo Jinno
Subsets of GABAergic neurons are surrounded by perineuronal nets (PNNs), which play a critical role in the regulation of neural plasticity and neuroprotection. Although the plant lectin Wisteria floribunda agglutinin (WFA) has been commonly used to label PNNs, WFA only detects N-acetyl-d-galactosamine on aggrecan, a member of the lectican family. In this study, we used WFA and the antibody against the core protein of aggrecan (ACAN) to investigate the molecular heterogeneity of aggrecan-based PNNs around five subclasses of parvalbumin-expressing (PV+) γ-aminobutyric acid (GABA)ergic neurons in the CA1 and CA3 regions of the mouse hippocampus...
April 1, 2017: Journal of Comparative Neurology
Elise Kleeman, Sakura Nakauchi, Hailing Su, Richard Dang, Marcelo A Wood, Katumi Sumikawa
Children of mothers who smoked during pregnancy are at significantly greater risk for cognitive impairments including memory deficits, but the mechanisms underlying this effect remain to be understood. In rodent models of smoking during pregnancy, early postnatal nicotine exposure results in impaired long-term hippocampus-dependent memory, functional loss of α2-containing nicotinic acetylcholine receptors (α2(∗) nAChRs) in oriens-lacunosum moleculare (OLM) cells, increased CA1 network excitation, and unexpected facilitation of long-term potentiation (LTP) at Schaffer collateral-CA1 synapses...
December 2016: Neurobiology of Learning and Memory
Chelsea M Griffith, Mi-Xin Xie, Wen-Ying Qiu, Andrew A Sharp, Chao Ma, Aihua Pan, Xiao-Xin Yan, Peter R Patrylo
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by beta-amyloid (Aβ) deposition, neurofibrillary tangles and cognitive decline. Recent pharmacologic studies have found that ATP-sensitive potassium (KATP) channels may play a role in AD and could be a potential therapeutic target. Interestingly, these channels are found in both neurons and astrocytes. One of the hallmarks associated with AD is reactive gliosis and a change in astrocytic function has been identified in several neuropathological conditions including AD...
November 12, 2016: Neuroscience
Yu-Yin Huang, Yu-Chao Liu, Cheng-Ta Lee, Yen-Chu Lin, Mong-Lien Wang, Yi-Ping Yang, Kaung-Yi Chang, Shih-Hwa Chiou
Lamotrigine (LTG) is generally considered as a voltage-gated sodium (Nav) channel blocker. However, recent studies suggest that LTG can also serve as a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel enhancer and can increase the excitability of GABAergic interneurons (INs). Perisomatic inhibitory INs, predominantly fast-spiking basket cells (BCs), powerfully inhibit granule cells (GCs) in the hippocampal dentate gyrus. Notably, BCs express abundant Nav channels and HCN channels, both of which are able to support sustained action potential generation...
July 22, 2016: International Journal of Molecular Sciences
Jian-Xin Liu, Xia Cao, Yong Liu, Feng-Ru Tang
Chemokine and receptor systems play important roles in different animal models of status epileptics and epileptogenesis. Here, we identified protein and gene expression of chemokine receptor 6 in the hippocampus of Swiss mice with immunohistochemistry and RT-PCR respectively. Immunohistochemical study showed that CCR6 immunopositive product was localized in different subtypes of hippocampal interneurons, in apical dendrites of pyramidal neurons of CA1 area and other laminas of the hippocampus. Strongly stained CCR6 immunopositive product was found in calbindin, calretinin, parvalbumin immunopositive interneurons in the stratum oriens of CA1 area...
October 2016: Epilepsy Research
Michael Willis, Maria Trieb, Irmgard Leitner, Georg Wietzorrek, Josef Marksteiner, Hans-Günther Knaus
SK2 (KCa2.2) channels are voltage-independent Ca(2+)-activated K(+) channels that regulate neuronal excitability in brain regions important for memory formation. In this study, we investigated the distribution and expression of SK2 channels in human brain by Western blot analysis and immunohistochemistry. Immunoblot analysis of human brain indicated expression of four distinct SK2 channel isoforms: the standard, the long and two short isoforms. Immunohistochemistry in paraffin-embedded post-mortem brain sections was performed in the hippocampal formation, amygdala and neocortex...
March 2017: Brain Structure & Function
Carey Y L Huh, Bénédicte Amilhon, Katie A Ferguson, Frédéric Manseau, Susana G Torres-Platas, John P Peach, Stephanie Scodras, Naguib Mechawar, Frances K Skinner, Sylvain Williams
UNLABELLED: Theta oscillations are essential for learning and memory, and their generation requires GABAergic interneurons. To better understand how theta is generated, we explored how parvalbumin (PV) and somatostatin (SOM) interneurons in CA1 stratum oriens/alveus fire during hippocampal theta and investigated synaptic mechanisms underlying their behavior. Combining the use of transgenic mice to visually identify PV and SOM interneurons and the intact hippocampal preparation that can generate theta oscillations in vitro without cholinergic agonists, we performed simultaneous field and whole-cell recordings...
June 22, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Morgan Mosley, Charisma Shah, Kiriana A Morse, Stephen A Miloro, Melissa M Holmes, Todd H Ahern, Nancy G Forger
The importance of cell death in brain development has long been appreciated, but many basic questions remain, such as what initiates or terminates the cell death period. One obstacle has been the lack of quantitative data defining exactly when cell death occurs. We recently created a "cell death atlas," using the detection of activated caspase-3 (AC3) to quantify apoptosis in the postnatal mouse ventral forebrain and hypothalamus, and found that the highest rates of cell death were seen at the earliest postnatal ages in most regions...
January 1, 2017: Journal of Comparative Neurology
Jonathan Bertram, Leif Koschützke, Jörg P Pfannmöller, Jennifer Esche, Laura van Diepen, Andreas W Kuss, Bianca Hartmann, Dusan Bartsch, Martin Lotze, Oliver von Bohlen Und Halbach
SrGAP3 belongs to the family of Rho GTPase proteins. These proteins are thought to play essential roles in development and in the plasticity of the nervous system. SrGAP3-deficient mice have recently been created and approximately 10 % of these mice developed a hydrocephalus and died shortly after birth. The others survived into adulthood, but displayed neuroanatomical alteration, including increased ventricular size. We now show that SrGAP3-deficient mice display increased brain weight together with increased hippocampal volume...
October 2016: Cell and Tissue Research
William D Marks, Jason J Paris, Christina J Schier, Melissa D Denton, Sylvia Fitting, A Rory McQuiston, Pamela E Knapp, Kurt F Hauser
Memory deficits are characteristic of HIV-associated neurocognitive disorders (HAND) and co-occur with hippocampal pathology. The HIV-1 transactivator of transcription (Tat), a regulatory protein, plays a significant role in these events, but the cellular mechanisms involved are poorly understood. Within the hippocampus, diverse populations of interneurons form complex networks; even subtle disruptions can drastically alter synaptic output, resulting in behavioral dysfunction. We hypothesized that HIV-1 Tat would impair cognitive behavior and injure specific hippocampal interneuron subtypes...
December 2016: Journal of Neurovirology
Thomas K Fung, Clayton S Law, L Stan Leung
Spike timing-dependent plasticity in the hippocampus has rarely been studied in vivo. Using extracellular potential and current source density analysis in urethane-anesthetized adult rats, we studied synaptic plasticity at the basal dendritic excitatory synapse in CA1 after excitation-spike (ES) pairing; E was a weak basal dendritic excitation evoked by stratum oriens stimulation, and S was a population spike evoked by stratum radiatum apical dendritic excitation. We hypothesize that positive ES pairing-generating synaptic excitation before a spike-results in long-term potentiation (LTP) while negative ES pairing results in long-term depression (LTD)...
June 1, 2016: Journal of Neurophysiology
Svetlana M Molchanova, Johanna Huupponen, Sari E Lauri, Tomi Taira
Direct electrical coupling between neurons through gap junctions is prominent during development, when synaptic connectivity is scarce, providing the additional intercellular connectivity. However, functional studies of gap junctions are hampered by the unspecificity of pharmacological tools available. Here we have investigated gap-junctional coupling between CA3 pyramidal cells in neonatal hippocampus and its contribution to early network activity. Four different gap junction inhibitors, including the general blocker carbenoxolone, decreased the frequency of network activity bursts in CA3 area of hippocampus of P3-6 rats, suggesting the involvement of electrical connections in the generation of spontaneous network activity...
August 2016: Neuropharmacology
S Subburaju, A J Coleman, W B Ruzicka, F M Benes
Schizophrenia (SZ) is associated with GABA neuron dysfunction in the hippocampus, particularly the stratum oriens of sector CA3/2. A gene expression profile analysis of human postmortem hippocampal tissue followed by a network association analysis had shown a number of genes differentially regulated in SZ, including the epigenetic factors HDAC1 and DAXX. To characterize the contribution of these factors to the developmental perturbation hypothesized to underlie SZ, lentiviral vectors carrying short hairpin RNA interference (shRNAi) for HDAC1 and DAXX were used...
January 26, 2016: Translational Psychiatry
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