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hilar mossy cells

Yanjun Sun, Steven F Grieco, Todd C Holmes, Xiangmin Xu
Hilar mossy cells are the prominent glutamatergic cell type in the dentate hilus of the dentate gyrus (DG); they have been proposed to have critical roles in the DG network. To better understand how mossy cells contribute to DG function, we have applied new viral genetic and functional circuit mapping approaches to quantitatively map and compare local and long-range circuit connections of mossy cells and dentate granule cells in the mouse. The great majority of inputs to mossy cells consist of two parallel inputs from within the DG: an excitatory input pathway from dentate granule cells and an inhibitory input pathway from local DG inhibitory neurons...
March 2017: ENeuro
Kun Zhu, Bo Yuan, Ming Hu, Gai-Feng Feng, Yong Liu, Jian-Xin Liu
Epileptic seizures lead to aberrant hippocampal neurogenesis, including increased proliferation of neural progenitors and abnormal integrations of newly generated granule cells - hilar ectopic granule cells (EGCs), mossy fiber sprouting (MFS), and hilar basal dendrites (HBDs). Previous results from ablating hippocampal neurogenesis after acute seizures have been controversial with regards to the development of spontaneous recurrent seizures (SRSs). While ablation of hippocampal newborn cells was effective, a sufficient decrease of subsequent abnormal integrations in chronically epileptic hippocampus was not well-established in these studies...
April 11, 2017: Epilepsy Research
Paul S Buckmaster, Emily Abrams, Xiling Wen
Epilepsy occurs in one of 26 people. Temporal lobe epilepsy is common and can be difficult to treat effectively. It can develop after brain injuries that damage the hippocampus. Multiple pathophysiological mechanisms involving the hippocampal dentate gyrus have been proposed. This study evaluated a mouse model of temporal lobe epilepsy to test which pathological changes in the dentate gyrus correlate with seizure frequency and help prioritize potential mechanisms for further study. FVB mice (nā€‰=ā€‰127) that had experienced status epilepticus after systemic treatment with pilocarpine 31-61 days earlier were video-monitored for spontaneous, convulsive seizures 9 hr/day every day for 24-36 days...
August 1, 2017: Journal of Comparative Neurology
Sanoara Mazid, Baila S Hall, Shannon C Odell, Khalifa Stafford, Andreina D Dyer, Tracey A Van Kempen, Jane Selegean, Bruce S McEwen, Elizabeth M Waters, Teresa A Milner
Drug addiction requires associative learning processes that critically involve hippocampal circuits, including the opioid system. We recently found that acute and chronic stress, important regulators of addictive processes, affect hippocampal opioid levels and mu opioid receptor trafficking in a sexually dimorphic manner. Here, we examined whether acute and chronic stress similarly alters the levels and trafficking of hippocampal delta opioid receptors (DORs). Immediately after acute immobilization stress (AIS) or one-day after chronic immobilization stress (CIS), the brains of adult female and male rats were perfusion-fixed with aldehydes...
December 2016: Neurobiology of Stress
Aynara C Wulsin, James P Herman, Steve C Danzer
Status epilepticus (SE) induces rapid hyper-activation of the hypothalamo-pituitary-adrenocortical (HPA) axis. HPA axis hyperactivity results in excess exposure to high levels of circulating glucocorticoids, which are associated with neurotoxicity and depression-like behavior. These observations have led to the hypothesis that HPA axis dysfunction may exacerbate SE-induced brain injury. To test this hypothesis, we used the mouse pilocarpine model of epilepsy to determine whether use of the glucocorticoid receptor antagonist RU486 can attenuate hippocampal pathology following SE...
2016: Frontiers in Neurology
Jian-Xin Liu, Ming Hu, Kun Zhu, Xin-Lin Chen, Jian-Shui Zhang, Bo Yuan, Yong Liu
Abnormal hippocampal neurogenesis after acute seizures has been well addressed. However, whether newly generated cells continued to be disturbed even they were born in the chronic stage after pilocarpine-induce status epilepticus has remained elusive. Labeling dividing progenitors and their progeny with retroviral vector expressing green fluorescent protein or proliferation marker 5-bromo-2'-deoxyuridine at 3 months post pilocarpine-induced status epilepticus in mice, a spot of newly born neurons exhibiting hilar ectopic location (4...
August 18, 2016: Epilepsy Research
Scott W Harden, Charles J Frazier
Delivery of exogenous oxytocin (OXT) to central oxytocin receptors (OXT-Rs) is currently being investigated as a potential treatment for conditions such as post-traumatic stress disorder (PTSD), depression, social anxiety, and autism spectrum disorder (ASD). Despite significant research implicating central OXT signaling in modulation of mood, affect, social behavior, and stress response, relatively little is known about the cellular and synaptic mechanisms underlying these complex actions, particularly in brain regions which express the OXT-R but lie outside of the hypothalamus (where OXT-synthesizing neurons reside)...
September 2016: Hippocampus
Xiaoping Du, Matthew B West, Weihua Cheng, Donald L Ewert, Wei Li, Debra Saunders, Rheal A Towner, Robert A Floyd, Richard D Kopke
Traumatic brain injury (TBI) can lead to early onset dementia and other related neurodegenerative diseases. We previously demonstrated that damage to the central auditory pathway resulting from blast-induced TBI (bTBI) could be significantly attenuated by a combinatorial antioxidant treatment regimen. In the current study, we examined the localization patterns of normal Tau and the potential blast-induced accumulation of neurotoxic variants of this microtubule-associated protein that are believed to potentiate the neurodegenerative effects associated with synaptic dysfunction in the hippocampus following three successive blast overpressure exposures in nontransgenic rats...
2016: Oxidative Medicine and Cellular Longevity
A L Althaus, H Zhang, J M Parent
Dentate granule cell (DGC) mossy fiber sprouting (MFS) in mesial temporal lobe epilepsy (mTLE) is thought to underlie the creation of aberrant circuitry which promotes the generation or spread of spontaneous seizure activity. Understanding the extent to which populations of DGCs participate in this circuitry could help determine how it develops and potentially identify therapeutic targets for regulating aberrant network activity. In this study, we investigated how DGC birthdate influences participation in MFS and other aspects of axonal plasticity using the rat pilocarpine-induced status epilepticus (SE) model of mTLE...
February 2016: Neurobiology of Disease
Vassilis Cutsuridis, Panayiota Poirazi
A recent experimental study (Mizuseki, Sirota, Pastalkova, & Buzsaki, 2009) has shown that the temporal delays between population activities in successive entorhinal and hippocampal anatomical stages are longer (about 70-80ms) than expected from axon conduction velocities and passive synaptic integration of feed-forward excitatory inputs. We investigate via computer simulations the mechanisms that give rise to such long temporal delays in the hippocampus structures. A model of the dentate gyrus (DG), CA3 and CA1 microcircuits is presented that uses biophysical representations of the major cell types including granule cells, CA3 and CA1 pyramidal cells (PCs) and six types of interneurons: basket cells (BCs), axo-axonic cells (AACs), bistratified cells (BSCs), oriens lacunosum-moleculare cells (OLMs), mossy cells (MCs) and hilar perforant path associated cells (HC)...
April 2015: Neurobiology of Learning and Memory
Yefeng Yuan, Hao Wang, Zongbo Wei, Wei Li
Schizophrenia (SCZ) is a complex disease that has been regarded as a neurodevelopmental, synaptic or epigenetic disorder. Here we provide evidence that neurodegeneration is implicated in SCZ. The DTNBP1 (dystrobrevin-binding protein 1) gene encodes dysbindin-1 and is a leading susceptibility gene of SCZ. We previously reported that the dysbindin-1C isoform regulates the survival of the hilar glutamatergic mossy cells in the dentate gyrus, which controls the adult hippocampal neurogenesis. However, the underlying mechanism of hilar mossy cell loss in the dysbindin-1-deficient sandy (sdy) mice (a mouse model of SCZ) is unknown...
January 20, 2015: Journal of Genetics and Genomics, Yi Chuan Xue Bao
Emma Puighermanal, Anne Biever, Julie Espallergues, Giuseppe Gangarossa, Dimitri De Bundel, Emmanuel Valjent
Increasing evidences suggest that dopamine facilitates the encoding of novel memories by the hippocampus. However, the role of dopamine D2 receptors (D2R) in such regulations remains elusive due to the lack of the precise identification of hippocampal D2R-expressing cells. To address this issue, mice expressing the ribosomal protein Rpl22 tagged with the hemagglutinin (HA) epitope were crossed with Drd2-Cre mice allowing the selective expression of HA in D2R-containing cells (Drd2-Cre:RiboTag mice). This new transgenic model revealed a more widespread pattern of D2R-expressing cells identified by HA immunoreactivity than the one initially reported in Drd2-EGFP mice, in which the hilar mossy cells were the main neuronal population detectable...
July 2015: Hippocampus
Wei Zhang, Ajoy K Thamattoor, Christopher LeRoy, Paul S Buckmaster
Numerous hypotheses of temporal lobe epileptogenesis have been proposed, and several involve hippocampal mossy cells. Building on previous hypotheses we sought to test the possibility that after epileptogenic injuries surviving mossy cells develop into super-connected seizure-generating hub cells. If so, they might require more cellular machinery and consequently have larger somata, elongate their dendrites to receive more synaptic input, and display higher frequencies of miniature excitatory synaptic currents (mEPSCs)...
May 2015: Hippocampus
Hao Wang, Yefeng Yuan, Zhao Zhang, Hui Yan, Yaqin Feng, Wei Li
DTNBP1 (dystrobrevin-binding protein 1), which encodes dysbindin-1, is one of the leading susceptibility genes for schizophrenia. Both dysbindin-1B and -1C isoforms are decreased, but the dysbindin-1A isoform is unchanged in schizophrenic hippocampal formation, suggesting dysbindin-1 isoforms may have distinct roles in schizophrenia. We found that mouse dysbindin-1C, but not dysbindin-1A, is localized in the hilar glutamatergic mossy cells of the dentate gyrus. The maturation rate of newborn neurons in sandy (sdy) mice, in which both dysbindin-1A and -1C are deleted, is significantly delayed when compared with that in wild-type mice or with that in muted (mu) mice in which dysbindin-1A is destabilized but dysbindin-1C is unaltered...
October 17, 2014: Journal of Biological Chemistry
Brandon J Wright, Meyer B Jackson
The dentate gyrus serves as a gateway to the hippocampus, filtering and processing sensory inputs as an animal explores its environment. The hilus occupies a strategic position within the dentate gyrus from which it can play a pivotal role in these functions. Inputs from dentate granule cells converge on the hilus, and excitatory hilar mossy cells redistribute these signals back to granule cells to transform a pattern of cortical input into a new pattern of output to the hippocampal CA3 region. Using voltage-sensitive dye to image electrical activity in rat hippocampal slices, we explored how long-term potentiation (LTP) of different excitatory synapses modifies the flow of information...
July 16, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Lyndsey L Anderson, Christopher H Thompson, Nicole A Hawkins, Ravi D Nath, Adam A Petersohn, Sridharan Rajamani, William S Bush, Wayne N Frankel, Carlos G Vanoye, Jennifer A Kearney, Alfred L George
OBJECTIVE: Evidence from basic neurophysiology and molecular genetics has implicated persistent sodium current conducted by voltage-gated sodium (NaV ) channels as a contributor to the pathogenesis of epilepsy. Many antiepileptic drugs target NaV channels and modulate neuronal excitability, mainly by a use-dependent block of transient sodium current, although suppression of persistent current may also contribute to the efficacy of these drugs. We hypothesized that a drug or compound capable of preferential inhibition of persistent sodium current would have antiepileptic activity...
August 2014: Epilepsia
Sami Boudkkazi, Aline Brechet, Jochen Schwenk, Bernd Fakler
Cornichon2 (CNIH2), an integral component of AMPA receptor (AMPAR) complexes in the mammalian brain, slows deactivation and desensitization of heterologously reconstituted receptor channels. Its significance in neuronal signal transduction, however, has remained elusive. Here we show by paired recordings that CNIH2-containing AMPARs dictate the slow decay of excitatory postsynaptic currents (EPSCs) elicited in hilar mossy cells of the hippocampus by single action potentials in mossy fiber boutons (MFB). Selective knockdown of CNIH2 markedly accelerated EPSCs in individual MFB-mossy cell synapses without altering the EPSC amplitude...
May 21, 2014: Neuron
W Bradley Rittase, Yu Dong, DaRel Barksdale, Zygmunt Galdzicki, Suzanne B Bausch
Emerging evidence suggests that neuronal responses to N-methyl-d-aspartate (NMDAR) activation/inactivation are influenced by subunit composition. For example, activation of synaptic NMDAR (comprised of GluN2A>GluN2B) phosphorylates cAMP-response-element-binding protein (CREB) at Ser 133, induces BDNF expression and promotes neuronal survival. Activation of extrasynaptic NMDAR (comprised of GluN2B>GluN2) dephosphorylates CREB (Ser 133), reduces BDNF expression and triggers neuronal death. These results led us to hypothesize that chronic inhibition of GluN2B-containing NMDAR would increase CREB (Ser 133) phosphorylation, increase BDNF levels and subsequently alter downstream dynorphin (DYN) and neuropeptide Y (NPY) expression...
May 2014: Molecular and Cellular Neurosciences
Guillaume Etter, Wojciech Krezel
Hippocampal control of memory formation is regulated by dopaminergic signaling. Whereas the role of dopamine D1 receptors is well documented in such regulations, functions of dopamine D2 receptors (DRD2) are not fully understood. Using fluorescence in situ hybridization we demonstrate that Drd2 expression in the hippocampus of wild-type mice is limited to glutamatergic hilar mossy cells. Using whole cell electrophysiological recordings in hippocampal slice preparations, we provide evidence that unlike in basal ganglia, activation of DRD2 by the selective agonist, quinpirole, induces a long-lasting increase in excitability of hilar mossy cells, which can be blocked by the DRD2 antagonist raclopride...
July 2014: Hippocampus
Ross W Anderson, Ben W Strowbridge
The hippocampal formation receives strong cholinergic input from the septal/diagonal band complex. Although the functional effects of cholinergic activation have been extensively studied in pyramidal neurons within the hippocampus and entorhinal cortex, less is known about the role of cholinergic receptors on dentate gyrus neurons. Using intracellular recordings from rat dentate hilar neurons, we find that activation of m1-type muscarinic receptors selectively increases the excitability of glutamatergic mossy cells but not of hilar interneurons...
April 15, 2014: Learning & Memory
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