scholarly journals Synaptic Plasticity and Excitation-Inhibition Balance in the Dentate Gyrus: Insights fromIn VivoRecordings in Neuroligin-1, Neuroligin-2, and Collybistin Knockouts

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Peter Jedlicka ◽  
Julia Muellerleile ◽  
Stephan W. Schwarzacher
Keyword(s):  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Granule Cell ◽  
Molecular Mechanisms ◽  
Granule Cells ◽  
Functional Characterization ◽  
Inhibitory Synapses ◽  
Spatial Learning And Memory ◽  
Dentate Granule Cell

The hippocampal dentate gyrus plays a role in spatial learning and memory and is thought to encode differences between similar environments. The integrity of excitatory and inhibitory transmission and a fine balance between them is essential for efficient processing of information. Therefore, identification and functional characterization of crucial molecular players at excitatory and inhibitory inputs is critical for understanding the dentate gyrus function. In this minireview, we discuss recent studies unraveling molecular mechanisms of excitatory/inhibitory synaptic transmission, long-term synaptic plasticity, and dentate granule cell excitability in the hippocampus of live animals. We focus on the role of three major postsynaptic proteins localized at excitatory (neuroligin-1) and inhibitory synapses (neuroligin-2 and collybistin).In vivorecordings of field potentials have the advantage of characterizing the effects of the loss of these proteins on the input-output function of granule cells embedded in a network with intact connectivity. The lack of neuroligin-1 leads to deficient synaptic plasticity and reduced excitation but normal granule cell output, suggesting unaltered excitation-inhibition ratio. In contrast, the lack of neuroligin-2 and collybistin reduces inhibition resulting in a shift towards excitation of the dentate circuitry.

The chemokine SDF1 regulates migration of dentate granule cells

Development ◽  
2002 ◽  
Vol 129 (18) ◽  
pp. 4249-4260 ◽  
Author(s):  
Anil Bagri ◽  
Theresa Gurney ◽  
Xiaoping He ◽  
Yong-Rui Zou ◽  
Dan R. Littman ◽  
...  
Keyword(s):  
Cell Migration ◽  
Dentate Gyrus ◽  
Granule Cell ◽  
Granule Cells ◽  
Ectopic Expression ◽  
Dentate Granule Cell ◽  
Vitro Assay ◽  
Dentate Granule Cells ◽  
Cell Position

The dentate gyrus is the primary afferent pathway into the hippocampus, but there is little information concerning the molecular influences that govern its formation. In particular, the control of migration and cell positioning of dentate granule cells is not clear. We have characterized more fully the timing and route of granule cell migration during embryogenesis using in utero retroviral injections. Using this information, we developed an in vitro assay that faithfully recapitulates important events in dentate gyrus morphogenesis. In searching for candidate ligands that may regulate dentate granule cell migration, we found that SDF1, a chemokine that regulates cerebellar and leukocyte migration, and its receptor CXCR4 are expressed in patterns that suggest a role in dentate granule cell migration. Furthermore, CXCR4 mutant mice have a defect in granule cell position. Ectopic expression of SDF1 in our explant assay showed that it directly regulates dentate granule cell migration. Our study shows that a chemokine is necessary for the normal development of the dentate gyrus, a forebrain structure crucial for learning and memory.

scholarly journals Enhanced LTP of population spikes in the dentate gyrus of mice haploinsufficient for neurobeachin

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Julia Muellerleile ◽  
Aline Blistein ◽  
Astrid Rohlmann ◽  
Frederieke Scheiwe ◽  
Markus Missler ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Granule Cell ◽  
Field Potential ◽  
Synaptic Function ◽  
Spatial Learning And Memory ◽  
Neurotransmitter Receptor ◽  
Cell Excitability ◽  
Neuronal Protein ◽  
Electrophysiological Recordings

Abstract Deletion of the autism candidate molecule neurobeachin (Nbea), a large PH-BEACH-domain containing neuronal protein, has been shown to affect synaptic function by interfering with neurotransmitter receptor targeting and dendritic spine formation. Previous analysis of mice lacking one allele of the Nbea gene identified impaired spatial learning and memory in addition to altered autism-related behaviours. However, no functional data from living heterozygous Nbea mice (Nbea+/−) are available to corroborate the behavioural phenotype. Here, we explored the consequences of Nbea haploinsufficiency on excitation/inhibition balance and synaptic plasticity in the intact hippocampal dentate gyrus of Nbea+/− animals in vivo by electrophysiological recordings. Based on field potential recordings, we show that Nbea+/− mice display enhanced LTP of the granule cell population spike, but no differences in basal synaptic transmission, synapse numbers, short-term plasticity, or network inhibition. These data indicate that Nbea haploinsufficiency causes remarkably specific alterations to granule cell excitability in vivo, which may contribute to the behavioural abnormalities in Nbea+/− mice and to related symptoms in patients.

Lack of β-amyloid cleaving enzyme-1 (BACE1) impairs long-term synaptic plasticity but enhances granule cell excitability and oscillatory activity in the dentate gyrus in vivo

2019 ◽  
Vol 224 (3) ◽  
pp. 1279-1290 ◽  
Author(s):  
Matej Vnencak ◽  
Marieke L. Schölvinck ◽  
Stephan W. Schwarzacher ◽  
Thomas Deller ◽  
Michael Willem ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Granule Cell ◽  
Oscillatory Activity ◽  
Cell Excitability ◽  
Β Amyloid

scholarly journals Adult-born granule cells support pathological microcircuits in the chronically epileptic dentate gyrus

2020 ◽  
Author(s):  
FT Sparks ◽  
Z Liao ◽  
W Li ◽  
I Soltesz ◽  
A Losonczy
Keyword(s):  
Dentate Gyrus ◽  
Local Field ◽  
Granule Cell ◽  
Topic Modeling ◽  
Granule Cells ◽  
Field Potential ◽  
Epileptiform Discharges ◽  
Interictal Epileptiform Discharges ◽  
Activity Dynamics

AbstractTemporal lobe epilepsy (TLE) is characterized by recurrent seizures driven by synchronous neuronal activity. The dentate gyrus (DG) region of the hippocampal formation is highly reorganized in chronic TLE; in particular, pathological remodeling of the “dentate gate” is thought to open up pathological conduction pathways for synchronous discharges and seizures in the mesial temporal lobe. However, this pathophysiological framework lacks a mechanistic explanation of how macroscale synchronous dynamics emerge from alterations of the DG at the microcircuit level. In particular, the relative contribution of developmentally defined subpopulations of adult-born (abGCs) and mature (mGCs) granule cells to epileptiform network events remains unknown. To address this question, we optically recorded activity dynamics of identified populations of abGCs and mGCs during interictal epileptiform discharges (IEDs) in mice with chronic TLE. We find that disjoint subsets of IEDs differentially recruit abGC and mGC populations. We used these observations to develop a neural topic modeling framework, under which we find that the epileptic DG network organizes into disjoint, cell-type specific pathological ensembles, a subset of which are recruited by each IED. We found that statistics of this ensemble structure are highly conserved across animals, with abGCs disproportionately driving network activity in the epileptic DG during IEDs. Our results provide the first in vivo characterization of activity dynamics of identified GC subpopulations in the epileptic DG, the first microcircuit-level correlates of IEDs in vivo, and reveal a specific contribution of abGCs to interictal epileptic events.HighlightsWe relate electrographic signatures of epilepsy to microcircuit dynamics at single-cell resolutionThe chronically epileptic dentate gyrus granule cell network is organized in lineage-specific pathological ensemblesA novel generative model framework for ensemble recruitment relates local field potential signatures to microcircuit activation during interictal epileptiform dischargesAdult-born granule cell-dominated ensembles are disproportionately represented among the inferred ensemblesThe most active ensemble during an interictal epileptiform discharge can be decoded directly from the local field potential spectrumThis Latent Ensemble Recruitment model of cell recruitment by interictal events is the first application of Bayesian topic modeling to in vivo two-photon calcium imaging data

scholarly journals LTP at Hilar Mossy Cell-Dentate Granule Cell Synapses Modulates Dentate Gyrus Output by Increasing Excitation/Inhibition Balance

Neuron ◽  
2017 ◽  
Vol 95 (4) ◽  
pp. 928-943.e3 ◽  
Author(s):  
Yuki Hashimotodani ◽  
Kaoutsar Nasrallah ◽  
Kyle R. Jensen ◽  
Andrés E. Chávez ◽  
Daniel Carrera ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Granule Cell ◽  
Dentate Granule Cell ◽  
Mossy Cell

scholarly journals MicroRNA-8 targets the Wingless signaling pathway in the female mosquito fat body to regulate reproductive processes

2015 ◽  
Vol 112 (5) ◽  
pp. 1440-1445 ◽  
Author(s):  
Keira J. Lucas ◽  
Sourav Roy ◽  
Jisu Ha ◽  
Amanda L. Gervaise ◽  
Vladimir A. Kokoza ◽  
...  
Keyword(s):  
Blood Meal ◽  
Molecular Mechanisms ◽  
Fat Body ◽  
Control Strategies ◽  
Functional Characterization ◽  
Target Prediction ◽  
Underlying Mechanism ◽  
Female Mosquito ◽  
Reproductive Events

Female mosquitoes require a blood meal for reproduction, and this blood meal provides the underlying mechanism for the spread of many important vector-borne diseases in humans. A deeper understanding of the molecular mechanisms linked to mosquito blood meal processes and reproductive events is of particular importance for devising innovative vector control strategies. We found that the conserved microRNA miR-8 is an essential regulator of mosquito reproductive events. Two strategies to inhibit miR-8 function in vivo were used for functional characterization: systemic antagomir depletion and spatiotemporal inhibition using the miRNA sponge transgenic method in combination with the yeast transcriptional activator gal4 protein/upstream activating sequence system. Depletion of miR-8 in the female mosquito results in defects related to egg development and deposition. We used a multialgorithm approach for miRNA target prediction in mosquito 3′ UTRs and experimentally verified secreted wingless-interacting molecule (swim) as an authentic target of miR-8. Our findings demonstrate that miR-8 controls the activity of the long-range Wingless (Wg) signaling by regulating Swim expression in the female fat body. We discovered that the miR-8/Wg axis is critical for the proper secretion of lipophorin and vitellogenin by the fat body and subsequent accumulation of these yolk protein precursors by developing oocytes.

scholarly journals Deletion of Jdp2 enhances Slc7a11 expression in Atoh-1 positive cerebellum granule cell progenitors in vivo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chia-Chen Ku ◽  
Kenly Wuputra ◽  
Kohsuke Kato ◽  
Jia-Bin Pan ◽  
Chia-Pei Li ◽  
...  
Keyword(s):  
Granule Cell ◽  
Granule Cells ◽  
Apoptotic Cell ◽  
Redox Homeostasis ◽  
Critical Role ◽  
Glutamate Transporter ◽  
Developmental Abnormalities ◽  
Oxidative Stresses

Abstract Background The cerebellum is the sensitive region of the brain to developmental abnormalities related to the effects of oxidative stresses. Abnormal cerebellar lobe formation, found in Jun dimerization protein 2 (Jdp2)-knockout (KO) mice, is related to increased antioxidant formation and a reduction in apoptotic cell death in granule cell progenitors (GCPs). Here, we aim that Jdp2 plays a critical role of cerebellar development which is affected by the ROS regulation and redox control. Objective Jdp2-promoter-Cre transgenic mouse displayed a positive signal in the cerebellum, especially within granule cells. Jdp2-KO mice exhibited impaired development of the cerebellum compared with wild-type (WT) mice. The antioxidation controlled gene, such as cystine-glutamate transporter Slc7a11, might be critical to regulate the redox homeostasis and the development of the cerebellum. Methods We generated the Jdp2-promoter-Cre mice and Jdp2-KO mice to examine the levels of Slc7a11, ROS levels and the expressions of antioxidation related genes were examined in the mouse cerebellum using the immunohistochemistry. Results The cerebellum of Jdp2-KO mice displayed expression of the cystine-glutamate transporter Slc7a11, within the internal granule layer at postnatal day 6; in contrast, the WT cerebellum mainly displayed Sla7a11 expression in the external granule layer. Moreover, development of the cerebellar lobes in Jdp2-KO mice was altered compared with WT mice. Expression of Slc7a11, Nrf2, and p21Cip1 was higher in the cerebellum of Jdp2-KO mice than in WT mice. Conclusion Jdp2 is a critical regulator of Slc7a11 transporter during the antioxidation response, which might control the growth, apoptosis, and differentiation of GCPs in the cerebellar lobes. These observations are consistent with our previous study in vitro.

Mossy Fiber–Granule Cell Synapses in the Normal and Epileptic Rat Dentate Gyrus Studied With Minimal Laser Photostimulation

1999 ◽  
Vol 82 (4) ◽  
pp. 1883-1894 ◽  
Author(s):  
Péter Molnár ◽  
J. Victor Nadler
Keyword(s):  
Status Epilepticus ◽  
Dentate Gyrus ◽  
Granule Cell ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Hippocampal Formation ◽  
Control Groups ◽  
Small Component ◽  
Fiber Growth ◽  
And Control

Dentate granule cells become synaptically interconnected in the hippocampus of persons with temporal lobe epilepsy, forming a recurrent mossy fiber pathway. This pathway may contribute to the development and propagation of seizures. The physiology of mossy fiber–granule cell synapses is difficult to characterize unambiguously, because electrical stimulation may activate other pathways and because there is a low probability of granule cell interconnection. These problems were addressed by the use of scanning laser photostimulation in slices of the caudal hippocampal formation. Glutamate was released from a caged precursor with highly focused ultraviolet light to evoke action potentials in a small population of granule cells. Excitatory synaptic currents were recorded in the presence of bicuculline. Minimal laser photostimulation evoked an apparently unitary excitatory postsynaptic current (EPSC) in 61% of granule cells from rats that had experienced pilocarpine-induced status epilepticus followed by recurrent mossy fiber growth. An EPSC was also evoked in 13–16% of granule cells from the control groups. EPSCs from status epilepticus and control groups had similar peak amplitudes (∼30 pA), 20–80% rise times (∼1.2 ms), decay time constants (∼10 ms), and half-widths (∼8 ms). The mean failure rate was high (∼70%) in both groups, and in both groups activation of N-methyl-d-aspartate receptors contributed a small component to the EPSC. The strong similarity between responses from the status epilepticus and control groups suggests that they resulted from activation of a similar synaptic population. No EPSC was recorded when the laser beam was focused in the dentate hilus, suggesting that indirect activation of hilar mossy cells contributed little, if at all, to these results. Recurrent mossy fiber growth increases the density of mossy fiber–granule cell synapses in the caudal dentate gyrus by perhaps sixfold, but the new synapses appear to operate very similarly to preexisting mossy fiber–granule cell synapses.

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