scholarly journals Changes in Mint1, a Novel Synaptic Protein, After Transient Global Ischemia in Mouse Hippocampus

2000 ◽  
Vol 20 (10) ◽  
pp. 1437-1445 ◽  
Author(s):  
Hiroyuki Nishimura ◽  
Tomohiro Matsuyama ◽  
Kyoko Obata ◽  
Yatsuka Nakajima ◽  
Hideto Kitano ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Synaptic Vesicle ◽  
Entorhinal Cortex ◽  
Pyramidal Neurons ◽  
Mossy Fibers ◽  
Global Ischemia ◽  
Mouse Hippocampus ◽  
Ca3 Pyramidal Neurons ◽  
Neuronal Transmission ◽  
Transient Global Ischemia

Mints (munc18-interacting proteins) are novel multimodular adapter proteins in membrane transport and organization. Mint1, a neuronal isoform, is involved in synaptic vesicle exocytosis. Its potential effects on development of ischemic damage to neurons have not yet been evaluated. The authors examined changes in mint1 and other synaptic proteins by immunohistochemistry after transient global ischemia in mouse hippocampus. In sham-ischemic mice, immunoreactivity for mint1 was rich in fibers projecting from the entorhinal cortex to the hippocampus and in the mossy fibers linking the granule cells of the dentate gyrus to CA3 pyramidal neurons. Munc18-1, a binding partner of mint1, was distributed uniformly throughout the hippocampus, and synaptophysin 2, a synaptic vesicle protein, was localized mainly in mossy fibers. After transient global ischemia, mint1 immunoreactivity in mossy fibers was dramatically decreased at 1 day of reperfusion but actually showed enhancement at 3 days. However, munc18-1 and synaptophysin 2 were substantially expressed in the same region throughout the reperfusion period. These findings suggest that mint1 participates in neuronal transmission along the excitatory pathway linking the entorhinal cortex to CA3 in the hippocampus. Because mint1 was transiently decreased in the mossy fiber projection after ischemia, functional impairment of neuronal transmission in the projection from the dentate gyrus to CA3 pyramidal neurons might be involved in delayed neuronal death.

scholarly journals Reduced GluN1 in mouse dentate gyrus is associated with CA3 hyperactivity and psychosis-like behaviors

2018 ◽  
Vol 25 (11) ◽  
pp. 2832-2843 ◽  
Author(s):  
Amir Segev ◽  
Masaya Yanagi ◽  
Daniel Scott ◽  
Sarah A. Southcott ◽  
Jacob M. Lister ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Basolateral Amygdala ◽  
Pyramidal Neurons ◽  
Mossy Fibers ◽  
Model Systems ◽  
Memory Processing ◽  
Hippocampal Subfields ◽  
Whole Cell Patch Clamp ◽  
Hippocampal Activity

Abstract Recent findings from in vivo-imaging and human post-mortem tissue studies in schizophrenic psychosis (SzP), have demonstrated functional and molecular changes in hippocampal subfields that can be associated with hippocampal hyperexcitability. In this study, we used a subfield-specific GluN1 knockout mouse with a disease-like molecular perturbation expressed only in hippocampal dentate gyrus (DG) and assessed its association with hippocampal physiology and psychosis-like behaviors. First, we used whole-cell patch-clamp recordings to measure the physiological changes in hippocampal subfields and cFos immunohistochemistry to examine cellular excitability. DG-GluN1 KO mice show CA3 cellular hyperactivity, detected using two approaches: (1) increased excitatory glutamate transmission at mossy fibers (MF)-CA3 synapses, and (2) an increased number of cFos-activated pyramidal neurons in CA3, an outcome that appears to project downstream to CA1 and basolateral amygdala (BLA). Furthermore, we examined psychosis-like behaviors and pathological memory processing; these show an increase in fear conditioning (FC), a reduction in prepulse inhibition (PPI) in the KO animal, along with a deterioration in memory accuracy with Morris Water Maze (MWM) and reduced social memory (SM). Moreover, with DREADD vectors, we demonstrate a remarkably similar behavioral profile when we induce CA3 hyperactivity. These hippocampal subfield changes could provide the basis for the observed increase in human hippocampal activity in SzP, based on the shared DG-specific GluN1 reduction. With further characterization, these animal model systems may serve as targets to test psychosis mechanisms related to hippocampus and assess potential hippocampus-directed treatments.

Generation and propagation of epileptiform discharges in a combined entorhinal cortex/hippocampal slice

1993 ◽  
Vol 70 (5) ◽  
pp. 1962-1974 ◽  
Author(s):  
A. Rafiq ◽  
R. J. DeLorenzo ◽  
D. A. Coulter
Keyword(s):  
Dentate Gyrus ◽  
Entorhinal Cortex ◽  
Mossy Fibers ◽  
Epileptiform Discharge ◽  
Intracellular Recordings ◽  
Tonic Component ◽  
Ca1 Neurons ◽  
Repeated Stimulation ◽  
Epileptiform Discharges ◽  
Reciprocal Connections

1. The development of epileptiform discharges in response to tetanic stimulation of the Schaeffer collaterals was studied by using extracellular field potential recordings in CA1, CA3, dentate gyrus, and entorhinal cortex and intracellular recordings in CA1 neurons in rat hippocampal-parahippocampal slices, which were cut so as to maintain reciprocal connections between entorhinal cortex and hippocampus in vitro. 2. The first type of epileptiform discharge to develop was an immediate afterdischarge, which grew in duration and amplitude with repeated stimulation trains at 10-min intervals, until it plateaued after five to nine trains at 40-s duration, on average. This afterdischarge, when fully developed, consisted of an early, high frequency tonic component, followed by a later, lower frequency clonic component. Fully developed primary afterdischarges were all-or-none, in that they had a definite threshold, and varied little in amplitude or duration when activated by threshold or suprathreshold stimulation. The primary discharge could be recorded simultaneously throughout the hippocampal-parahippocampal slice, providing evidence for the intact reciprocal connections between hippocampus and entorhinal cortex. Intracellular recordings in CA1 neurons revealed that during the tonic phase of the afterdischarge, neurons were depolarized by 15-30 mV and gradually repolarized during the clonic component. 3. After full development of the primary afterdischarge, a delayed secondary epileptiform discharge began to appear after five to nine stimulation trains. This late discharge began 2-5 min after the stimulation train and progressed in amplitude and duration with repeated stimulation, in some cases to 2-3 h long self-sustained epileptiform discharges. Like the primary afterdischarge, the secondary discharge could be recorded simultaneously throughout the hippocampal-parahippocampal slice, and individual bursts comprising the secondary discharge occurred at earliest latency in the dentate gyrus, followed by activation in CA3, CA1, and finally in the entorhinal cortex. Intracellular recordings in CA1 neurons established that the secondary discharge occurred without an accompanying depolarization. Rather, it appeared as synaptic bursts developing in an escalating frequency barrage, initiated 2-5 min after the primary afterdischarge. 4. Lesioning studies were conducted to begin determining the site of origin of the secondary epileptiform discharge. After appearance of the secondary discharge, the mossy fibers were cut. This lesion abolished the secondary discharge but did not block the primary afterdischarge. Moving the stimulating electrodes from the Schaeffer collaterals to the mossy fibers proximal to the cut reestablished a truncated secondary discharge. In a second lesioning experiment, a cut was made through the subicular region of the hippocampal-parahippocampal slice before the onset of stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Calcium Signaling at Single Mossy Fiber Presynaptic Terminals in the Rat Hippocampus

2002 ◽  
Vol 87 (2) ◽  
pp. 1132-1137 ◽  
Author(s):  
Yong Liang ◽  
Li-Lian Yuan ◽  
Daniel Johnston ◽  
Richard Gray
Keyword(s):  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Imaging Techniques ◽  
Cyclopiazonic Acid ◽  
Mossy Fibers ◽  
Ruthenium Red ◽  
Experimental Conditions ◽  
Intracellular Ca ◽  
Ca3 Pyramidal Neurons ◽  
Calcium Green

We investigated internal Ca2+ release at mossy fiber synapses on CA3 pyramidal neurons (mossy fiber terminals, MFTs) in the hippocampus. Presynaptic Ca2+ influx was induced by giving a brief train of 20 stimuli at 100 Hz to the mossy fiber pathway. Using Ca2+ imaging techniques, we recorded the Ca2+ response as Δ F/ F,which increased rapidly with stimulation, but was often accompanied by a delayed peak that occurred after the train. The rise in presynaptic [Ca2+] could be completely blocked by application of 400 μM Cd2+. Furthermore, the evoked Ca2+ signals were reduced by group II mGluR agonists. Under the same experimental conditions, we investigated the effects of several agents on MFTs that disrupt regulation of intracellular Ca2+ stores resulting in depletion of internal Ca2+. We found that ryanodine, cyclopiazonic acid, thapsigargin, and ruthenium red all decreased both the early and the delayed increase in the Ca2+signals. We applied d,l-2-amino-5-phosphonovaleric acid (d,l-APV; 50 μM) and 6,7-Dinitroquinoxaline-2,3-dione (DNQX; 20 μM) to exclude the action of N-methyl-d-aspartate (NMDA) and non-NMDA receptors. Experiments with alternative lower affinity indicators for Ca2+ (fura-2FF and calcium green-2) and the transient K+ channel blocker, 4-aminopyridine were performed to control for the possible saturation of fura-2. Taken together, these results strongly support the hypothesis that the recorded terminals were from the mossy fibers of the dentate gyrus and suggest that a portion of the presynaptic Ca2+signal in response to brief trains of stimuli is due to release of Ca2+ from internal stores.

Acupuncture increases cell proliferation in dentate gyrus after transient global ischemia in gerbils

2001 ◽  
Vol 297 (1) ◽  
pp. 21-24 ◽  
Author(s):  
Ee-Hwa Kim ◽  
Youn-Jung Kim ◽  
Hee Jae Lee ◽  
Youngbuhm Huh ◽  
Joo-Ho Chung ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Dentate Gyrus ◽  
Global Ischemia ◽  
Transient Global Ischemia

scholarly journals Action potential counting at giant mossy fiber terminals gates information transfer in the hippocampus

2018 ◽  
Vol 115 (28) ◽  
pp. 7434-7439 ◽  
Author(s):  
Simon Chamberland ◽  
Yulia Timofeeva ◽  
Alesya Evstratova ◽  
Kirill Volynski ◽  
Katalin Tóth
Keyword(s):  
Action Potential ◽  
Granule Cell ◽  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Glutamate Release ◽  
Mossy Fibers ◽  
Action Potential Firing ◽  
Potential Firing ◽  
Ca3 Pyramidal Neurons ◽  
Calbindin D

Neuronal communication relies on action potential discharge, with the frequency and the temporal precision of action potentials encoding information. Hippocampal mossy fibers have long been recognized as conditional detonators owing to prominent short-term facilitation of glutamate release displayed during granule cell burst firing. However, the spiking patterns required to trigger action potential firing in CA3 pyramidal neurons remain poorly understood. Here, we show that glutamate release from mossy fiber terminals triggers action potential firing of the target CA3 pyramidal neurons independently of the average granule cell burst frequency, a phenomenon we term action potential counting. We find that action potential counting in mossy fibers gates glutamate release over a broad physiological range of frequencies and action potential numbers. Using rapid Ca2+ imaging we also show that the magnitude of evoked Ca2+ influx stays constant during action potential trains and that accumulated residual Ca2+ is gradually extruded on a time scale of several hundred milliseconds. Using experimentally constrained 3D model of presynaptic Ca2+ influx, buffering, and diffusion, and a Monte Carlo model of Ca2+-activated vesicle fusion, we argue that action potential counting at mossy fiber boutons can be explained by a unique interplay between Ca2+ dynamics and buffering at release sites. This is largely determined by the differential contribution of major endogenous Ca2+ buffers calbindin-D28K and calmodulin and by the loose coupling between presynaptic voltage-gated Ca2+ channels and release sensors and the relatively slow Ca2+ extrusion rate. Taken together, our results identify a previously unexplored information-coding mechanism in the brain.

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