scholarly journals Release probability increases towards distal dendrites boosting high-frequency signal transfer in the rodent hippocampus

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Thomas P Jensen ◽  
Olga Kopach ◽  
James P Reynolds ◽  
Leonid P Savtchenko ◽  
Dmitri A Rusakov
Keyword(s):  
High Frequency ◽  
Glutamate Release ◽  
Hippocampal Slices ◽  
Network Activity ◽  
Signal Transfer ◽  
High Frequency Signal ◽  
Release Probability ◽  
Acute Hippocampal Slices ◽  
Rats And Mice ◽  
Trace Formation

Dendritic integration of synaptic inputs involves their increased electrotonic attenuation at distal dendrites, which can be counterbalanced by the increased synaptic receptor density. However, during network activity, the influence of individual synapses depends on their release fidelity, the dendritic distribution of which remains poorly understood. Here, we employed classical optical quantal analyses and a genetically encoded optical glutamate sensor in acute hippocampal slices of rats and mice to monitor glutamate release at CA3-CA1 synapses. We find that their release probability increases with greater distances from the soma. Similar-fidelity synapses tend to group together, whereas release probability shows no trends regarding the branch ends. Simulations with a realistic CA1 pyramidal cell hosting stochastic synapses suggest that the observed trends boost signal transfer fidelity, particularly at higher input frequencies. Because high-frequency bursting has been associated with learning, the release probability pattern we have found may play a key role in memory trace formation.

scholarly journals Release probability increases towards distal dendrites boosting high-frequency signal transfer

2020 ◽  
Author(s):  
Thomas P. Jensen ◽  
Olga Kopach ◽  
Leonid P. Savchenko ◽  
James P. Reynolds ◽  
Dmitri A. Rusakov
Keyword(s):  
High Frequency ◽  
Memory Trace ◽  
Hippocampal Slices ◽  
Network Activity ◽  
Signal Transfer ◽  
High Frequency Signal ◽  
Release Probability ◽  
Synaptic Receptor ◽  
Acute Hippocampal Slices ◽  
Trace Formation

ABSTRACTDendritic integration of synaptic inputs entangles their increased electrotonic attenuation at distal dendrites, which can be counterbalanced by the increased synaptic receptor density. However, during sustained network activity the influence of individual synapses depends on their release properties. How these properties are distributed along dendrites remains poorly understood. Here, we employed classical optical quantal analyses and a genetically encoded optical glutamate sensor in acute hippocampal slices to monitor release at CA3-CA1 synapses. We find that their release probability increases with greater distances from the soma. Similar-fidelity synapses tend to group together whereas release probability shows no trends regarding the within-branch position. Simulations with a realistic CA1 pyramidal cell hosting stochastic synapses suggest that the observed trends boost signal transfer fidelity, particularly at higher input frequencies. Because high-frequency bursting has been associated with learning, the release probability pattern we have found may play a key role in memory trace formation.

scholarly journals APP and APLP2 interact with the synaptic release machinery and facilitate transmitter release at hippocampal synapses

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Tomas Fanutza ◽  
Dolores Del Prete ◽  
Michael J Ford ◽  
Pablo E Castillo ◽  
Luciano D’Adamio
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transmitter Release ◽  
Glutamate Release ◽  
Hippocampal Slices ◽  
Synaptic Release ◽  
Hippocampal Synapses ◽  
A Cell ◽  
Acute Hippocampal Slices

The amyloid precursor protein (APP), whose mutations cause familial Alzheimer’s disease, interacts with the synaptic release machinery, suggesting a role in neurotransmission. Here we mapped this interaction to the NH2-terminal region of the APP intracellular domain. A peptide encompassing this binding domain -named JCasp- is naturally produced by a γ-secretase/caspase double-cut of APP. JCasp interferes with the APP-presynaptic proteins interaction and, if linked to a cell-penetrating peptide, reduces glutamate release in acute hippocampal slices from wild-type but not APP deficient mice, indicating that JCasp inhibits APP function.The APP-like protein-2 (APLP2) also binds the synaptic release machinery. Deletion of APP and APLP2 produces synaptic deficits similar to those caused by JCasp. Our data support the notion that APP and APLP2 facilitate transmitter release, likely through the interaction with the neurotransmitter release machinery. Given the link of APP to Alzheimer’s disease, alterations of this synaptic role of APP could contribute to dementia.

Copper Plating Method on Flat Surface for High Frequency Signal Transfer

2005 ◽  
Vol 44 (9A) ◽  
pp. 6719-6725 ◽  
Author(s):  
Koichi Hontake ◽  
Yasuhiro Wakizaka ◽  
Akihiko Furuya ◽  
Daisuke Uchida ◽  
Koichiro Kuribayashi ◽  
...  
Keyword(s):  
High Frequency ◽  
Flat Surface ◽  
Copper Plating ◽  
Signal Transfer ◽  
Frequency Signal ◽  
High Frequency Signal ◽  
Plating Method

Abstract TP281: Increased Susceptibility to Excitotoxic Injury in Rat Hippocampal Slices Exposed to Intermittent Hypoxia

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Rekha Jagadapillai ◽  
Nicholas Mellen ◽  
Leroy R Sachleben ◽  
Evelyne Gozal
Keyword(s):  
Intermittent Hypoxia ◽  
Glutamate Release ◽  
Hippocampal Slices ◽  
Optical Recording ◽  
Network Activity ◽  
Viable Cells ◽  
High K ◽  
Obstructive Sleep ◽  
Increased Risk ◽  
Glutamate Homeostasis

Introduction: The effect of sustained hypoxia (SH) on brain metabolism has been well studied. However less is known about intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), associated with increased risk for stroke, outcome severity and functional consequences. Hypothesis: Impaired glutamate homeostasis after IH may underlie increased brain vulnerability to stroke-induced excitotoxicity. Methods: P4 organotypic rat hippocampal slices cultured for 7 days, were exposed for 7 additional days to IH (alternating 2 min 5% O2 - 15 min 21% O2), SH (5% O2) or normoxia (RA; 21% O2), followed by 3 glutamate challenges (first and last 200 μM, 15 min, emulating a physiological stimulus; second, 10 mM, 10 min, emulating stroke-induced excitotoxicity). Viability was assessed by propidium iodide (PI) uptake at baseline then after each glutamate challenge to assess whether hypoxia impairs the response to physiological or excitotoxic glutamate release. Glial GFAP, neuronal MAP2, EAAT1 and EAAT2 glutamate transporters expression was assessed by immunohistochemistry. Spontaneous and evoked Ca2+ transient activity was assessed in Fluo-8LTM AM loaded slices, by optical recording of Ca2+ spikes proximal to a bipolar stimulating electrode, before and after each of 3 single 2 ms stimuli (0.6 mA). Ca2+ transients after high K+ were used to determine the total number of viable cells. Results: Viability, GFAP, MAP2, EAAT1 and EAAT2 expression and basal Ca2+ spikes activity significantly decreased in IH. The number of neurons with spikes evoked within 500 ms of stimuli was not significantly different, but RA evoked responses were more tightly clustered. Residual network activity, assessed by number of neurons with spikes 500 ms post stimulus, was significantly different RA>SH>IH. Overall number of spiking cells after high K+, representing total viable cells, confirmed the viability data obtained with PI staining. Conclusions: IH is more detrimental to cell survival and glutamate homeostasis than SH, suggesting that in addition to vascular changes, impaired glutamate homeostasis may increase OSA patients’ susceptibility to ischemic events.

scholarly journals Coincident Glutamatergic and Cholinergic Inputs Transiently Depress Glutamate Release at Rat Schaffer Collateral Synapses

2007 ◽  
Vol 97 (6) ◽  
pp. 4108-4119 ◽  
Author(s):  
Keith E. Gipson ◽  
Mark F. Yeckel
Keyword(s):  
Acetylcholine Receptors ◽  
Glutamate Release ◽  
Acetylcholinesterase Inhibitor ◽  
Hippocampal Slices ◽  
Medial Septum ◽  
Network Activity ◽  
Stratum Radiatum ◽  
Hippocampal Function ◽  
Schaffer Collateral ◽  
Single Receptor

The mammalian hippocampus, together with subcortical and cortical areas, is responsible for some forms of learning and memory. Proper hippocampal function depends on the highly dynamic nature of its circuitry, including the ability of synapses to change their strength for brief to long periods of time. In this study, we focused on a transient depression of glutamatergic synaptic transmission at Schaffer collateral synapses in acute hippocampal slices. The depression of evoked excitatory postsynaptic current (EPSC) amplitudes, herein called transient depression, follows brief trains of synaptic stimulation in stratum radiatum of CA1 and lasts for 2–3 min. Depression results from a decrease in presynaptic glutamate release, as NMDA-receptor–mediated EPSCs and composite EPSCs are depressed similarly and depression is accompanied by an increase in the paired-pulse ratio. Transient depression is prevented by blockade of metabotropic glutamate and acetylcholine receptors, presumably located presynaptically. These two receptor types—acting together—cause depression. Blockade of a single receptor type necessitates significantly stronger conditioning trains for triggering depression. Addition of an acetylcholinesterase inhibitor enables depression from previously insufficient conditioning trains. Furthermore, a strong coincident, but not causal, relationship existed between presynaptic depression and postsynaptic internal Ca2+ release, emphasizing the potential importance of functional interactions between presynaptic and postsynaptic effects of convergent cholinergic and glutamatergic inputs to CA1. These convergent afferents, one intrinsic to the hippocampus and the other likely originating in the medial septum, may regulate CA1 network activity, the induction of long-term synaptic plasticity, and ultimately hippocampal function.

scholarly journals New Insights and Methods for Recording and Imaging Spontaneous Spreading Depolarizations and Seizure-Like Events in Mouse Hippocampal Slices

2021 ◽  
Vol 15 ◽  
Author(s):  
Yi-Ling Lu ◽  
Helen E. Scharfman
Keyword(s):  
Dentate Gyrus ◽  
Optical Imaging ◽  
Hippocampal Slices ◽  
Extracellular Recording ◽  
Brain Regions ◽  
Optical Signal ◽  
Artificial Cerebrospinal Fluid ◽  
Acute Hippocampal Slices ◽  
Rats And Mice

Spreading depolarization (SD) is a sudden, large, and synchronous depolarization of principal cells which also involves interneurons and astrocytes. It is followed by depression of neuronal activity, and it slowly propagates across brain regions like cortex or hippocampus. SD is considered to be mechanistically relevant to migraine, epilepsy, and traumatic brain injury (TBI), but there are many questions about its basic neurophysiology and spread. Research into SD in hippocampus using slices is often used to gain insight and SD is usually triggered by a focal stimulus with or without an altered extracellular buffer. Here, we optimize an in vitro experimental model allowing us to record SD without focal stimulation, which we call spontaneous. This method uses only an altered extracellular buffer containing 0 mM Mg2+ and 5 mM K+ and makes it possible for simultaneous patch and extracellular recording in a submerged chamber plus intrinsic optical imaging in slices of either sex. We also add methods for quantification and show the quantified optical signal is much more complex than imaging alone would suggest. In brief, acute hippocampal slices were prepared with a chamber holding a submerged slice but with flow of artificial cerebrospinal fluid (aCSF) above and below, which we call interface-like. As soon as slices were placed in the chamber, aCSF with 0 Mg2+/5 K+ was used. Most mouse slices developed SD and did so in the first hour of 0 Mg2+/5 K+ aCSF exposure. In addition, prolonged bursts we call seizure-like events (SLEs) occurred, and the interactions between SD and SLEs suggest potentially important relationships. Differences between rats and mice in different chambers are described. Regarding optical imaging, SD originated in CA3 and the pattern of spread to CA1 and the dentate gyrus was similar in some ways to prior studies but also showed interesting differences. In summary, the methods are easy to use, provide new opportunities to study SD, new insights, and are inexpensive. They support previous suggestions that SD is diverse, and also suggest that participation by the dentate gyrus merits greater attention.

Desynchronization of Glutamate Release Prolongs Synchronous CA3 Network Activity

2007 ◽  
Vol 97 (5) ◽  
pp. 3812-3818 ◽  
Author(s):  
Jethro Jones ◽  
Elizabeth A. Stubblefield ◽  
Timothy A. Benke ◽  
Kevin J. Staley
Keyword(s):  
Glutamate Release ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Network Activity ◽  
Neural Population ◽  
Axon Terminals ◽  
Rate Of Spread ◽  
Hippocampal Ca3 ◽  
Recurrent Collateral

Periodic bursts of activity in the disinhibited in vitro hippocampal CA3 network spread through the neural population by the glutamatergic recurrent collateral axons that link CA3 pyramidal cells. It was previously proposed that these bursts of activity are terminated by exhaustion of releasable glutamate at the recurrent collateral synapses so that the next periodic burst of network activity cannot occur until the supply of glutamate has been replenished. As a test of this hypothesis, the rate of glutamate release at CA3 axon terminals was reduced by substitution of extracellular Ca2+ with Sr2+. Reduction of the rate of glutamate release reduces the rate of depletion and should thereby prolong bursts. Here we demonstrate that Sr2+ substitution prolongs spontaneous bursts in the disinhibited adult CA3 hippocampal slices to 37.2 ± 7.6 (SE) times the duration in control conditions. Sr2+ also decreased the probability of burst initiation and the rate of burst onset, consistent with reduced synchrony of glutamate release and a consequent reduced rate of spread of excitation through the slice. These findings support the supply of releasable glutamate as an important determinant of the probability and duration of synchronous CA3 network activity.

scholarly journals Optical monitoring of glutamate release at multiple synapses in situ detects changes following LTP induction

2019 ◽  
Author(s):  
Olga Kopach ◽  
Kaiyu Zheng ◽  
Dmitri Rusakov
Keyword(s):  
Optical Sensors ◽  
Glutamate Release ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Excitatory Neurotransmitter ◽  
Two Photon ◽  
Photon Excitation ◽  
Term Potentiation ◽  
Before And After ◽  
Acute Hippocampal Slices

Abstract Information processing and memory formation in the brain relies on release of the main excitatory neurotransmitter glutamate from presynaptic axonal specialisations. The classical Hebbian paradigm of synaptic memory, long-term potentiation (LTP) of transmission, has been widely associated with an increase in the postsynaptic receptor current. Whether and to what degree LTP induction also enhances presynaptic glutamate release has been the subject of debate. Here, we took advantage of the recently developed genetically encoded optical sensors of glutamate (iGluSnFr) to monitor its release at CA3-CA1 synapses in acute hippocampal slices, before and after the induction of LTP. We attempted to trace release events at multiple synapses simultaneously, by using two-photon excitation imaging in fast frame-scanning mode. We thus detected a significant increase in the average glutamate signal during potentiation, which lasted for up to 90 min.

Sign in / Sign up

Export Citation Format

Share Document