scholarly journals Enriched Environment Modulates Sharp Wave-Ripple (SPW-R) Activity in Hippocampal Slices

2021 ◽  
Vol 15 ◽  
Author(s):  
Lucie Landeck ◽  
Martin E. Kaiser ◽  
Dimitri Hefter ◽  
Andreas Draguhn ◽  
Martin Both
Keyword(s):  
Hippocampal Slices ◽  
Behavioral Flexibility ◽  
Pyramidal Cells ◽  
Enriched Environment ◽  
Cognitive Behavioral ◽  
Network Activity ◽  
Inhibitory Neurons ◽  
Synaptic Inhibition ◽  
Dependent Manner ◽  
Sharp Wave

Behavioral flexibility depends on neuronal plasticity which forms and adapts the central nervous system in an experience-dependent manner. Thus, plasticity depends on interactions between the organism and its environment. A key experimental paradigm for studying this concept is the exposure of rodents to an enriched environment (EE), followed by studying differences to control animals kept under standard conditions (SC). While multiple changes induced by EE have been found at the cellular-molecular and cognitive-behavioral levels, little is known about EE-dependent alterations at the intermediate level of network activity. We, therefore, studied spontaneous network activity in hippocampal slices from mice which had previously experienced EE for 10–15 days. Compared to control animals from standard conditions (SC) and mice with enhanced motor activity (MC) we found several differences in sharp wave-ripple complexes (SPW-R), a memory-related activity pattern. Sharp wave amplitude, unit firing during sharp waves, and the number of superimposed ripple cycles were increased in tissue from the EE group. On the other hand, spiking precision with respect to the ripple oscillations was reduced. Recordings from single pyramidal cells revealed a reduction in synaptic inhibition during SPW-R together with a reduced inhibition-excitation ratio. The number of inhibitory neurons, including parvalbumin-positive interneurons, was unchanged. Altered activation or efficacy of synaptic inhibition may thus underlie changes in memory-related network activity patterns which, in turn, may be important for the cognitive-behavioral effects of EE exposure.

scholarly journals Extracellular GABA waves regulate coincidence detection in excitatory circuits

2020 ◽  
Author(s):  
Sergiy Sylantyev ◽  
Leonid P. Savtchenko ◽  
Nathanael O’Neill ◽  
Dmitri A. Rusakov
Keyword(s):  
Strong Dependence ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Underlying Mechanism ◽  
Brain Network ◽  
Coincidence Detection ◽  
Network Activity ◽  
Gaba Uptake ◽  
Signal Integration ◽  
Feed Forward

AbstractCoincidence detection of excitatory inputs by principal neurons underpins the rules of signal integration and Hebbian plasticity in the brain. In the hippocampal circuitry, detection fidelity is thought to depend on the GABAergic synaptic input through a feed-forward inhibitory circuit also involving the hyperpolarization-activated Ih current. However, afferent connections often bypass feed-forward circuitry, suggesting that a different GABAergic mechanism might control coincidence detection in such cases. To test whether fluctuations in the extracellular GABA concentration [GABA] could play a regulatory role here, we use a GABA ‘sniffer’ patch in acute hippocampal slices of the rat and document strong dependence of [GABA] on network activity. We find that blocking GABAergic signalling strongly reduces the coincidence detection window of direct excitatory inputs to pyramidal cells whereas increasing [GABA] through GABA uptake blockade expands it. The underlying mechanism involves membrane-shunting tonic GABAA receptor current; it does not have to rely on Ih but depends strongly on the neuronal GABA transporter GAT-1. We use dendrite-soma dual patch-clamp recordings to show that the strong effect of membrane shunting on coincidence detection relies on nonlinear amplification of changes in the decay of dendritic synaptic currents when they reach the soma. Our results suggest that, by dynamically regulating extracellular GABA, brain network activity can optimise signal integration rules in local excitatory circuits.

Agent-selective Effects of Volatile Anesthetics on GABAAReceptor–mediated Synaptic Inhibition in Hippocampal Interneurons

2001 ◽  
Vol 94 (2) ◽  
pp. 340-347 ◽  
Author(s):  
Koichi Nishikawa ◽  
M. Bruce MacIver
Keyword(s):  
Gabaa Receptor ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Volatile Anesthetics ◽  
Stratum Radiatum ◽  
Synaptic Inhibition ◽  
Gamma Aminobutyric Acid ◽  
Ca1 Region ◽  
Whole Cell Patch Clamp ◽  
Cortical Regions

Background A relatively small number of inhibitory interneurons can control the excitability and synchronization of large numbers of pyramidal cells in hippocampus and other cortical regions. Thus, anesthetic modulation of interneurons could play an important role for the maintenance of anesthesia. The aim of this study was to compare effects produced by volatile anesthetics on inhibitory postsynaptic currents (IPSCs) of rat hippocampal interneurons. Methods Pharmacologically isolated gamma-aminobutyric acid type A (GABAA) receptor-mediated IPSCs were recorded with whole cell patch-clamp techniques in visually identified interneurons of rat hippocampal slices. Neurons located in the stratum radiatum-lacunosum moleculare of the CA1 region were studied. The effects of clinically relevant concentrations (1.0 rat minimum alveolar concentration) of halothane, enflurane, isoflurane, and sevoflurane were compared on kinetics of both stimulus-evoked and spontaneous GABAA receptor-mediated IPSCs in interneurons. Results Halothane (1.2 vol% approximately 0.35 mm), enflurane (2.2 vol% approximately 0.60 mm), isoflurane (1.4 vol% approximately 0.50 mm), and sevoflurane (2.7 vol% approximately 0.40 mm) preferentially depressed evoked IPSC amplitudes to 79.8 +/- 9.3% of control (n = 5), 38.2 +/- 8.6% (n = 6), 52.4 +/- 8.4% (n = 5), and 46.1 +/- 16.0% (n = 8), respectively. In addition, all anesthetics differentially prolonged the decay time constant of evoked IPSCs to 290.1 +/- 33.2% of control, 423.6 +/- 47.1, 277.0 +/- 32.2, and 529 +/- 48.5%, respectively. The frequencies of spontaneous IPSCs were increased by all anesthetics (twofold to threefold). Thus, the total negative charge transfer mediated by GABAA receptors between synaptically connected interneurons was enhanced by all anesthetics. Conclusions Volatile anesthetics differentially enhanced GABAA receptor-mediated synaptic inhibition in rat hippocampal interneurons, suggesting that hippocampal interneuron circuits are depressed by these anesthetics in an agent-specific manner.

scholarly journals Induced sharp wave-ripple complexes in the absence of synaptic inhibition in mouse hippocampal slices

2005 ◽  
Vol 563 (3) ◽  
pp. 663-670 ◽  
Author(s):  
Volker Nimmrich ◽  
Nikolaus Maier ◽  
Dietmar Schmitz ◽  
Andreas Draguhn
Keyword(s):  
Hippocampal Slices ◽  
Synaptic Inhibition ◽  
Sharp Wave

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.

Transient Depression of Excitatory Synapses on Interneurons Contributes to Epileptiform Bursts During Gamma Oscillations in the Mouse Hippocampal Slice

2005 ◽  
Vol 94 (2) ◽  
pp. 1225-1235 ◽  
Author(s):  
Roger D. Traub ◽  
Isabel Pais ◽  
Andrea Bibbig ◽  
Fiona E.N. LeBeau ◽  
Eberhard H. Buhl ◽  
...  
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
Network Activity ◽  
Excitatory Synapses ◽  
Metabotropic Glutamate ◽  
Gamma Frequency ◽  
Gamma Rhythm ◽  
Fast Oscillations

Persistent gamma frequency (30–70 Hz) network oscillations occur in hippocampal slices under conditions of metabotropic glutamate receptor (mGluR) activation. Excessive mGluR activation generated a bistable pattern of network activity during which epochs of gamma oscillations of increasing amplitude were terminated by synchronized bursts and very fast oscillations (>70 Hz). We provide experimental evidence that, during this behavior, pyramidal cell-to-interneuron synaptic depression takes place, occurring spontaneously during the gamma rhythm and associated with the onset of epileptiform bursts. We further provide evidence that excitatory postsynaptic potentials (EPSPs) in pyramidal cells are potentiated during the interburst gamma oscillation. When these two types of synaptic plasticity are incorporated, phenomenologically, into a network model previously shown to account for many features of persistent gamma oscillations, we find that epochs of gamma do indeed alternate with epochs of very fast oscillations and epileptiform bursts. Thus the same neuronal network can generate either gamma oscillations or epileptiform bursts, in a manner depending on the degree of network drive and network-induced fluctuations in synaptic efficacies.

Calexcitin interaction with neuronal ryanodine receptors

1999 ◽  
Vol 341 (2) ◽  
pp. 423-433 ◽  
Author(s):  
Thomas J. NELSON ◽  
Wei-Qin ZHAO ◽  
Shauna YUAN ◽  
Antonella FAVIT ◽  
Lucas POZZO-MILLER ◽  
...  
Keyword(s):  
Ryanodine Receptors ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Dependent Manner ◽  
Proximate Cause ◽  
Calcium Dependent ◽  
Amino Acid Peptide ◽  
Ca1 Pyramidal Cells ◽  
Endogenous Modulator ◽  
Relative Proximity

Calexcitin (CE), a Ca2+- and GTP-binding protein, which is phosphorylated during memory consolidation, is shown here to co-purify with ryanodine receptors (RyRs) and bind to RyRs in a calcium-dependent manner. Nanomolar concentrations of CE released up to 46% of the 45Ca label from microsomes preloaded with 45CaCl2. This release was Ca2+-dependent and was blocked by antibodies against the RyR or CE, by the RyR inhibitor dantrolene, and by a seven-amino-acid peptide fragment corresponding to positions 4689-4697 of the RyR, but not by heparin, an Ins(1,4,5)P3-receptor antagonist. Anti-CE antibodies, in the absence of added CE, also blocked Ca2+ release elicited by ryanodine, suggesting that the CE and ryanodine binding sites were in relative proximity. Calcium imaging with bis-fura-2 after loading CE into hippocampal CA1 pyramidal cells in hippocampal slices revealed slow, local calcium transients independent of membrane depolarization. Calexcitin also released Ca2+ from liposomes into which purified RyR had been incorporated, indicating that CE binding can be a proximate cause of Ca2+ release. These results indicated that CE bound to RyRs and suggest that CE may be an endogenous modulator of the neuronal RyR.

Common excitatory synaptic inputs to electrically connected cortical fast-spiking cell networks

2013 ◽  
Vol 110 (4) ◽  
pp. 795-806 ◽  
Author(s):  
Takeshi Otsuka ◽  
Yasuo Kawaguchi
Keyword(s):  
Pyramidal Cells ◽  
Network Activity ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Cell Network ◽  
Network State ◽  
State Dependent ◽  
Fast Spiking ◽  
Chemical Synapses ◽  
Cell Networks

Cortical fast-spiking (FS) interneurons are electrically interconnected through gap junctions and form dendritic net structures extending over different functional columns. Here we investigated how pyramidal cells regulate FS cell network activity. Using paired recordings and glutamate puff stimulations, we found that FS cell pairs connected by electrical synapses shared common inputs from surrounding pyramidal cells more frequently than those unconnected or connected only by chemical synapses. Experimental and simulation results suggest that activity spread evoked by common inputs to electrically connected FS cells depends on network state. When cells were in the depolarized state, common inputs to electrically connected cells enhanced spike induction and induced inhibitory effects in surrounding FS cells. By contrast, in the hyperpolarized state, either sub- or suprathreshold inputs produced depolarizing potentials in nearby cells. Our results suggest that globally connected FS cell networks are locally regulated by pyramidal cells in an electrical connection- and network state-dependent manner.

scholarly journals Learning-induced sequence reactivation during sharp-wave ripples: a computational study

2017 ◽  
Author(s):  
Paola Malerba ◽  
Katya Tsimring ◽  
Maxim Bazhenov
Keyword(s):  
Computational Study ◽  
Activity Patterns ◽  
Pyramidal Cells ◽  
Learning Task ◽  
Network Activity ◽  
Sharp Wave ◽  
High Frequency Oscillations ◽  
Excitatory Activity ◽  
Hippocampal Network ◽  
Synaptic Changes

AbstractDuring sleep, memories formed during the day are consolidated in a dialogue between cortex and hippocampus. The reactivation of specific neural activity patterns – replay – during sleep has been observed in both structures and is hypothesized to represent a neuronal substrate of consolidation. In the hippocampus, replay happens during sharp wave – ripples (SWR), short bouts of excitatory activity in area CA3 which induce high frequency oscillations in area CA1. In particular, recordings of hippocampal cells which spike at a specific location (‘place cells’) show that recently learned trajectories are reactivated during SWR in the following sleep SWR. Despite the importance of sleep replay, its underlying neural mechanisms are still poorly understood.We developed a model of SWR activity, to study the effects of learning-induced synaptic changes on spontaneous sequence reactivation during SWR. The model implemented a paradigm including three epochs: Pre-sleep, learning and Post-sleep activity. We first tested the effects of learning on the hippocampal network activity through changes in a minimal number of synapses connecting selected pyramidal cells. We then introduced an explicit trajectory-learning task to the model, to obtain behavior-induced synaptic changes. The model revealed that the recently learned trajectory reactivates during sleep more often than other trajectories in the training field. The study predicts that the gain of reactivation rate during sleep following vs sleep preceding learning for a trained sequence of pyramidal cells depends on Pre-sleep activation of the same sequence, and on the amount of trajectory repetitions included in the training phase.

Endocannabinoid system in the neurodevelopment of GABAergic interneurons: implications for neurological and psychiatric disorders

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Chang-geng Song ◽  
Xin Kang ◽  
Fang Yang ◽  
Wan-qing Du ◽  
Jia-jia Zhang ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Endocannabinoid System ◽  
Autism Spectrum ◽  
Network Activity ◽  
Inhibitory Neurons ◽  
Gabaergic Interneurons ◽  
Neural Stem Progenitor Cells ◽  
The Central Nervous System ◽  
Interneuron Development

Abstract In mature mammalian brains, the endocannabinoid system (ECS) plays an important role in the regulation of synaptic plasticity and the functioning of neural networks. Besides, the ECS also contributes to the neurodevelopment of the central nervous system. Due to the increase in the medical and recreational use of cannabis, it is inevitable and essential to elaborate the roles of the ECS on neurodevelopment. GABAergic interneurons represent a group of inhibitory neurons that are vital in controlling neural network activity. However, the role of the ECS in the neurodevelopment of GABAergic interneurons remains to be fully elucidated. In this review, we provide a brief introduction of the ECS and interneuron diversity. We focus on the process of interneuron development and the role of ECS in the modulation of interneuron development, from the expansion of the neural stem/progenitor cells to the migration, specification and maturation of interneurons. We further discuss the potential implications of the ECS and interneurons in the pathogenesis of neurological and psychiatric disorders, including epilepsy, schizophrenia, major depressive disorder and autism spectrum disorder.

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