scholarly journals Cannabinoids attenuate hippocampal gamma oscillations by suppressing excitatory synaptic input onto CA3 pyramidal neurons and fast spiking basket cells

2011 ◽  
Vol 589 (20) ◽  
pp. 4921-4934 ◽  
Author(s):  
Noémi Holderith ◽  
Beáta Németh ◽  
Orsolya I. Papp ◽  
Judit M. Veres ◽  
Gergő A. Nagy ◽  
...  
Keyword(s):  
Synaptic Input ◽  
Pyramidal Neurons ◽  
Gamma Oscillations ◽  
Basket Cells ◽  
Excitatory Synaptic Input ◽  
Fast Spiking ◽  
Ca3 Pyramidal Neurons

scholarly journals An optogenetic method for investigating presynaptic molecular regulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuni Kay ◽  
Bruce E. Herring
Keyword(s):  
Pyramidal Neurons ◽  
Molecular Regulation ◽  
Glutamatergic Synapses ◽  
Experimental Conditions ◽  
Regulatory Pathways ◽  
Genetic Manipulations ◽  
Postsynaptic Protein ◽  
Presynaptic Function ◽  
Synaptotagmin 1 ◽  
Ca3 Pyramidal Neurons

AbstractWhile efficient methods are well established for studying postsynaptic protein regulation of glutamatergic synapses in the mammalian central nervous system, similarly efficient methods are lacking for studying proteins regulating presynaptic function. In the present study, we introduce an optical/electrophysiological method for investigating presynaptic molecular regulation. Here, using an optogenetic approach, we selectively stimulate genetically modified presynaptic CA3 pyramidal neurons in the hippocampus and measure optically-induced excitatory postsynaptic currents produced in unmodified postsynaptic CA1 pyramidal neurons. While such use of optogenetics is not novel, previous implementation methods do not allow basic quantification of the changes in synaptic strength produced by genetic manipulations. We find that incorporating simultaneous recordings of fiber volley amplitude provides a control for optical stimulation intensity and, as a result, creates a metric of synaptic efficacy that can be compared across experimental conditions. In the present study, we utilize our new method to demonstrate that inhibition of synaptotagmin 1 expression in CA3 pyramidal neurons leads to a significant reduction in Schaffer collateral synapse function, an effect that is masked with conventional electrical stimulation. Our hope is that this method will expedite our understanding of molecular regulatory pathways that govern presynaptic function.

Inhibition of Glutamatergic Synaptic Input to Spinal Lamina IIo Neurons by Presynaptic α2-Adrenergic Receptors

2002 ◽  
Vol 87 (4) ◽  
pp. 1938-1947 ◽  
Author(s):  
Yu-Zhen Pan ◽  
De-Pei Li ◽  
Hui-Lin Pan
Keyword(s):  
Receptor Antagonist ◽  
Synaptic Input ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Dorsal Root ◽  
Primary Afferents ◽  
Noradrenergic System ◽  
Analgesic Action ◽  
Adrenergic Agonists ◽  
Excitatory Synaptic Input

Activation of spinal α2-adrenergic receptors by the descending noradrenergic system and α2-adrenergic agonists produces analgesia. However, the sites and mechanisms of the analgesic action of spinally administered α2-adrenergic receptor agonists such as clonidine are not fully known. The dorsal horn neurons in the outer zone of lamina II (lamina IIo) are important for processing nociceptive information from C-fiber primary afferents. In the present study, we tested a hypothesis that activation of presynaptic α2-adrenergic receptors by clonidine inhibits the excitatory synaptic input to lamina IIo neurons. Whole cell voltage-clamp recordings were performed on visualized lamina IIo neurons in the spinal cord slice of rats. The miniature excitatory postsynaptic currents (mEPSCs) were recorded in the presence of tetrodotoxin, bicuculline, and strychnine. The evoked EPSCs were obtained by electrical stimulation of the dorsal root entry zone or the attached dorsal root. Both mEPSCs and evoked EPSCs were abolished by application of 6-cyano-7-nitroquinoxaline-2,3-dione. Clonidine (10 μM) significantly decreased the frequency of mEPSCs from 5.8 ± 0.9 to 2.7 ± 0.6 Hz (means ± SE) without altering the amplitude and the decay time constant of mEPSCs in 25 of 27 lamina IIo neurons. Yohimbine (2 μM, an α2-adrenergic receptor antagonist), but not prazosin (2 μM, an α1-adrenergic receptor antagonist), blocked the inhibitory effect of clonidine on the mEPSCs. Clonidine (1–20 μM, n = 8) also significantly attenuated the peak amplitude of evoked EPSCs in a concentration-dependent manner. The effect of clonidine on evoked EPSCs was abolished in the presence of yohimbine ( n = 5). These data suggest that clonidine inhibits the excitatory synaptic input to lamina IIo neurons through activation of α2-adrenergic receptors located on the glutamatergic afferent terminals. Presynaptic inhibition of glutamate release from primary afferents onto lamina IIoneurons likely plays an important role in the analgesic action produced by activation of the descending noradrenergic system and α2-adrenergic agonists.

scholarly journals Impaired spike-gamma coupling of area CA3 fast-spiking interneurons as the earliest functional impairment in the AppNL-G-F mouse model of Alzheimer’s disease

2021 ◽  
Author(s):  
Luis Enrique Arroyo-García ◽  
Arturo G. Isla ◽  
Yuniesky Andrade-Talavera ◽  
Hugo Balleza-Tapia ◽  
Raúl Loera-Valencia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mouse Model ◽  
Functional Impairment ◽  
Amyloid Β ◽  
Gamma Oscillations ◽  
Gamma Oscillation ◽  
Gamma Rhythm ◽  
Fast Spiking

AbstractIn Alzheimer’s disease (AD) the accumulation of amyloid-β (Aβ) correlates with degradation of cognition-relevant gamma oscillations. The gamma rhythm relies on proper neuronal spike-gamma coupling, specifically of fast-spiking interneurons (FSN). Here we tested the hypothesis that decrease in gamma power and FSN synchrony precede amyloid plaque deposition and cognitive impairment in AppNL-G-F knock-in mice (AppNL-G-F). The aim of the study was to evaluate the amyloidogenic pathology progression in the novel AppNL-G-F mouse model using in vitro electrophysiological network analysis. Using patch clamp of FSNs and pyramidal cells (PCs) with simultaneous gamma oscillation recordings, we compared the activity of the hippocampal network of wild-type mice (WT) and the AppNL-G-F mice at four disease stages (1, 2, 4, and 6 months of age). We found a severe degradation of gamma oscillation power that is independent of, and precedes Aβ plaque formation, and the cognitive impairment reported previously in this animal model. The degradation correlates with increased Aβ1-42 concentration in the brain. Analysis on the cellular level showed an impaired spike-gamma coupling of FSN from 2 months of age that correlates with the degradation of gamma oscillations. From 6 months of age PC firing becomes desynchronized also, correlating with reports in the literature of robust Aβ plaque pathology and cognitive impairment in the AppNL-G-F mice. This study provides evidence that impaired FSN spike-gamma coupling is one of the earliest functional impairment caused by the amyloidogenic pathology progression likely is the main cause for the degradation of gamma oscillations and consequent cognitive impairment. Our data suggests that therapeutic approaches should be aimed at restoring normal FSN spike-gamma coupling and not just removal of Aβ.

PHASE DEPENDENT TRANSITION BETWEEN MULTISTABLE STATES IN A NEURAL NETWORK WITH RECIPROCAL INHIBITION

2004 ◽  
Vol 14 (05) ◽  
pp. 1559-1575 ◽  
Author(s):  
KATSUMI TATENO ◽  
HIDEYUKI TOMONARI ◽  
HATSUO HAYASHI ◽  
SATORU ISHIZUKA
Keyword(s):  
Neural Network ◽  
Network Model ◽  
Neural Network Model ◽  
Synaptic Input ◽  
Reciprocal Inhibition ◽  
Conduction Delay ◽  
Inhibitory Connection ◽  
Pacemaker Neurons ◽  
Excitatory Synaptic Input ◽  
Multistable State

We studied multistable oscillatory states of a small neural network model and switching of an oscillatory mode. In the present neural network model, two pacemaker neurons are reciprocally inhibited with conduction delay; one pacemaker neuron inhibits the other via an inhibitory nonpacemaker interneuron, and vice versa. The small network model shows bifurcations from quasi-periodic oscillation to chaos via period 3 with increase in the synaptic weight of the reciprocal inhibition. The route to chaos in the network model is different from that in the single pacemaker neuron. The network model exhibits several multistable states. In a regime of a weak inhibitory connection, in-phase beat, out-of-phase beat (period 3), and chaotic oscillation coexist at the multistable state. We can switch an oscillatory mode by an excitatory synaptic input to one of the pacemaker neurons through an afferent path. In a strong inhibitory connection regime, in-phase beat and out-of-phase beat (period 4) coexist at the multistable state. An excitatory synaptic input through the afferent path leads to the transition from the in-phase beat to the out-of-phase beat. The transition from the out-of-phase beat to the in-phase beat is induced by an inhibitory synaptic input via interneurons. A conduction delay, furthermore, causes the spontaneous transition from the in-phase beat to the out-of-phase beat. These transitions can be explained by phase response curves.

scholarly journals The principal neurons of the medial nucleus of the trapezoid body and NG2+ glial cells receive coordinated excitatory synaptic input

2009 ◽  
Vol 134 (2) ◽  
pp. 115-127 ◽  
Author(s):  
Jochen Müller ◽  
Daniel Reyes-Haro ◽  
Tatjyana Pivneva ◽  
Christiane Nolte ◽  
Roland Schaette ◽  
...  
Keyword(s):  
Glial Cell ◽  
Glial Cells ◽  
Synaptic Input ◽  
Medial Nucleus ◽  
Synaptic Structure ◽  
Excitatory Synaptic Input ◽  
Cell Processes ◽  
To Receive ◽  
Trapezoid Body ◽  
Axosomatic Synapse

Glial cell processes are part of the synaptic structure and sense spillover of transmitter, while some glial cells can even receive direct synaptic input. Here, we report that a defined type of glial cell in the medial nucleus of the trapezoid body (MNTB) receives excitatory glutamatergic synaptic input from the calyx of Held (CoH). This giant glutamatergic terminal forms an axosomatic synapse with a single principal neuron located in the MNTB. The NG2 glia, as postsynaptic principal neurons, establish synapse-like structures with the CoH terminal. In contrast to the principal neurons, which are known to receive excitatory as well as inhibitory inputs, the NG2 glia receive mostly, if not exclusively, α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor–mediated evoked and spontaneous synaptic input. Simultaneous recordings from neurons and NG2 glia indicate that they partially receive synchronized spontaneous input. This shows that an NG2+ glial cell and a postsynaptic neuron share presynaptic terminals.

scholarly journals Liraglutide modulates GABAergic signaling in rat hippocampal CA3 pyramidal neurons predominantly by presynaptic mechanism

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Omar Babateen ◽  
Sergiy V. Korol ◽  
Zhe Jin ◽  
Amol K. Bhandage ◽  
Aikeremu Ahemaiti ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Ca3 ◽  
Ca3 Pyramidal Neurons

Analysis of voltage-gated and synaptic conductances contributing to network excitability defects in the mutant mouse tottering

1994 ◽  
Vol 71 (1) ◽  
pp. 1-10 ◽  
Author(s):  
S. A. Helekar ◽  
J. L. Noebels
Keyword(s):  
Gabaa Receptor ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Channel Blockers ◽  
Gamma Aminobutyric Acid ◽  
Voltage Gated ◽  
Voltage Dependent ◽  
Prolonged Duration ◽  
Ca3 Pyramidal Neurons ◽  
The Difference

1. Intracellular current- and voltage-clamp recordings were carried out in CA3 pyramidal neurons from hippocampal slices of adult tg/tg mice and their coisogenic C57BL/6J (+/+) controls with the use of the single-electrode switch-clamp technique. The principal aim of this study was to investigate the mechanisms responsible for the tg gene-linked prolongation (mean 60%) of a giant synaptic response, the potassium-induced paroxysmal depolarizing shift (PDS) at depolarized membrane potentials (Vm -47 to -54 mV) during synchronous network bursting induced by 10 mM potassium ([K+]o). 2. To examine the role of intrinsic voltage-dependent conductances underlying the mutant PDS prolongation, neurons were voltage clamped by the use of microelectrodes filled with 100 mM QX-314 or QX-222 chloride (voltage-gated sodium channel blockers) and 2 M cesium sulphate (potassium channel blocker). The whole-cell currents active during the PDS showed a significantly prolonged duration (mean 34%) at depolarized Vms in tg/tg compared with +/+ cells, indicating that a defect in voltage-dependent conductances is unlikely to completely account for the mutant phenotype. 3. Bath application of 40 microM (DL)-2-aminophosphonovalerate (DL-APV) produced a 30% reduction in PDS duration in both genotypes but failed to significantly alter the tg gene-linked prolongation compared with the wild type. These data indicate that the mutant PDS abnormality does not result from a selective increase of the N-methyl-D-aspartate (NMDA) receptor-mediated excitatory synaptic component. 4. Blockade of gamma-aminobutyric acid-A (GABAA) transmission with picrotoxin (50 microM) or bicuculline (1–5 microM) completely eliminated the difference in PDS duration between the genotypes. Furthermore, although both GABAA receptor antagonists increased the mean PDS duration in +/+ neurons, they did not significantly alter it in tg/tg neurons. These findings are consistent with a reduction in GABAA receptor-mediated synaptic inhibition during bursting in the tg CA3 hippocampal network. 5. To test this hypothesis, bursting CA3 pyramidal neurons were loaded intracellularly with chloride by the use of KCl-filled microelectrodes to examine the effect of reversing the hyperpolarizing chloride-dependent GABAA receptor-mediated inhibitory postsynaptic component of the PDS. Chloride loading prolonged PDS duration in both genotypes, but the increase was greater in +/+ than in tg/tg neurons, indicating that a smaller GABAA inhibitory postsynaptic potential (IPSP) component was reversed in the mutant.(ABSTRACT TRUNCATED AT 400 WORDS)

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