scholarly journals Tonic Activation of GABAB Receptors Reduces Release Probability at Inhibitory Connections in the Cerebellar Glomerulus

2009 ◽  
Vol 101 (6) ◽  
pp. 3089-3099 ◽  
Author(s):  
Lisa Mapelli ◽  
Paola Rossi ◽  
Thierry Nieus ◽  
Egidio D'Angelo
Keyword(s):  
Neurotransmitter Release ◽  
Mossy Fiber ◽  
Signal Transmission ◽  
Receptor Activation ◽  
Gabab Receptors ◽  
Dynamic Regulation ◽  
Release Probability ◽  
Receptor Modulation ◽  
Tonic Activation ◽  
Ambient Gaba

In the cerebellum, granule cells are inhibited by Golgi cells through GABAergic synapses generating complex responses involving both phasic neurotransmitter release and the establishment of ambient γ-aminobutyric acid (GABA) levels. Although at this synapse the mechanisms of postsynaptic integration have been clarified to a considerable extent, the mechanisms of neurotransmitter release remained largely unknown. Here we have investigated the quantal properties of release during repetitive neurotransmission, revealing that tonic GABAB receptor activation by ambient GABA regulates release probability. Blocking GABAB receptors with CGP55845 enhanced the first inhibitory postsynaptic current (IPSC) and short-term depression in a train while reducing trial-to-trial variability and failures. The changes caused by CGP55845 were similar to those caused by increasing extracellular Ca2+ concentration, in agreement with a presynaptic GABAB receptor modulation of release probability. However, the slow tail following IPSC peak demonstrated a remarkable temporal summation and was not modified by CGP55845 or extracellular Ca2+ increase. This result shows that tonic activation of presynaptic GABAB receptors by ambient GABA selectively regulates the onset of inhibition bearing potential consequences for the dynamic regulation of signal transmission through the mossy fiber–granule cell pathway of the cerebellum.

scholarly journals Presynaptic GABAB Receptors Regulate Retinohypothalamic Tract Synaptic Transmission by Inhibiting Voltage-Gated Ca2+ Channels

2006 ◽  
Vol 95 (6) ◽  
pp. 3727-3741 ◽  
Author(s):  
Mykhaylo G. Moldavan ◽  
Robert P. Irwin ◽  
Charles N. Allen
Keyword(s):  
Glutamate Release ◽  
Receptor Activation ◽  
Gabab Receptors ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Epsc Amplitude ◽  
Receptor Modulation ◽  
Joint Application ◽  
Retinohypothalamic Tract

Presynaptic GABAB receptor activation inhibits glutamate release from retinohypothalamic tract (RHT) terminals in the suprachiasmatic nucleus (SCN). Voltage-clamp whole cell recordings from rat SCN neurons and optical recordings of Ca2+-sensitive fluorescent probes within RHT terminals were used to examine GABAB-receptor modulation of RHT transmission. Baclofen inhibited evoked excitatory postsynaptic currents (EPSCs) in a concentration-dependent manner equally during the day and night. Blockers of N-, P/Q-, T-, and R-type voltage-dependent Ca2+ channels, but not L-type, reduced the EPSC amplitude by 66, 36, 32, and 18% of control, respectively. Joint application of multiple Ca2+ channel blockers inhibited the EPSCs less than that predicted, consistent with a model in which multiple Ca2+ channels overlap in the regulation of transmitter release. Presynaptic inhibition of EPSCs by baclofen was occluded by ω-conotoxin GVIA (≤72%), mibefradil (≤52%), and ω-agatoxin TK (≤15%), but not by SNX-482 or nimodipine. Baclofen reduced both evoked presynaptic Ca2+ influx and resting Ca2+ concentration in RHT terminals. Tertiapin did not alter the evoked EPSC and baclofen-induced inhibition, indicating that baclofen does not inhibit glutamate release by activation of Kir3 channels. Neither Ba2+ nor high extracellular K+ modified the baclofen-induced inhibition. 4-Aminopyridine (4-AP) significantly increased the EPSC amplitude and the charge transfer, and dramatically reduced the baclofen effect. These data indicate that baclofen inhibits glutamate release from RHT terminals by blocking N-, T-, and P/Q-type Ca2+ channels, and possibly by activation of 4-AP–sensitive K+ channels, but not by inhibition of R- and L-type Ca2+ channels or by Kir3 channel activation.

LTP Regulates Burst Initiation and Frequency at Mossy Fiber–Granule Cell Synapses of Rat Cerebellum: Experimental Observations and Theoretical Predictions

2006 ◽  
Vol 95 (2) ◽  
pp. 686-699 ◽  
Author(s):  
Thierry Nieus ◽  
Elisabetta Sola ◽  
Jonathan Mapelli ◽  
Elena Saftenku ◽  
Paola Rossi ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Granule Cell ◽  
Mossy Fiber ◽  
Gain Control ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Excitatory Postsynaptic Potential ◽  
Release Probability ◽  
Whole Cell Patch Clamp ◽  
Nmda Current

Long-term potentiation (LTP) is a synaptic change supposed to provide the cellular basis for learning and memory in brain neuronal circuits. Although specific LTP expression mechanisms could be critical to determine the dynamics of repetitive neurotransmission, this important issue remained largely unexplored. In this paper, we have performed whole cell patch-clamp recordings of mossy fiber–granule cell LTP in acute rat cerebellar slices and studied its computational implications with a mathematical model. During LTP, stimulation with short impulse trains at 100 Hz revealed earlier initiation of granule cell spike bursts and a smaller nonsignificant spike frequency increase. In voltage-clamp recordings, short AMPA excitatory postsynaptic current (EPSC) trains showed short-term facilitation and depression and a sustained component probably generated by spillover. During LTP, facilitation disappeared, depression accelerated, and the sustained current increased. The N-methyl-d-aspartate (NMDA) current also increased. In agreement with a presynaptic expression caused by increased release probability, similar changes were observed by raising extracellular [Ca2+]. A mathematical model of mossy fiber–granule cell neurotransmission showed that increasing release probability efficiently modulated the first-spike delay. Glutamate spillover, by causing tonic NMDA and AMPA receptor activation, accelerated excitatory postsynaptic potential (EPSP) temporal summation and maintained a sustained spike discharge. The effect of increasing neurotransmitter release could not be replicated by increasing receptor conductance, which, like postsynaptic manipulations enhancing intrinsic excitability, proved very effective in raising granule cell output frequency. Independent regulation of spike burst initiation and frequency during LTP may provide mechanisms for temporal recoding and gain control of afferent signals at the input stage of cerebellar cortex.

scholarly journals 5-HT1A, 5-HT2, and GABAB receptors interact to modulate neurotransmitter release probability in layer 2/3 somatosensory rat cortex as evaluated by the paired pulse protocol

2005 ◽  
Vol 82 (6) ◽  
pp. 890-890
Author(s):  
José L. Torres-Escalante ◽  
Jaime A. Barral ◽  
María D. Ibarra-Villa ◽  
Azucena Pérez-Burgos ◽  
José L. Góngora-Alfaro ◽  
...  
Keyword(s):  
Neurotransmitter Release ◽  
Gabab Receptors ◽  
Paired Pulse ◽  
Rat Cortex ◽  
Release Probability ◽  
Layer 2

scholarly journals Neurexins regulate presynaptic GABAB-receptors at central synapses

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Fujun Luo ◽  
Alessandra Sclip ◽  
Sean Merrill ◽  
Thomas C. Südhof
Keyword(s):  
Active Zone ◽  
Neurotransmitter Release ◽  
Molecular Mechanisms ◽  
Pyramidal Neurons ◽  
Receptor Activation ◽  
Gabab Receptors ◽  
Inhibitory Synapses ◽  
Receptor Signaling ◽  
Ca1 Region ◽  
Presynaptic Active Zone

AbstractDiverse signaling complexes are precisely assembled at the presynaptic active zone for dynamic modulation of synaptic transmission and synaptic plasticity. Presynaptic GABAB-receptors nucleate critical signaling complexes regulating neurotransmitter release at most synapses. However, the molecular mechanisms underlying assembly of GABAB-receptor signaling complexes remain unclear. Here we show that neurexins are required for the localization and function of presynaptic GABAB-receptor signaling complexes. At four model synapses, excitatory calyx of Held synapses in the brainstem, excitatory and inhibitory synapses on hippocampal CA1-region pyramidal neurons, and inhibitory basket cell synapses in the cerebellum, deletion of neurexins rendered neurotransmitter release significantly less sensitive to GABAB-receptor activation. Moreover, deletion of neurexins caused a loss of GABAB-receptors from the presynaptic active zone of the calyx synapse. These findings extend the role of neurexins at the presynaptic active zone to enabling GABAB-receptor signaling, supporting the notion that neurexins function as central organizers of active zone signaling complexes.

Adenosine Receptor Modulation of Hypoxic-ischemic Injury in Striatum of Newborn Piglets

2020 ◽  
Vol 17 (4) ◽  
pp. 510-517
Author(s):  
Santiago Ortega-Gutierrez ◽  
Brandy Jones ◽  
Alan Mendez-Ruiz ◽  
Pankhil Shah ◽  
Michel T. Torbey
Keyword(s):  
Oxidative Stress ◽  
Atpase Activity ◽  
Neuronal Injury ◽  
Receptor Activation ◽  
Adult Mortality ◽  
Vehicle Group ◽  
Sodium Potassium ◽  
Receptor Modulation ◽  
A2a Receptor ◽  
Potassium Atpase

Background: Hypoxic-ischemic encephalopathy (HIE) is a major cause of pediatric and adult mortality and morbidity. Unfortunately, to date, no effective treatment has been identified. In the striatum, neuronal injury is analogous to the cellular mechanism of necrosis observed during NMethyl- D-Aspartate (NMDA) excitotoxicity. Adenosine acts as a neuromodulator in the central nervous system, the role of which relies mostly on controlling excitatory glutamatergic synapses. Objective: To examine the effect of pretreatment of SCH58261, an adenosine 2A (A2A) receptor antagonist and modulator of NMDA receptor function, following hypoxic-ischemia (HI) on sodium- potassium ATPase (Na+, K+-ATPase) activity and oxidative stress. Methods: Piglets (4-7 days old) were subjected to 30 min hypoxia and 7 min of airway occlusion producing asphyxic cardiac arrest. Groups were divided into four categories: HI samples were divided into HI-vehicle group (n = 5) and HI-A2A group (n = 5). Sham controls were divided into Sham vehicle (n = 5) and Sham A2A (n = 5) groups. Vehicle groups were pretreated with 0.9% saline, whereas A2A animals were pretreated with SCH58261 10 min prior to intervention. Striatum samples were collected 3 h post-arrest. Sodium-potassium ATPase (Na+, K+-ATPase) activity, malondialdehyde (MDA) + 4-hydroxyalkenals (4-HDA) and glutathione (GSH) levels were compared. Results: Pretreatment with SCH58261 significantly attenuated the decrease in Na+, K+-ATPase, decreased MDA+4-HDA levels and increased GSH in the HI-A2A group when compared to HIvehicle. Conclusion: A2A receptor activation may contribute to neuronal injury in newborn striatum after HI in association with decreased Na+, K+-ATPase activity and increased oxidative stress.

How Synaptic Release Probability Shapes Neuronal Transmission: Information-Theoretic Analysis in a Cerebellar Granule Cell

2010 ◽  
Vol 22 (8) ◽  
pp. 2031-2058 ◽  
Author(s):  
Angelo Arleo ◽  
Thierry Nieus ◽  
Michele Bezzi ◽  
Anna D'Errico ◽  
Egidio D'Angelo ◽  
...  
Keyword(s):  
Information Transmission ◽  
Numerical Simulations ◽  
Granule Cell ◽  
Mossy Fiber ◽  
Dendritic Tree ◽  
Long Term Potentiation ◽  
Cerebellar Granule Cell ◽  
Information Theoretic ◽  
Cerebellar Granule ◽  
Release Probability

A nerve cell receives multiple inputs from upstream neurons by way of its synapses. Neuron processing functions are thus influenced by changes in the biophysical properties of the synapse, such as long-term potentiation (LTP) or depression (LTD). This observation has opened new perspectives on the biophysical basis of learning and memory, but its quantitative impact on the information transmission of a neuron remains partially elucidated. One major obstacle is the high dimensionality of the neuronal input-output space, which makes it unfeasible to perform a thorough computational analysis of a neuron with multiple synaptic inputs. In this work, information theory was employed to characterize the information transmission of a cerebellar granule cell over a region of its excitatory input space following synaptic changes. Granule cells have a small dendritic tree (on average, they receive only four mossy fiber afferents), which greatly bounds the input combinatorial space, reducing the complexity of information-theoretic calculations. Numerical simulations and LTP experiments quantified how changes in neurotransmitter release probability (p) modulated information transmission of a cerebellar granule cell. Numerical simulations showed that p shaped the neurotransmission landscape in unexpected ways. As p increased, the optimality of the information transmission of most stimuli did not increase strictly monotonically; instead it reached a plateau at intermediate p levels. Furthermore, our results showed that the spatiotemporal characteristics of the inputs determine the effect of p on neurotransmission, thus permitting the selection of distinctive preferred stimuli for different p values. These selective mechanisms may have important consequences on the encoding of cerebellar mossy fiber inputs and the plasticity and computation at the next circuit stage, including the parallel fiber–Purkinje cell synapses.

GABAA receptor activation and open-channel block by volatile anaesthetics: a new principle of receptor modulation?

2002 ◽  
Vol 451 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Rainer Haseneder ◽  
Gerhard Rammes ◽  
Walter Zieglgänsberger ◽  
Eberhard Kochs ◽  
Gerhard Hapfelmeier
Keyword(s):  
Gabaa Receptor ◽  
Open Channel ◽  
Receptor Activation ◽  
Channel Block ◽  
Volatile Anaesthetics ◽  
Open Channel Block ◽  
Receptor Modulation

Inhibition of transient potassium current in cultured and acutely dissociated mouse hippocampal neurons by GABAA receptor activation

1996 ◽  
Vol 76 (2) ◽  
pp. 816-824
Author(s):  
R. L. Wu ◽  
M. E. Barish
Keyword(s):  
Mouse Brain ◽  
Hippocampal Neurons ◽  
Potassium Current ◽  
Receptor Activation ◽  
Gabab Receptors ◽  
Cell Swelling ◽  
Cultured Neurons ◽  
Embryonic Mouse ◽  
Voltage Gated ◽  
A Current

1. The regulation of A-current, one of several transient voltage-gated potassium currents, was studied using whole cell gigaohm seal voltage-clamp techniques on hippocampal pyramidal neurons that were either acutely dissociated from postnatal mouse brain or isolated from embryonic mouse brain and grown in dissociated culture. These neurons also express gamma-aminobutyric acid-A (GABAA) receptors, the activation of which can, under some circumstances, depolarize immature neurons and the dendrites of more mature neurons. 2. Application of GABA (50 microM) reduced the amplitude of A-current when potassium current amplitude was measured during a period of slow and incomplete desensitization of IGABA. A-current was reduced to 67 +/- 9% of control (mean +/- SD, n - 14) in acutely dissociated neurons, and to 64 +/- 11% of control (n = 15) in cultured neurons. Similar A-current reductions were seen in large outside-out membrane patches pulled from somata of cultured neurons, an observation suggesting that imperfect control of membrane voltage was not responsible for A-current inhibition. 3. A-current inhibition exhibited the sensitivity expected of a GABAA-sensitive process. It was mimicked by muscimol and blocked by bicuculline, picrotoxin, and reduction of [Cl-] in the external solution. Baclophen and phaclophen, effective as agonist and antagonist on GABAB receptors, did not affect A-currents or their inhibition. Reduction in extracellular osmolarity (to increase cell swelling as might occur with Cl- entry), or removal of external HCO3- (which might flow inward through GABAA channels and cause local external acidification), did not affect A-current or its inhibition. The mechanisms of inhibition is not clear at present. 4. We suggest that reduced A-current may favor GABA-induced depolarization and consequent activation of voltage-gated calcium channels.

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