Purinergic P2 receptors trigger adenosine release leading to adenosine A2A receptor activation and facilitation of long-term potentiation in rat hippocampal slices

Klann, Eric. Cell-permeable scavengers of superoxide prevent long-term potentiation in hippocampal area CA1. J. Neurophysiol. 80: 452–457, 1998. Long-term potentiation (LTP) in hippocampal area CA1 is generally dependent on N-methyl-d-aspartate (NMDA) receptor activation. Reactive oxygen species (ROS), including superoxide, are produced in response to NMDA receptor activation in a number of brain regions, including the hipppocampus. In this study, two cell-permeable manganese porphyrin compounds that mimic superoxide dismutase (SOD) were used to determine whether production of superoxide is required for the induction of LTP in area CA1 of rat hippocampal slices. Incubation of hippocampal slices with either Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) or Mn(III) tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP) prevented the induction of LTP. Incubation of slices with either light-inactivated MnTBAP or light-inactivated MnTMPyP had no effect on induction of LTP. Neither MnTBAP nor MnTMPyP was able to reverse preestablished LTP. These observations suggest that production of superoxide occurs in response to LTP-inducing stimulation and that superoxide is necessary for the induction of LTP.

Download Full-text

Homeostatic plasticity induced by brief activity deprivation enhances long-term potentiation in the mature rat hippocampus

Journal of Neurophysiology ◽

10.1152/jn.00058.2014 ◽

2014 ◽

Vol 112 (11) ◽

pp. 3012-3022 ◽

Cited By ~ 16

Author(s):

A. Félix-Oliveira ◽

R. B. Dias ◽

M. Colino-Oliveira ◽

D. M. Rombo ◽

A. M. Sebastião

Keyword(s):

Synaptic Transmission ◽

Hippocampal Slices ◽

Long Term Potentiation ◽

Receptor Activation ◽

Relative Strength ◽

Homeostatic Plasticity ◽

Hebbian Plasticity ◽

Term Potentiation ◽

Acute Hippocampal Slices

Different forms of plasticity occur concomitantly in the nervous system. Whereas homeostatic plasticity monitors and maintains neuronal activity within a functional range, Hebbian changes such as long-term potentiation (LTP) modify the relative strength of specific synapses after discrete changes in activity and are thought to provide the cellular basis for learning and memory. Here, we assessed whether homeostatic plasticity could influence subsequent LTP in acute hippocampal slices that had been briefly deprived of activity by blocking action potential generation and N-methyl-d-aspartate (NMDA) receptor activation for 3 h. Activity deprivation enhanced the frequency and the amplitude of spontaneous miniature excitatory postsynaptic currents and enhanced basal synaptic transmission in the absence of significant changes in intrinsic excitability. Changes in the threshold for Hebbian plasticity were evaluated by inducing LTP with stimulation protocols of increasing strength. We found that activity-deprived slices consistently showed higher LTP magnitude compared with control conditions even when using subthreshold theta-burst stimulation. Enhanced LTP in activity-deprived slices was also observed when picrotoxin was used to prevent the modulation of GABAergic transmission. Finally, we observed that consecutive LTP inductions attained a higher magnitude of facilitation in activity-deprived slices, suggesting that the homeostatic plasticity mechanisms triggered by a brief period of neuronal silencing can both lower the threshold and raise the ceiling for Hebbian modifications. We conclude that even brief periods of altered activity are able to shape subsequent synaptic transmission and Hebbian plasticity in fully developed hippocampal circuits.

Download Full-text

Caffeine-Mediated Presynaptic Long-Term Potentiation in Hippocampal CA1 Pyramidal Neurons

Journal of Neurophysiology ◽

10.1152/jn.00601.2002 ◽

2003 ◽

Vol 89 (6) ◽

pp. 3029-3038 ◽

Cited By ~ 63

Author(s):

Eduardo D. Martín ◽

Washington Buño

Keyword(s):

Nmda Receptors ◽

Glutamate Release ◽

Ryanodine Receptors ◽

Hippocampal Slices ◽

Long Term Potentiation ◽

Receptor Activation ◽

Cellular Mechanisms ◽

Pipette Solution ◽

Term Potentiation

We report a new form of long-term potentiation (LTP) in Schaffer collateral (SC)-CA1 pyramidal neuron synapses that originates presynaptically and does not require N-methyl-d-aspartate (NMDA) receptor activation nor increases in postsynaptic-free Ca2+. Using rat hippocampal slices, application of a brief “pulse” of caffeine in the bath evoked a nondecremental LTP (CAFLTP) of SC excitatory postsynaptic currents. An increased probability of transmitter release paralleled the CAFLTP, suggesting that it originated presynaptically. The P1 adenosine receptor antagonist 8-cyclopentyltheophylline and the P2 purinoreceptor antagonists suramin and piridoxal-5′-phosphate-azophenyl 2′,4′-disulphonate blocked the CAFLTP. Inhibition of Ca2+ release from caffeine/ryanodine stores by bath-applied ryanodine inhibited the CAFLTP, but ryanodine in the pipette solution was ineffective, suggesting a presynaptic effect of ryanodine. Previous induction of the “classical” LTP did not prevent the CAFLTP, suggesting that the LTP and the CAFLTP have different underlying cellular mechanisms. The CAFLTP is insensitive to the block of NMDA receptors by 2-amino-5-phosphonopentanoic acid and to Ca2+ chelation with intracellular 1,2-bis (2-aminophenoxy) ethane- N,N,N′ ,N′-tetraacetic acid, indicating that neither postsynaptic NMDA receptors nor increases in cytosolic-free Ca2+ participate in the CAFLTP. We conclude that the CAFLTP requires the interaction of caffeine with presynaptic P1, P2 purinoreceptors, and ryanodine receptors and is caused by an increased probability of glutamate release at SC terminals.

Download Full-text

Retrograde adenosine/A2A receptor signaling mediates presynaptic hippocampal LTP and facilitates epileptic seizures

10.1101/2021.10.07.463512 ◽

2021 ◽

Author(s):

Kaoutsar Nasrallah ◽

Coralie Berthoux ◽

Yuki Hashimotodani ◽

Andres E Chavez ◽

Michelle Gulfo ◽

...

Keyword(s):

Neurotransmitter Release ◽

Epileptic Seizures ◽

Long Term Potentiation ◽

Adenosine A2a Receptor ◽

Retrograde Signaling ◽

Mammalian Brain ◽

A2a Receptor ◽

Adenosine A2a

A long-term change in neurotransmitter release is a widely expressed mechanism controlling neural circuits in the mammalian brain. This presynaptic plasticity is commonly mediated by retrograde signaling whereby a messenger released from the postsynaptic neuron upon activity modifies neurotransmitter release in a long-term manner by targeting a presynaptic receptor. In the dentate gyrus (DG), the main input area of the hippocampus, granule cells (GCs) and mossy cells (MCs) form a recurrent excitatory circuit that is critically involved in DG function and epilepsy. Here, we identified adenosine/A2A receptor (A2AR) as a novel retrograde signaling system that mediates presynaptic long-term potentiation (LTP) at MC-GC synapses. Using an adenosine sensor, we found that neuronal activity triggered phasic, postsynaptic TrkB-dependent release of adenosine. Additionally, epileptic seizures released adenosine in vivo, while removing A2ARs from DG decreased seizure susceptibility. Thus, adenosine/A2AR retrograde signaling mediates presynaptic LTP that may contribute to DG-dependent learning and promote epilepsy.

Download Full-text