Long-term potentiation of synaptic transmission in the hippocampus is the primary experimental model for investigating the synaptic basis of learning and memory in vertebrates. The best understood form of long-term potentiation is induced by the activation of the N-methyl-D-aspartate receptor complex. This subtype of glutamate receptor endows long-term potentiation with Hebbian characteristics, and allows electrical events at the postsynaptic membrane to be transduced into chemical signals which, in turn, are thought to activate both pre- and postsynaptic mechanisms to generate a persistent increase in synaptic strength.

A synaptic model of memory: long-term potentiation in the hippocampus

The distinct protein aggregates that are found in Alzheimer's, Parkinson's, Huntington's and prion diseases seem to cause these disorders. Small intermediates - soluble oligomers - in the aggregation process can confer synaptic dysfunction, whereas large, insoluble deposits might function as reservoirs of the bioactive oligomers. These emerging concepts are exemplified by Alzheimer's disease, in which amyloid beta-protein oligomers adversely affect synaptic structure and plasticity. Findings in other neurodegenerative diseases indicate that a broadly similar process of neuronal dysfunction is induced by diffusible oligomers of misfolded proteins.

Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide.

### A. Overview

Extracellular purines (adenosine, ADP, and ATP) and pyrimidines (UDP and UTP) are important signaling molecules that mediate diverse biological effects via cell-surface receptors termed purine receptors. In this review particular emphasis is placed on the discrepancy between the

/pdf/receptors-for-purines-and-pyrimidines-56f78tnpew.pdf

Receptors for Purines and Pyrimidines

The ionotropic glutamate receptors are ligand-gated ion channels that mediate the vast majority of excitatory neurotransmission in the brain. The cloning of cDNAs encoding glutamate receptor subunits, which occurred mainly between 1989 and 1992 ([Hollmann and Heinemann, 1994][1]), stimulated this

/pdf/the-glutamate-receptor-ion-channels-560mntczdb.pdf

The glutamate receptor ion channels

LTP and LTD: an embarrassment of riches.

La stimulation des fibres afferentes non nociceptives est largement utilisee en clinique pour le traitement de la douleur, mais on ne connait toujours pas les mecanismes qui en sont responsables. Nous presentons ici des resultats d'etudes electrophysiologiques in vivo, chez l'animal, suggerant l'implication des purines dans la mediation chimique de l'inhibition des neurones nociceptifs de la corne dorsale en reponse a l'application d'une vibration cutanee peripherique. Ce mecanisme purinergique pourrait representer le substrat neuronal de l'analgesie observee chez l'humain a l'aide de traitements a la vibration, ce qui permet d'envisager des strategies pour l'amelioration de l'efficacite de ce type de traitement.

Le Rôle des purines dans la modulation de la douleur au niveau spinal par la stimulation d'afférences non nociceptives

Loss of inhibition in a circuit in the primary somatosensory cortex that controls the activity of layer 5 neurons drives pain hypersensitivity. Restoring this inhibition resets the inhibitory–excitatory balance, producing analgesia.

VIP cortical conductors set the tone for chronic pain

A number of lines of evidence support roles for adenosine and adenosine 5'-triphosphate (ATP) in the transmission and modulation of somatosensory information in the dorsal horn of the spinal cord. Adenosine and ATP have also been demonstrated to have nociceptive (pain-related) and antinociceptive actions in the periphery. Thus, adenosine and ATP have multiple functions in somatosensory processing, which are dependent upon the site and on the relative activation of P1 and P2 purinoceptor subtypes on neurons and non-neuronal cells. The multiple roles provide a rich number of potential therapeutic targets for producing analgesia in a number of clinical pain states. However, because of the multiple and potentially contrasting pro- and anti-nociceptive roles of adenosine and ATP, pharmacological targeting of specific sites and purinoceptor subtypes will be necessary to achieve maximum effectiveness while minimizing side effects.

Multiple roles of ATP and adenosine in somatosensory processing: Therapeutic implications

https://doi.org/10.1016/j.epsl.2022.117408

Michael W. Salter

Papers

Le Rôle des purines dans la modulation de la douleur au niveau spinal par la stimulation d'afférences non nociceptives

VIP cortical conductors set the tone for chronic pain

Multiple roles of ATP and adenosine in somatosensory processing: Therapeutic implications

Hydrous silicate melts and the deep mantle H2O cycle

A Straightjacket for Pain