Neurotransmission

About: Neurotransmission is a research topic. Over the lifetime, 19641 publications have been published within this topic receiving 1185107 citations.

Alzheimer's Disease Is a Synaptic Failure

Abstract: In its earliest clinical phase, Alzheimer's disease characteristically produces a remarkably pure impairment of memory. Mounting evidence suggests that this syndrome begins with subtle alterations of hippocampal synaptic efficacy prior to frank neuronal degeneration, and that the synaptic dysfunction is caused by diffusible oligomeric assemblies of the amyloid β protein.

Selective impairment of learning and blockade of long-term potentiation by an N -methyl-D-aspartate receptor antagonist, AP5

Abstract: Recent work has shown that the hippocampus contains a class of receptors for the excitatory amino acid glutamate that are activated by N-methyl-D-aspartate (NMDA) and that exhibit a peculiar dependency on membrane voltage in becoming active only on depolarization. Blockade of these sites with the drug aminophosphonovaleric acid (AP5) does not detectably affect synaptic transmission in the hippocampus, but prevents the induction of hippocampal long-term potentiation (LTP) following brief high-frequency stimulation. We now report that chronic intraventricular infusion of D,L-AP5 causes a selective impairment of place learning, which is highly sensitive to hippocampal damage, without affecting visual discrimination learning, which is not. The L-isomer of AP5 did not produce behavioural effects. AP5 treatment also suppressed LTP in vivo. These results suggest that NMDA receptors are involved in spatial learning, and add support to the hypothesis that LTP is involved in some, but not all, forms of learning.

Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones.

Abstract: Acidic amino acids are putative excitatory synaptic transmitters1,2, the ionic mechanism of which is not well understood. Recent studies with selective agonists and antagonists suggest that neurones of the mammalian central nervous system possess several different receptors for acidic amino acids3,4, which in turn are coupled to separate conductance mechanisms5. N-methyl-D-aspartic acid (NMDA) is a selective agonist for one of these receptors3,4. The excitatory action of amino acids acting at NMDA receptors is remarkably sensitive to the membrane potential and it has been suggested that the NMDA receptor is coupled to a voltage-sensitive conductance6–9. Recently, patch-clamp experiments have shown the voltage-dependent block by Mg2+ of current flow through ion channels activated by L-glutamate10. We now show using voltage-clamp experiments on mouse spinal cord neurones that the voltage-sensitivity of NMDA action is greatly reduced on the withdrawal of physiological concentrations (∼1 mM) of Mg2+ from the extracellular fluid. This provides further evidence that Mg2+ blocks inward current flow through ion channels linked to NMDA receptors.

Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins

Abstract: In neural systems, information is often carried by ensembles of cells rather than by individual units. Optical indicators provide a powerful means to reveal such distributed activity, particularly when protein-based and encodable in DNA: encodable probes can be introduced into cells, tissues, or transgenic organisms by genetic manipulation, selectively expressed in anatomically or functionally defined groups of cells, and, ideally, recorded in situ, without a requirement for exogenous cofactors. Here we describe sensors for secretion and neurotransmission that fulfil these criteria. We have developed pH-sensitive mutants of green fluorescent protein ('pHluorins') by structure-directed combinatorial mutagenesis, with the aim of exploiting the acidic pH inside secretory vesicles to monitor vesicle exocytosis and recycling. When linked to a vesicle membrane protein, pHluorins were sorted to secretory and synaptic vesicles and reported transmission at individual synaptic boutons, as well as secretion and fusion pore 'flicker' of single secretory granules.

Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus.

Abstract: 1. The effects of excitatory amino acids and some antagonists applied by ionophoresis to stratum radiatum in the CA1 region of rat hippocampal slices were examined on the locally recorded field e.p.s.p. evoked by stimulation of the Schaffer collateral-commissural projection. 2. L-glutamate, L-aspartate and the more potent and selective excitatory amino acids quisqualate, kainate and N-methyl-DL-aspartate (NMA) depressed the e.p.s.p., presumably through depolarization and/or a change in membrane conductance. 3. The depression induced by kainate considerably outlasted the period of ejection whereas NMA depressions were rapidly reversible and were often followed by a potentiation of the e.p.s.p. In higher doses NMA also depressed the presynaptic fibre volley. The possible involvement of these effects in neurotoxicity and synaptic plasticity is raised. 4. The selective NMA antagonist, DL-2-amino-5-phosphonovalerate (APV) applied in doses which abolished responses to NMA, had no effect on the e.p.s.p. but prevented long term potentiation (l.t.p.) of synaptic transmission evoked by high frequency stimulation of the Schaffer collateral-commissural pathway. Other antagonists which had little or no effect on normal synaptic transmission included D-alpha-aminoadipate (DAA), the optical isomers of 2-amino-4-phosphonobutyrate (APB) and L-glutamate diethylester (GDEE). 5. In contrast, gamma-D-glutamylglycine (DGG), applied in amounts which affected quisqualate and kainate actions as well as those of NMA, was an effective synaptic antagonist whilst having no effect on the presynaptic fibre volley. 6. These results indicate that the synaptic receptor in the Schaffer collateral-commissural pathway may be of the kainate or quisqualate type. Although NMA receptors do not appear to be involved in normal synaptic transmission in this pathway they may play a role in synaptic plasticity. The interaction of L-glutamate and L-aspartate with these receptors is discussed.