Synapse plasticity

Conversely, a new line of inquiry examined glutamatergic activity, not as a blocker of neurotransmission but as an agonist of AMPA type receptors. A new class of compounds, called ampakines, act as long-term boosters of the learning process, Aniracetam [206] is considered as the major product in this series. It improves performance in all classical behavioural tests in animal models. The question which has to be answered is whether these compounds simply have symptomatic effects on memory processes or whether they have complementary properties such as inhibition of cell death [207], Furthermore, certain compounds currently classed as ampakines such as oxiracetam and piracetam have not been shown to be effective in Alzheimer s disease. Others, such as nefiracetam (12) are in the animal experimentation stage and appear to be promising because of their impact on the neuronal cell adhesion molecules (NCAM) [208] and their effect on synapse plasticity. 

ChEs control the duration of ACh-mediated action on post-synaptic receptors in cholinergic synapses, and have non-hydrolytic roles in nervous systems development and plasticity. 

Subunit changes are other mechanisms that alter the physiology of GABA synapses and account for plastic changes seen following chronic ethanol treatment. 

Long-term potentiation (LTP) is a synaptic plasticity phenomenon that corresponds to an increase in the synaptic strength (increase in the post-synaptic response observed for the same stimulation of the presynaptic terminals) observed after a high frequency stimulation (tetanus) of the afferent fibres. This increased response is still observed hours and even days after the tetanus. The phenomenon is often observed at glutamatergic synapses and involves, in most cases, the activation of the V-methyl D-aspartate (NMDA) subtype of ionotropic glutamate receptors. 

Ichikawa M., Matsuoka M. and Mori K. (1995). Plastic effects of soiled bedding on the structure of synapses in rat accessory olfactory bulb. Synapse 21, 104-109. 

M. Ash and I. Ash, Handbook of Industrial Chemical Additives, Synapse Information Resources, Endicott, NY (2000). G. Pritchard, Plastics Additives. An A-Z Reference, Chapman Hall, London (1998). 

Long-term potentiation and depression of glutamatergic synapses are involved in many models for brain function and development. A key factor in the plasticity is a change in the AMPA and kainate... 

We utilized this technique to analyze Scrapper gene-dehcient (SCR-KO) mice.21 SCRAPPER, a protein that we have recently reported, is localized at synapses in neurons. It is a ubiquitin E3 ligase that is involved in the decomposition of RIM (Rab3-interacting molecule) 1, an important regulator of synaptic plasticity, and thus regulates synaptic transmissions.22... 

Fritschy, J.-M. and Brunig, I. Formation and plasticity of GABAergic synapses physiological mechanisms and pathophysiological implications. Pharmacol. Ther. 98 299-323, 2003. 

Curtis, J. and Finkbeiner, S. Sending signals from the synapse to the nucleus possible roles for CaMK, Ras/ERK, and SAPK pathways in the regulation of synaptic plasticity and neuronal growth. /. Neurosci. Res. 58 88-95,1999. 

Tyrosine phosphorylation plays an important role in synaptic transmission and plasticity. Evidence for this role is that modulators of PTKs and PTPs have been shown to be intimately involved in these synaptic functions. Among the various modulators of PTKs, neuro-trophins have been extensively studied in this regard and will be our focus in the following discussion (for details of growth factors, see Ch. 27). BDNF and NT-3 have been shown to potentiate both the spontaneous miniature synaptic response and evoked synaptic transmission in Xenopus nerve-muscle cocultures. Neurotrophins have also been reported to augment excitatory synaptic transmission in central synapses. These effects of neurotrophins in the neuromuscular and central synapses are dependent on tyrosine kinase activities since they are inhibited by a tyrosine kinase inhibitor, K-252a. Many effects of neurotrophins on synaptic functions have been attributed to the enhancement of neurotransmitter release BDNF-induced increase in neurotransmitter release is a result of induced elevation in presynaptic cytosolic calcium. Accordingly, a presynaptic calcium-depen-dent phenomenon - paired pulse facilitation - is impaired in mice deficient in BDNF. 

Robust decreases in the expression of the various proteasome subunits and ubiquitin-conjugating enzymes have been described in prefrontal cortex in schizophrenia. Neuronal ubiquitin and proteasomes play an important role in the assembly, function and plasticity of the synapse. Structural proteins including tubulin and a-spectrin also show decreased expression in prefrontal cortex. 

The recently developed GLUK5 selective compound LY382884 (47) is the first antagonist that is selective enough for kainate receptors over AMPA receptors to be used to study the functions of native KA receptors in the presence of intact AMPA receptor-mediated transmission. The use of LY382884 has uncovered a role for kainate receptors in the regulation of short- and long-term synaptic plasticity in the mossy-fiber pathway (49,77) as well as at thalamocortical synapses (87) (Fig. 3)... 

Contractor, A., Swanson, G., and Heinemann, S. F. (2001) Kainate receptors are involved in short- and long-term plasticity at mossy fiber synapses in the hippocampus. Neuron 29, 209-216. 

Kamiya, H Ozawa, S and Manabe, T. (2002) Kainate receptor-dependent short-term plasticity of presynaptic Ca2 influx at the hippocampal mossy hber synapses../. Neurosci. 22(21), 9237-9243. 

The response of the brain to both acute and chronic stress can be discussed in terms of its capacity to demonstrate its dynamic plasticity. The term plasticity describes almost any change in the brain, from the chemical level to the formation of new neurons and synapses. Prolonged or chronic stress has specific effects on the structure and function of the synapses in different brain regions. The neurons in different regions may show signs of atrophy, cell death, as a result of chronic psychosocial stress, as well as after... 

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