Glutamatergic synapses

Altered synaptic properties Numerous changes in the properties of inhibitory (GABAergic) and excitatory (glutamatergic) synapses have been reported. While the simple adage of an imbalance between inhibitory and excitatory neurotransmission in epilepsy is not generally applicable, some forms of inhibition are lost or impaired in epilepsy. Likewise, an increased function of glutamate receptors has been demonstrated in some brain areas. 

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. 

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... 

Lehre, K. P. and Danbolt, N. C. The number of glutamate transporter subtype molecules at glutamatergic synapses chemical and stereological quantification in young adult rat brain. /. Neurosci. 18 8751-8757,1998. 

LONG-TERM POTENTIATION OR DEPRESSION OF GLUTAMATERGIC SYNAPSES MAY UNDERLIE LEARNING 271... 

NMDA and AMPA receptors are spread across the post-synaptic density (PSD), whereas metabotropic glutamate receptors (except mGluR7) are located along the periphery of the PSD (Fig. 15-2). NMDA receptors appear to be present at most or all glutamatergic synapses whereas the content of AMPA receptors is variable - from zero to about 50 receptors per PSD [33]. Some synapses are silent , meaning that activation of them does not elicit AMPA receptor currents when the plasma membrane is hyperpolarized and Mg2+ blocks NMDA receptors. Such silent synapses contain only NMDA receptors. However, AMPA receptors are recruited from the cytosol to the PSD to activate such silent synapses in LTP. 

Strengthening of glutamatergic synapses within the VTA is also observed in response to other abused drugs such as cocaine and amphetamine. Importantly, this cannot be induced by non-addictive drugs such as fluoxetine or carbamazepine (Saal et al. 2003). Hence, synaptic neuroadaptation at excitatory synapses is an important key step in the development of addiction (Kauer and Malenka 2007). 

FIGURE 2.3 Glutamatergic synapse. Glutamate binds to ionotropic receptors (1) and metabotropic receptors (2). The glutamate transporter (3) pumps glutamate back into the glutamatergic neuron. 

Vidal C Nicotinic potentiation of glutamatergic synapses in the prefrontal cortex new insight into the analysis of the role of nicotinic receptors in cognitive functions. Drug Dev Res 31 120-126, 1994b... 

Rimonabant CBi receptor agonist Decreases neurotransmitter release at GABAergic and glutamatergic synapses Approved in USA and Europe to treat obesity Smoking cessation is an off-label indication Major depression, including increased risk of suicide... 

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