Excitatory synapse

Glutamate is a small amino acid which constitutes the most important neurotransmitter at excitatory synapses in the mammalian brain. Glutamate can act on several different types of receptors including cation channels and G-protein-coupled receptors. 

In a classical neural pathway, such as that depicted in Fig. 1.3, neuron A must excite neuron B and at the same time inhibit neuron C in order to optimise the excitation of B. It could achieve this with one NT able to activate receptors linked to different events on B and C. Of course, neuron C would have other inputs, some of which would be excitatory and if the same NT was used it could activate the inhibitory mechanism on C as well. Also, the NT released from A might be able to stimulate as well as inhibit neuron C (Fig. 1.3(a)). Even the provision of separate receptors linked to excitation and inhibition would not overcome these problems since both would be accessible to the NT. One possible solution, used in the CNS, is to restrict the NT to the synapse at which it is released by structural barriers or rapid degradation. Also the inputs and receptors linked to excitation could be separated anatomically from those linked to inhibition and, in fact, there is electrophysiological and morphological evidence that excitatory synapses are mainly on dendrites and inhibitory ones on the soma of large neurons (Fig. 1.3(b)). Nevertheless, the problem of overlap would be eased if two NTs were released, one to activate only those receptors linked to excitation and another to evoke just inhibition, i.e. place the determinant of function partly back on the NT (Fig. 1.3(c)). This raises a different problem which has received much consideration. Can a neuron release more than one NT ... 

Figure 3.1 Schematic representation of a generic excitatory synapse in the brain. The presynaptic terminal releases the transmitter glutamate by fusion of transmitter vesicles with the nerve terminal membrane. Glutamate diffuses rapidly across the synaptic cleft to bind to and activate AMPA and NMDA receptors. In addition, glutamate may bind to metabotropic G-protein-coupled glutamate receptors located perisynaptically to cause initiation of intracellular signalling via the G-protein, Gq, to activate the enzyme phospholipase and hence produce inositol triphosphate (IP3) which can release Ca from intracellular calcium stores...

Kreitzer AC, Regehr WG. Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells. Neuron 2001 29 717-727. 

Compare and contrast excitatory synapses and inhibitory synapses... 

Wang, H., Pineda, V. V., Chan, G. C. K., Wong, S. T., Muglia, L. J. and Storm, D. R. Type 8 adenylyl cyclase is targeted to excitatory synapses and required for mossy fiber long-term potentiation. /. Neurosci. 23 9710-9718, 2003. 

These findings were confirmed and extended by in vitro electrophysiological studies of slices from normal animals that revealed that subtle (e.g. 20%) reductions of inhibitory synaptic function could lead to epileptiform activity. Importantly, activation of excitatory synapses is often pivotal in the expression of a seizure in distinct models in vitro. In addition to these important pharmacological observations, electrophysiological analyses of individual neurons during a partial seizure revealed that neurons undergo a massive depolarization and fire action potentials at high frequencies (Fig. 37-1) [3], This pattern of... 

GABAergic inhibition between interneurones can also be enhanced by glutamate spillover from neighboring excitatory synapses acting on kainate receptors (38). In CA1 interneurones, an increase in spontaneous action potential discharge and consequent increase in spontaneous IPSC frequency is observed to kainate and ATPA application (34,36,46,63,83,96,98,103). These effects are in part owing to direct depolarization of... 

High-frequency activation of excitatory synapses produces a long-lasting increase in synaptic efficacy, and excitatory stimuli with low frequency are unfavorable for the growth of synaptic efficiency. 

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). 

Bredt DS, Nicoll RA AMPA receptor trafficking at excitatory synapses. Neuron 2003 40 361. [PMID 14556714]... 

Opioid receptors are not only located at excitatory synapses, but are also expressed at inhibitory neurons. At these synapses, opioids inhibit the transmission of the... 

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