Receptor excitatory

Figure 1.3 Some possible basic neurotransmitter-synaptic arrangements for the excitation and inhibition of different neurons, (a) The single NT activates neuron B and inhibits neuron C by being able to activate both excitatory and inhibitory receptors or, more probably, acting on one receptor linked to both events. There is potential, however, for the NT to activate any inhibitory receptors that may be on B or excitatory receptors on C. (b) The same NT is used as in (a) but the excitatory receptors are now only on dendrites and separated from the inhibitory receptors only on the soma. There is less chance of unwanted mixed effects, (c) Neuron A releases distinct excitatory and inhibitory NTs from its two terminals each acting on specific and morphologically separated receptors. But this depends on a neuron being able to release two NTs. (d) Neuron A releases the same NT from both terminals. It directly excites B but inhibits C through activating an inhibitory interneuron (I) which releases an inhibitory NT onto specific receptors on C. This last scheme (d) is clearly more functional and is widely used...

Critical periods may vary depending on the area of the brain and the activity involved. Despite the evidence that patterns of neural activity influence the organization of neuronal circuitry, the mechanisms involved remain elusive. Neuronal activity drives the selective survival and sprouting of branches, accompanied by the local addition of synapses, within appropriate areas furthermore, the lack of activity promotes the pruning of synaptic connections from inactive areas (Katz and Shatz, 1996). These competitive processes increase the refinement and precision of maps and require the activity of excitatory receptors (Constantine-Paton et ah, 1990 Antonini and Stryker, 1993) and locally released growth factors (Thoenen, 1995 Inoue and Sanes, 1997). 

The acute effects of ethanol and other sedative-hypnotics are mediated by actions at a number of receptor systems. For example, ethanol inhibits several excitatory receptor systems, including N-methyl-D-aspartate (NMDA) receptors, kainate receptors, and Ca channels. In addition, ethanol enhances the action of GABA at GABA receptors and appears to modulate serotonergic neurotransmission. Although a component of ethanol reinforcement is mediated by the activation of mesocorticolimbic dopamine neurons, activation of these neurons may not be necessary for ethanol reinforcement, as ethanol remains reinforcing in the absence of these neurons (Samson and Harris, 1992 Koob, 2000b). 

Recall from our discussion of cocaine and amphetamines that the body responds to the long-term abuse of these stimulants by creating more depressant receptor sites. Likewise, the body recognizes the excessive inhibitory actions produced by alcohol and tries to recover by increasing the number of synaptic receptor sites that lead to nerve excitation. A tolerance for alcohol therefore develops. To receive the same inhibitory effect, the drinker is forced to drink more, which induces the body to create even more excitable synaptic receptor sites. Eventually, an excess of these excitatory receptor sites leads to perpetual body tremors, which can be subdued either by more drinking or, with greater difficulty, by a long-term cessation of alcohol consumption. 

Cromarty, S. I. and Derby, C. D., Multiple excitatory receptor types on individual olfactory neurons implications for coding of mixtures in the spiny lobster, J. Comp. Physiol. A, 180, 481, 1997. 

In vertebrates the endogenous ligands may be glutamate, aspartate and possibly homocysteate, and the receptors are found largely in the CNS. On the basis of studies with agonists and antagonists, three main subtypes of these excitatory receptors can be distinguished. 

Serotonin agonists appear to be more potent presynaptically rather than postsynaptically. These analogs include lysergic acid diethylamide and di-methyltryptamine. Serotonin antagonists such as methysergide and cyproheptadine have little effect on central inhibitory receptors, but are quite effective on the few excitatory receptors that have been identified. No clear explanation for this apparent dichotomy has been put forth. 

Electron microscopically (Fig. 3.5), the early lesion of the neuron is marked by dendritic swelhng (Auer et al., 1985). This spares the intervening neuropil. The lesion is the electron microscopic hallmark of an excitotoxin. The reason for this is the selective dendritic location of receptors. Thns, amino acids bind to glutamate excitatory receptors on neuronal dendrites, open Ca + and Na channels which lead also to water fluxes across the membrane, and to the swelling of dendrites, sparing the intervening axons. When cell membrane breaks spread to the soma or perikaryon, the neuron dies. 

Neurophysiologic and neuropharmacologic studies indicate that N-methy 1-Dr aspartic acid (NMD A) activates a distinct set of excitatory receptors that differ from those sensitive to either quisqualic acid or kainic acid. The excitatory effects of NMDA are selectively antagonized by the divalent cation Mg as well as by D-a-amino adipate and the more potent 2-amino-4-phosphonovaleric acid (Davies et al., 1979). Olney and co-workers (1971)... 

Receptor autoradiography in the somatosensory cortex of the rat after occlusion of the arteria cerebri media revealed an increase of excitatory receptors and a decrease in GABAa receptors (Zilles etal. 1995). Using 14 nM [ H]corticosterone as radioligand, mineralocorticoid receptor binding was reduced by approximately 50 % in the hippocampus and hypothalamus of adult rats that had been born by the Caesarean procedure either with or without an added period of anoxia, in comparison to vagin-ally born controls (Boksa etal. 1996). Saturation analysis revealed that these reductions resulted from decreases in affinity of the mineralocorticoid receptor for [ H] corticosterone, with no change in numbers of receptors. 

The major neurotransmitters are listed in Table I. Typical excitatory neurotransmitters are acetylcholine, glutamate, and serotonin. They bind to receptors that are named in the same way, for instance, the acetylcholine receptor, glutamate receptor, etc. These receptors on binding their specific neurotransmitter form transmembrane channels specific for the inorganic sodium and potassium cations. They are called excitatory receptors because they shift the transmembrane potential of the cell membrane to more positive values. A change in Vm of about - -20 mV is required for the electrical signal to be transmitted to the nerve terminal where the release of a neurotransmitter is elicited. Typical inhibitory neurotransmitters are glycine... 

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