Excitatory, definition

The fact that most serotonergic dorsal raphe neurons are dependent on extrinsic excitatory or facilitatory inputs to express their characteristic spontaneous activity may seem to contradict previous studies suggesting that these neurons may function as autonomous pacemakers (42) with an endogenous rhythm (31) attributable to the presence of pacemaker potentials (8). Such a contradiction exists only if one insists that endogenous rhythms and pacemaker potentials must, by definition, be totally autonomous, i.e., completely independent of all extrinsic synaptic or neurohumoral influences. Such a definition would seem too restrictive in view of the fact that some invertebrate neurons display pacemaker potentials only when certain afferent fibers are stimulated (38) or when exposed to certain neurohumoral substances (18,28). 

In addition to epilepsy, neuronal death due to the toxic effects of glutamate has also been implicated in cerebral ischaemia associated with multi-infarct dementia and possibly Alzheimer s disease. With the plethora of selective excitatory amino acid receptor antagonists currently undergoing development, some of which are already in clinical trials, one may expect definite advances in the drug treatment of neurodegenerative disorders in the near future. 

In the mouse, whereas no evidence of H3 receptors was found in isolated gastric glands (Muller et al., 1993), in the whole stomach, (R)a-methylhistamine actually increased, and thioperamide decreased acid secretion, thus indicating a definite stimulatory role for H3 receptors in this species (Table 2). Apparently, this excitatory effect, which contrasts with the observations obtained in other models, was due to an inhibitory effect on somatostatin release from fundic D cells (Schubert et al., 1993 Vuyyuru and Schubert 1993). Also, an inhibitory effect on somatostatin secretion mediated by H3 agonists was observed in other species (rat and dog). However, contrarily to what might have been expected, in these species, the inhibitory effect on somatostatin is not followed by an increase in acid secretion, but it is instead followed by a decrease, owing to the predominant H3-mediated inhibition on the release of excitatory mediators (histamine, acetylcholine) from other sites (ECL, cholinergic nerve terminals)... 

Two different methods have been used to determine the structure-activity relations of the neurotoxic action of the excitatory amino acids. With the first, the amino acids are administered by peripheral injection, which produces neuronal damage in areas of the brain to which the excitotoxins gain access. The second approach involves direct intracranial injection with analysis of the affected area to determine the scope and specificity of the lesion. While the latter method allows for more precise definition of toxic potencies and avoids variables such as metabolism and penetration of the blood-brain barrier, the systemic administration of these compounds was exploited first and continues to be used. 

The souree of the hyperpolarization almost definitely includes either a global or regionally speeific alteration in the balance of inhibitory and excitatory neurotransmitters/neuromodulators. In the progressive brain hypoxia model, good... 

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