Neuroscience
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Comparative Study
Adenosine A2 receptors: selective localization in the human basal ganglia and alterations with disease.
Adenosine A2 receptors were labeled and visualized by autoradiography in tissue sections of the human brain using the A2-selective agonist ligand [3H](2-p-(2-carboxyethyl)phenylamino)-5'-N-carboxamidoadenosine (CGS 21680). The binding of this ligand was of high affinity, reversible, and was blocked by adenosine A2 agents. Autoradiographic mapping of adenosine A2 sites revealed them to be exclusively restricted to the caudate nucleus, putamen, nucleus accumbens, olfactory tubercle and the lateral segment of the globus pallidus. ⋯ In contrast, density values of A2 sites were dramatically decreased, compared to control values, in the basal ganglia of patients with Huntington's chorea. Similar losses of A2 receptors were observed in the guinea-pig striatum after local application of quinolinic acid while lesioning of the dopaminergic neurons was without effect. All these results taken together suggest that adenosine A2 receptors are localized on striatal output neurons which degenerate in Huntington's chorea.
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The localization and distribution of quinolinic acid phosphoribosyltransferase, the degradative enzyme of the endogenous excitotoxin quinolinic acid, were studied in the post mortem human neostriatum by immunohistochemistry. In eight neurologically normal human brains, quinolinic acid phosphoribosyltransferase immunoreactivity was detected in both glial cells and neurons. Typically, glial cells containing quinolinic acid phosphoribosyltransferase immunoreactivity had numerous processes radiating from the cell bodies. ⋯ The somatic and dendritic morphology of quinolinic acid phosphoribosyltransferase-immunoreactive neurons closely resembles that of aspiny neurons seen in Golgi preparations. The localization of the specific quinolinic acid-catabolizing enzyme in distinct populations of neostriatal cells suggests specific functional correlates. It remains to be examined how the anatomical organization of quinolinic acid phosphoribosyltransferase immunoreactivity relates to the degradation of quinolinic acid in the striatum, and if the morphological characteristics and distribution of quinolinic acid phosphoribosyltransferase-immunoreactive cells are of relevance for the pathogenesis of neurodegenerative basal ganglia disorders.
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The organization of connections between the amygdala, prefrontal cortex and striatum was studied using anterograde and retrograde tract tracing techniques in the rat. The anterograde transport of Phaseolus vulgaris leucoagglutinin and wheat germ agglutinin conjugated to horseradish peroxidase was used to examine the striatal projections of the prefrontal cortex. These studies revealed that the prelimbic area of the medial prefrontal cortex projects mainly to the medial part of the striatum, whereas the dorsal agranular insular area of the lateral prefrontal cortex projects mainly to the ventrolateral part of the striatum. ⋯ The rostral pole and lateral portions of the basolateral nucleus project to both the lateral prefrontal cortex and its associated lateral striatal region. Many neurons in the basolateral amygdaloid nucleus, and to a lesser extent other amygdaloid nuclei, were double-labeled in these experiments, indicating that these cells send collaterals to both the prefrontal cortex and striatum. These findings indicate that discrete areas of the amygdala, and in some cases individual amygdaloid neurons, can modulate information processing in the first two links of distinct cortico-striato-pallidal systems arising in the medial and lateral prefrontal cortex.
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The effects of elevated CO2 (i.e. hypercapnia) on neurons in the nucleus tractus solitarii were studied using extracellular (n = 82) and intracellular (n = 33) recording techniques in transverse brain slices prepared from rat. Synaptic connections from putative chemosensitive neurons in the ventrolateral medulla were removed by bisecting each transverse slice and discarding the ventral half. In addition, the response to hypercapnia in 20 neurons was studied during high magnesium-low calcium synaptic blockade. ⋯ These neurons were not driven synaptically by putative chemosensitive neurons of the ventrolateral medulla since this region was removed from the slice. Furthermore, because chemosensitivity persisted in most neurons tested during synaptic blockade, we conclude that some neurons in the nucleus tractus solitarii are inherently CO2-chemosensitive. Although the function of dorsal medullary chemosensitive neurons cannot be determined in vitro, their location and their inherent chemosensitivity suggest a role in cardiorespiratory central chemoreception.
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Electrical stimuli were applied to tooth-pulp in cats and the thresholds of the jaw-opening reflex and of neurons in the trigeminal sensory nuclei were determined. The effects of the method of preparation of the animal for stereotaxic recording were determined by making observations on animals set up in one of three ways: acutely in the usual manner; chronically, three to five days before recording; and acutely with precautions to minimize nociceptive input to the central nervous system. The threshold of the jaw-opening reflex increased progressively during the setting up of the normal, acute preparations and at the time brainstem recording began was significantly higher in these than in either the chronic or low-trauma acute preparations. ⋯ In the chronic and in low-trauma acute preparations, there was no significant difference between the thresholds of the units in the main sensory trigeminal nucleus and spinal subnucleus oralis compared with those in subnucleus caudalis. Thus the preparation of an animal for stereotaxic recording can cause a severe and long-lasting depression in the excitability of neurons in the trigeminal sensory nuclei and an increase in the threshold of the jaw-opening reflex. This effect will have influenced the results of previous studies on the responses evoked in central neurons by stimulation of tooth-pulp, and may have similarly affected recordings from other regions.