Neuroscience
-
Circulating angiotensin II acts on neurons in circumventricular organs, leading to activation of central pathways involved in blood pressure regulation and body fluid homeostasis. Apart from this primary effect, an increase in the level of circulating angiotensin II may also activate brain neurons as a secondary consequence of the associated increase in blood pressure, which will stimulate arterial baroreceptors and thus activate central neurons that are part of the central baroreceptor reflex pathway. The aim of this study was to identify the population of neurons that are activated as a consequence of the direct actions of circulating angiotensin II on the brain, independent of secondary baroreceptor-mediated effects. ⋯ In these animals, the pattern of Fos expression was similar to that evoked in barointact rabbits infused at the lower rate, but the degree of Fos expression in all medullary regions and in some forebrain regions was significantly greater. The results of the present study, together with those of previous studies from our laboratory in which we determined the effects of phenylephrine-induced hypertension on brain Fos expression [Li and Dampney (1994) Neuroscience 61, 613-634; Potts et al. (1997) Neuroscience 77, 503-520], indicate that in conscious rabbits circulating angiotensin II activates primarily circumventricular neurons within the organum vasculosum of the lamina terminalis and subfornical organ, but not the area postrema, and this in turn leads to activation of neurons in other forebrain regions, including the median preoptic, supraoptic, paraventricular and suprachiasmatic nucleus as well as the bed nucleus of the stria terminalis. In contrast, the activation of neurons in medullary regions evoked by an increase in the level of circulating angiotensin II is primarily a secondary effect resulting from stimulation of arterial baroreceptors.
-
The dorsal regions of the midbrain and pons have been found to participate in sleep regulation. However, the physiological role of the ventral brainstem in sleep regulation remains unclear. We used N-methyl-D-aspartate-induced lesions of the ventral midbrain and pons to address this question. ⋯ These changes are comparable in magnitude to those seen after basal forebrain lesions. Neuronal degeneration was found in the ventral rostral pons and midbrain, including the substantia nigra, ventral tegmental area, retrorubral nucleus, and ventral mesencephalic and rostroventral pontine reticular formation. We conclude that nuclei within the ventral mesencephalon and rostroventral pons play an important role in sleep regulation.
-
Prolonged nociceptive input following peripheral injury results in hyperalgesia (enhanced response to a noxious stimulus), which is thought to occur as a consequence of sensitization of primary afferent nociceptors and enhanced excitability of spinal dorsal horn nociceptive neurons (central sensitization). Since there is often an expansion of hyperalgesia to tissue adjacent, and even distant from the site of injury (secondary hyperalgesia), it is thought that this phenomenon primarily involves mechanisms of central modulation/plasticity. In contrast, hyperalgesia observed at the site of tissue injury (primary hyperalgesia) involves peripheral mechanisms. ⋯ The effect of bilateral rostral medial medulla lesions produced by the soma-selective neurotoxin ibotenic acid was determined in three different models of cutaneous thermal hyperalgesia following peripheral inflammation: (i) intraplantar injection of carrageenan into the hindpaw (model of primary hyperalgesia); (ii) intra-articular injection of carrageenan/kaolin into the knee of the hind leg (model of secondary hyperalgesia); and (iii) topical application of mustard oil to the hind leg (model of secondary hyperalgesia). Compared with sham lesion animals, a bilateral lesion of the rostral medial medulla completely blocked thermal hyperalgesia in the two models of secondary hyperalgesia (intra-articular carrageenan/kaolin injection into the knee and topical mustard oil application to the hind leg), but was ineffective in blocking facilitation of the thermal paw withdrawal response in the model of primary hyperalgesia (intraplantar carrageenan injection into the hindpaw). These results suggest that primary and secondary hyperalgesia are differentially modulated in the CNS, and support the notion that descending nociceptive facilitatory influences from the rostral medial medulla significantly contribute to secondary, but not primary, hyperalgesia.