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The central respiratory generator exerts a modulatory influence on sympathetic nerve discharge. In cats the sympathoexcitatory neurons of the rostroventrolateral medulla (RVL) exhibit central respiratory modulation as well. Because RVL sympathoexcitatory neurons are largely responsible for the maintenance of sympathetic vasomotor tone, it is likely that the modulation of these neurons accounts for the central respiratory modulation of sympathetic discharge. In the present study experiments were performed to characterize the pattern of respiratory modulation of lumbar sympathetic nerve discharge (LSND) in the halothane-anesthetized rat. Phrenic-triggered averaging of LSND exhibited a small depression coincident with the onset of the phrenic burst followed by a large peak that was coincident with the cessation of the phrenic burst. Phrenic-triggered histograms of the activity of RVL sympathoexcitatory neurons exhibited three patterns of central respiratory modulation: inspiratory depression (I), inspiratory peak (II), and early inspiratory depression followed by a postinspiratory peak (III), a pattern that was very similar to that seen in LSND. Both nerve recording and single-unit recording experiments were performed in vagotomized rats with or without intact barosensory afferents. A comparison of the results suggested that, in the rat, the baroreflex does not modify or contribute to the central respiratory modulation of sympathetic output. Finally, a comparison was made between presumed nonadrenergic pacemaker-like neurons and putative C1 adrenergic neurons in the RVL. No differences were found in the patterns of central respiratory modulation.

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The role of ␣ 1 -adrenergic receptors (␣ 1 ARs) in cognition and mood is controversial, probably as a result of past use of nonselective agents. ␣ 1A AR activation was recently shown to increase neurogenesis, which is linked to cognition and mood. We studied the effects of long-term ␣ 1A AR stimulation using transgenic mice engineered to express a constitutively active mutant (CAM) form of the ␣ 1A AR. CAM-␣ 1A AR mice showed enhancements in several behavioral models of learning and memory. In contrast, mice that have the ␣ 1A AR gene knocked out displayed poor cognitive function. Hippocampal brain slices from CAM-␣ 1A AR mice demonstrated increased basal synaptic transmission, paired-pulse facilitation, and long-term potentiation compared with wild-type (WT) mice. WT mice treated with the ␣ 1A AR-selective agonist cirazoline also showed enhanced cognitive functions. In addition, CAM-␣ 1A AR mice exhibited antidepressant and less anxious phenotypes in several behavioral tests compared with WT mice. Furthermore, the lifespan of CAM-␣ 1A AR mice was 10% longer than that of WT mice. Our results suggest that long-term ␣ 1A AR stimulation improves synaptic plasticity, cognitive function, mood, and longevity. This may afford a potential therapeutic target for counteracting the decline in cognitive function and mood associated with aging and neurological disorders.