Nitric oxide and sympathoexcitatory cardiovascular neurons of the ventrolateral medulla in cats

In acute experiments on cats, the effects of injections of nitric oxide (NO) donors and an inhibitor of its synthesis into the sympathoexcitatory neuronal structures in the ventrolateral medulla (VLM) were studied to examine their effects on the peripheral mechanisms of the cardiovascular control. Unilateral injections of NO donors, nitroglycerine (1.3–5.2 nmol) or sodium nitroprusside (1.1–4.6 nmol) into the sites of the sympathoexcitatory neurons residing in the VLM induced the lowering of the systemic arterial pressure (SAP) in a dose-depended fashion. Two types of the hypotensive responses have been distinguished. In the first type responses, lowering of the SAP level was mainly due to a decrease in the peripheral vascular resistance (PVR), while the heart rate (HR) and stroke volume (SV) were only slightly reduced. In the second type responses, the drop in SAP level resulted mainly from a decrease in the HR and myocardial contractivity. These effects were induced by the limitation of the descending excitatory influences to the heart and vessels from the VLM sympathoexcitatory systems. An increase in the NO concentrations in the neuronal structures located 2.5–4.5 mm caudally to the trapezold bodies resulted in the first type responses, while that in the sites immediately adjacent to the caudal sympathoinhibitory area (0.5–1.5 mm rostrally to the XIIth cranial nerve roots) was associated with the second type of reactions. Stimulation of the endogenous NO release from the neurons after injections of L-arginine induced the same cardiovascular shifts as exogenic NO did, and attenuation of NO synthesis following injections of NO antagonist L-NMMA into the VLM neuronal structures evoked hemodynamic shifts of a reverse direction. Injections of NO donors inhibited the reflex responses induced by the activation of the carotid sinus receptors. Our data give further evidence for NO involvement in the inhibitory control of the cardiac activity and vascular tone through those VLM sympatoexcitatory neurons, which are involved in the system of central neurogenic cardiovascular control and the activity of which prevent the development of hypertension.Neirofiziologiya/Neurophysiology, Vol. 28, No. 2/3, pp. 111–120, March–June, 1996.     

Immunohistochemical studies on GABAergic neurons in the rat locus coeruleus, with special reference to their relationship to astrocytes

Purified antisera against GABA were prepared. A few small GABAergic neurons in the rat locus coeruleus were immunohistochemically demonstrated by both the unlabeled peroxidase-antiperoxidase method and the avidin-biotin peroxidase complex method using affinity-purified GABA antibodies. The glial fibrillary acidic protein immunoreactivity in this nucleus was localized by the latter method in the astrocytal framework encircling medium-sized and small neurons as well as in straight processes. Astrocytes may play a role as energy donors to these neurons.     

Responses of neurons in the rostral ventrolateral medulla to whole body rotations: comparisons in decerebrate and conscious cats

The responses to vestibular stimulation of brain stem neurons that regulate sympathetic outflow and blood flow have been studied extensively in decerebrate preparations, but not in conscious animals. In the present study, we compared the responses of neurons in the rostral ventrolateral medulla (RVLM), a principal region of the brain stem involved in the regulation of blood pressure, to whole body rotations of conscious and decerebrate cats. In both preparations, RVLM neurons exhibited similar levels of spontaneous activity (median of ～17 spikes/s). The firing of about half of the RVLM neurons recorded in decerebrate cats was modulated by rotations; these cells were activated by vertical tilts in a variety of directions, with response characteristics suggesting that their labyrinthine inputs originated in otolith organs. The activity of over one-third of RVLM neurons in decerebrate animals was altered by stimulation of baroreceptors; RVLM units with and without baroreceptor signals had similar responses to rotations. In contrast, only 6% of RVLM neurons studied in conscious cats exhibited cardiac-related activity, and the firing of just 1% of the cells was modulated by rotations. These data suggest that the brain stem circuitry mediating vestibulosympathetic reflexes is highly sensitive to changes in body position in space but that the responses to vestibular stimuli of neurons in the pathway are suppressed by higher brain centers in conscious animals. The findings also raise the possibility that autonomic responses to a variety of inputs, including those from the inner ear, could be gated according to behavioral context and attenuated when they are not necessary.     

Horseradish peroxidase-positive neurons of nonspecific thalamic nuclei projecting to the primary somatosensory cortex in cats

The morphology and topography of neurons whose axons form the nonspecific thalamic input in the primary somatosensory area were studied in the cat forebrain by the retrograde axonal horseradish peroxidase transport method. Stained cells were found in the dorsolateral part of the nucleus ventralis anterior, and were diffusely distributed in the nucleus centralis, lateralis, the lateral part of the nucleus dorsalis medialis, and the dorsal part of the centrum medianum. In the nucleus paracentralis only solitary, palely stained neurons were detected. Cells stained with horse-radish peroxidase were multipolar, triangular, or fusiform. The results are evidence that besides the ventrobasal complex, the nonspecific nuclei of the diencephalon also project into the somatosensory cortex. This indicates the existence of multiple afferent thalamic inputs into the somatic cortex.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 11, No. 5, pp. 435–440, September–October, 1979.     

Impulse response of neurons of the thalamic reticular nucleus to extraneous stimulation in conditioned-reflex trained cats

During heteromodal extraneous stimulation (ES), a large part of responding neurons of the thalamic reticular nucleus (RN) exhibit selectivity by responding with excitation to the stimulation of only one type of sensory input. To visual ES, 12 of 32 tested neurons responded; and 4 of 21 tested neurons responded to auditory ES. Response of neurons to ES diminished during the process of habituation to these stimuli; and after habituation was completed, the number of neurons responsive to the ES also diminished. Use of ES led to disappearance of high-frequency, grouped discharges in the responses of the RN neurons. Initial responses to ES and to the following conditioning stimulus (CS) appeared during external inhibition of the conditioned reflex (CR), but the later components of impulse responses that ordinarily accompany realized CR were suppressed in nearly one half of the studied neurons. We reach the conclusion that RN neurons participate in external inhibition of CR and in habituation to ES.A. A. Bogomolets Physiology Institute, Academy of Sciences of the USSR, Kiev. Translated from Neirofiziologiya, Vol. 23, No. 2, pp. 189–199, March–April, 1991.     

Comparative genomics of the endocrine systems in humans and chimpanzees with special reference to GNRH2 and UCN2 and their receptors

To identify the genetic basis of the differences between chimpanzees and humans, it is indispensable to analyze a whole gene set constituting a particular regulatory system as well as to compare the whole genome or chromosomes randomly. We compared genes encoding hormones of the endocrine system, one of the most fundamental regulatory systems in organisms. The present study covered a total of 111 genes generating 115 precursors and 172 peptides. Decisive differences were observed in GNRH2 and UCN2 and their corresponding receptor genes. It is often postulated that mechanisms underlying the basic functions of life are common and would not be readily altered. The present study demonstrated that, on the contrary, substantial differences have been generated in genes composing the endocrine system, even between humans and our closest living relative.     

Dental morphometric variation between African and Asian colobines, with special reference to the other Old World monkeys

In order to reveal differences between Asian and African colobines (nonhuman primates) in terms of dietary adaptation and evolutionary development, a large number of the species of the cercopithecoids (Old World monkeys) was analyzed with morphometric methods. In addition to the raw data and ratios, deviations of the colobines, predicted from allometric baselines derived from the cercopithecines, were analyzed by univariate and multivariate analyses. Some results indicated that there exists significant differentiation between colobines and cercopithecines; the latter exhibit a larger dental scale relative to body size, and the less developed front teeth of the colobines may be related to their fewer frequent incisal use, compared with those of the cercopithecines. With regard to variations between the two subtribes of the colobines, which are found in African (Colobina) and Asia (Presbytina), the Asian subtribe displays a larger scale of postcanine teeth, referring to the results of the raw data. This may correspond to their larger body size. While ratios were considered, the variation between Presbytina and Colobina was diminished greatly. This implies that, unlike the scenario postulated to reflect the relationships between colobines and cercopithecines--which supposes that their differentiation is in both size and shape--the variation between the two subtribes is principally size associated: relative to body size Colobina exhibits more emphasized incisors, but less developed postcanine teeth--with the exception of width of M3s. In other words, the relationships between teeth and body size of the African colobines are more similar to those of the cercopithecines. This implies, compared to their Asian partners, that African colobines share more similarities with cercopithecines. This may be related to the episodes in which African species underwent a longer period of sharing environmental and climatic patterns with the cercopithecines that moved to Asia about 5 or 8 million years ago. Canines were found to be important in distinguishing colobines from cercopithecines and in separating one subtribe from the other.     

Unit responses of the thalamic and ventral anterior thalamic nuclei to electrical stimulation of thalamic relay nuclei in cats

Responses of 92 neurons of the reticular (R) and 105 neurons of the ventral anterior (VA) thalamic nuclei to stimulation of the ventrobasal complex (VB) and the lateral (GL) and medial (GM) geniculate bodies were investigated in cats immobilized with D-tobocurarine. Altogether 72.2% of R neurons and 76.2% of VA neurons responded to stimulation of VB whereas only 15.0% of R neurons and 27.1% of VA neurons responded to stimulation of GM and 10.2% of R neurons and 19.6% of VA neurons responded to stimulation of GL. The response of the R and VA neurons to stimulation of the relay nuclei as a rule was expressed as excitation. A primary inhibitory response was observed for only two R and three VA neurons. Two types of excitable neurons were distinguished: The first respond to afferent stimulation by a discharge consisting of 5–15 spikes with a frequency of 250–300/sec; the second respond by single action potentials. Neurons of the first type closely resemble inhibitory interneurons in the character of the response. Antidromic responses were recorded from 2.2% of R neurons and 7.8% of VA neurons during stimulation of the relay nuclei. Among the R and VA neurons there are some which respond to stimulation not only of one, but of two or even three relay nuclei. If stimulation of one relay nucleus is accompanied by a response of a R or VA neuron, preceding stimulation of another nucleus leads to inhibition of the response to the testing stimulus if the interval between conditioning and testing stimuli is less than 30–50 msec.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 8, No. 6, pp. 597–605, November–December, 1976.     

Rhythmic activity of neurons in the rostral ventrolateral medulla of conscious cats: effect of removal of vestibular inputs

Although it is well established that bulbospinal neurons located in the rostral ventrolateral medulla (RVLM) play a pivotal role in regulating sympathetic nerve activity and blood pressure, virtually all neurophysiological studies of this region have been conducted in anesthetized or decerebrate animals. In the present study, we used time- and frequency-domain analyses to characterize the naturally occurring discharges of RVLM neurons in conscious cats. Specifically, we compared their activity to fluctuations in carotid artery blood flow to identify neurons with cardiac-related (CR) activity; we then considered whether neurons with CR activity also had a higher-frequency rhythmic firing pattern. In addition, we ascertained whether the surgical removal of vestibular inputs altered the rhythmic discharge properties of RVLM neurons. Less than 10% of RVLM neurons expressed CR activity, although the likelihood of observing a neuron with CR activity in the RVLM varied between recording sessions, even when tracking occurred in a very limited area and was higher after vestibular inputs were surgically removed. Either a 10-Hz or a 20- to 30-Hz rhythmic discharge pattern coexisted with the CR discharges in some of the RVLM neurons. Additionally, the firing rate of RVLM neurons, including those with CR activity, decreased after vestibular lesions. These findings raise the prospect that RVLM neurons may or may not express rhythmic firing patterns at a particular time due to a variety of influences, including descending projections from higher brain centers and sensory inputs, such as those from the vestibular system.     

Pancreatic APUD cells in older chick embryos,with special reference to their identity

Summary Pancreatic APUD cells showing formaldehyde-induced fluorescence in Black Australorp chick embryos of nine to eighteen days of incubation, proved, on subsequent staining and silver impregnation, to be A, B, D and, from sixteen days, enterochromaffin (EC) cells. EC and D cells were scattered in the exocrine parenchyma, the latter cells increasing with time. Some groups of B cells were associated with large A islets from the ninth day of incubation onwards. The composition of A islets (A and some D cells) and B islets (B and some D cells) and the distribution attained (A islets in the splenic and third lobes; B islets in all lobes), accords with the situation reported for adults.     

Differential expression of the GABA transporters GAT-1 and GAT-3 in brains of rats,cats, monkeys and humans

The homeostasis of GABA is critical to normal brain function. Extracellular levels of GABA are regulated mainly by plasmalemmal gamma-aminobutyric acid (GABA) transporters. Whereas the expression of GABA transporters has been extensively studied in rodents, validation of this data in other species, including humans, has been limited. As this information is crucial for our understanding of therapeutic options in human diseases such as epilepsy, we have compared, by immunocytochemistry, the distributions of the GABA transporters GAT-1 and GAT-3 in rats, cats, monkeys and humans. We demonstrate subtle differences between the results reported in the literature and our results, such as the predominance of GAT-1 labelling in neurons rather than astrocytes in the rat cortex. We note that the optimal localisation of GAT-1 in cats, monkeys and humans requires the use of an antibody against the human sequence carboxyl terminal region of GAT-1 rather than against the slightly different rat sequence. We demonstrate that GAT-3 is localised mainly to astrocytes in hindbrain and midbrain regions of rat brains. However, in species such as cats, monkeys and humans, additional strong immunolabelling of oligodendrocytes has also been observed. We suggest that differences in GAT distribution, especially the expression of GAT-3 by oligodendrocytes in humans, must be accommodated in extrapolating rodent models of GABA homeostasis to humans.Grant support was provided by the National Health and Medical Research Council (Australia) grant nos. 210127 and 102448, and a Senior Research Fellowship to David Pow.