Caudal Neurons Research Articles

Newborn rat brainstem preparation with the trigeminal nerve attached for pain study

Studies using a brainstem–spinal cord preparation isolated from newborn rats have provided substantial information on neuro-physiology, -pharmacology and -anatomy of the respiratory center, such as mechanisms of respiratory rhythm generation, development of a respiratory center or respiratory reflex [T. Murakoshi, T. Suzue, S. Tamai, A pharmacological study on respiratory rhythm in the isolated brainstem–spinal cord preparation from newborn rat, Br. J. Pharmac. 86 (1985) 95–104 [5]; H. Onimaru, A. Arata, I. Homma, Primary respiratory rhythm generator in the medulla of brainstem–spinal cord preparations from newborn rats, Brain Res. 445 (1988) 314–324 [6]; H. Onimaru, I. Homma, Whole cell recordings from respiratory neurons in the medulla of brainstem–spinal cord preparations isolated from newborn rats, Pflügers Arch. 420 (1992) 399–406 [7]; J.C. Smith, K. Ballanyi, D.W. Richter, Whole-cell patch clamp recordings from respiratory neurons in neonatal rat brainstem in vitro, Neurosci. Lett. 314 (1992) 153–156 [10]; T. Suzue, Respiratory rhythm generation in the in vitro brainstem–spinal cord preparation of the neonatal rat, J. Physiol. (London) 354 (1984) 173–183 [11], reviewed in H. Onimaru, A. Arata, I. Homma, Neuronal mechanisms of respiratory rhythm generation: An approach using in vitro preparation, Jpn. J. Physiol. 47 (1997) 385–403 [8]]. Recently, the dissecting method of the preparation was modified to introduce a brainstem preparation with the trigeminal primary afferents attached for pain studies [M. Hamba, Repetitive stimulation potentiated the stimulus-evoked firing in the trigeminal caudalis—in vitro study. Neurosci. Res. 20 (1996) s163 [2]; M. Hamba, Stimulation-induced responses of the trigeminal caudal neurons in the brainstem preparation isolated from newborn rats, Brain Res. 785 (1998) 66–74 [3]]. As reported previously [3], the activity-dependent change in the excitability of pain-processing neurons, wind-up phenomenon, was studied in the trigeminal caudalis by stimulating the mandibular nerve, using a modified brainstem preparation isolated from newborn rats. The caudalis, the medulla dorsal horn, is known as the center for processing pain and sensory information from the cranio-facial area. The results indicated that the brainstem preparation is applicable for studies on the neuroplasticity at the pain-processing synapses. Here, we describe the method for isolation of a brainstem preparation with the trigeminal mandibular nerve attached and for recording the synaptic response evoked in the caudal neurons, using a whole-cell patch clamp technique. In the present study, we demonstrated repetitive stimulation-induced responses of caudal neurons at postnatal day 1 as an example showing the feasibility of the preparation for pain studies. Themes: Sensory systems Topics: Pain modulation: anatomy and physiology

Longitudinal distribution of components of excitatory synaptic input to motoneurones during swimming in young Xenopus tadpoles: experiments with antagonists.

1. Recent studies have revealed that the excitatory synaptic input to spinal motoneurones during fictive swimming in Xenopus tadpoles has three main components: glutamatergic (Glu) from premotor excitatory interneurones, nicotinic cholinergic (nACh) from more rostral motoneurones, and electrotonic coupling from neighbouring motoneurones. During swimming, these components sum to produce two kinds of excitation: phasic excitation (EPSPs) underlying spikes, and tonic depolarization. 2. We have investigated the longitudinal distribution of these excitatory synaptic inputs to presumed motoneurones at different positions along the spinal cord using intracellular recording techniques. Different antagonists (10 microM dihydro-beta-erythroidine (DHbetaE) for nicotinic ACh receptors (nAChRs), 2 mM kynurenate (Kyn) for glutamate receptors (GluRs), and 100 microM Cd2+ for all chemical synapses) were microperfused very locally to unmask the relative contributions of these components to the total excitatory drive, and their distribution along the spinal cord during swimming. 3. If the potentials remaining when all chemical components were blocked by Cd2+ were subtracted from potentials recorded after blocking nAChRs and GluRs with DHbetaE plus Kyn, a small unidentified component was observed. This component was blocked by the specific AMPA antagonist 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (NBQX, 5 microM), so is glutamate mediated. 4. We used the potential measurements to calculate the relative synaptic conductances of the different synaptic inputs, and conclude that: (a) there is a rostral-caudal gradient in input during EPSPs and tonic depolarization; (b) the glutamatergic component accounts for most of the excitation, and decreases caudally; (c) cholinergic and electrotonic components are relatively constant in different positions along the spinal cord; and (d) these two components provide an increasing proportion of the input in more caudal neurones. 5. We propose that the glutamate components of excitation are fundamental to rhythm generation in the brainstem and rostral cord, while the electrotonic and cholinergic components ensure that the central pattern generator activates motoneurones effectively in all parts of the spinal cord.

Expectation of reward modulates cognitive signals in the basal ganglia.

Action is controlled by both motivation and cognition. The basal ganglia may be the site where these kinds of information meet. Using a memory-guided saccade task with an asymmetric reward schedule, we show that visual and memory responses of caudate neurons are modulated by expectation of reward so profoundly that a neuron's preferred direction often changed with the change in the rewarded direction. The subsequent saccade to the target was earlier and faster for the rewarded direction. Our results indicate that the caudate contributes to the determination of oculomotor outputs by connecting motivational values (for example, expectation of reward) to visual information.

Chemical stimulation of the intracranial dura induces enhanced responses to facial stimulation in brain stem trigeminal neurons.

Chemical activation and sensitization of trigeminal primary afferent neurons innervating the intracranial meninges have been postulated as possible causes of certain headaches. This sensitization, however, cannot explain the extracranial hypersensitivity that often accompanies headache. The goal of this study was to test the hypothesis that chemical activation and sensitization of meningeal sensory neurons can lead to activation and sensitization of central trigeminal neurons that receive convergent input from the dura and skin. This hypothesis was investigated by recording changes in the responsiveness of 23 [16 wide-dynamic range (WDR), 5 high threshold (HT), and 2 low threshold (LT)] dura-sensitive neurons in nucleus caudalis to mechanical stimulation of their dural receptive fields and to mechanical and thermal stimulation of their cutaneous receptive fields after local application of inflammatory mediators or acidic agents to the dura. Responses to brief chemical stimulation were recorded in 70% of the neurons; most were short, lasting the duration of the stimulus only. Twenty minutes after chemical stimulation of the dura, the following changes occurred: 1) 95% of the neurons showed significant increases in sensitivity to mechanical indentation of the dura: their thresholds to dural indentation changed from 1.57 to 0.49 g (means, P < 0.0001), and the response magnitude to identical stimuli increased by two- to fourfold; 2) 80% of the neurons showed significant increases in cutaneous mechanosensitivity: their responses to brush and pressure increased 2.5- (P < 0.05) and 1. 6-fold (P < 0.05), respectively; 3) 75% of the neurons showed a significant increase in cutaneous thermosensitivity: their thresholds to slow heating of the skin changed from 43.7 +/- 0.7 to 40.3 +/- 0.7 degrees C (P < 0.005) and to slow cooling from 23.7 +/- 3.3 to 29.2 +/- 1.8 degrees C (P < 0.05); 4) dural receptive fields expanded within 30 min and cutaneous receptive fields within 2-4 h; and 5) ongoing activity developed in WDR and HT but not in LT neurons. Application of lidocaine to the dura abolished the response to dural stimulation but had minimal effect on the increased responses to cutaneous stimulation (suggesting involvement of a central mechanism in maintaining the sensitized state). Antidromic activation (current of <30 muA) of dura-sensitive neurons revealed projections to the hypothalamus, thalamus, and midbrain. These findings suggest that chemical activation and sensitization of dura-sensitive peripheral nociceptors could lead to enhanced responses in central neurons and that this central sensitization therefore could result in extracranial tenderness (mechanical and thermal allodynia) in the absence of extracranial pathology. The projection targets of these neurons suggest a possible role in mediating the autonomic, endocrine, and affective symptoms that accompany headaches.

Stimulation-induced responses of the trigeminal caudal neurons in the brainstem preparation isolated from newborn rats

The brainstem preparation with the trigeminal mandibular nerve attached was isolated from rats postnatal day 0–6 (P0–P6) to test if the potentiation could be induced in neonatal neurons in the trigeminal subnucleus caudalis by stimulation of the primary afferents. The stimulation-induced potentials in 92 neurons recorded extracellularly, and the synaptic potentials in 16 neurons recorded by the whole-cell patch clamp technique were examined. The extracellularly recorded neurons responded to stimulation (0.5 Hz) with either an increase, a decrease, or little change in spike numbers, and were classified as Type 1, Type 2, and Type 3, respectively. Type 1 neurons at P4 and older responded in a low Mg 2+ solution with a progressive increase in spike number lasting for several minutes after the cessation of stimulation, i.e., short-term potentiation, STP. This potentiation was antagonized by 20 μM of (+)-MK-801 hydrogen maleate (MK-801) or 25 μM of 2-amino-5-phosphonovaleric acid. In contrast, Type 1 at P3 and younger did not exhibit STP. The age-related distinct response properties were observed between Type 1 neurons at P4–P6 and at P0–P3. The percentage of Type 1 in studied neurons increased from 24% at P0–P3 to 53% at P4–P6. In the intracellular experiment, the mean latency of excitatory postsynaptic potential (EPSP) of recorded neurons indicated that the conduction velocity of the convergent afferents was 0.37 m/s, in the range of C-fiber. Neurons were classified as Type E and Type I. Type E responded with EPSP only, or with both EPSP and inhibitory postsynaptic potentials (IPSP), while Type I responded with IPSP only. In Type E at P4 and older, a single stimulation produced a burst of spike discharges that lasted for several seconds. Stimulation at a hyperpolarized membrane potential showed that aggregated slow EPSPs lay under a burst of spike discharges, and that slow EPSPs, but not a short-latency EPSP, were completely blocked by MK-801. In contrast, Type E at P3 and younger did not evoke a burst of spikes. Morphological examination of recorded neurons showed that the formation of networks was sparse at P1 and rapidly developed up to P4. The results suggest that: (1) short-term potentiation is induced with the development of synaptic network formation in the caudal nucleus at P4 and older; (2) the summation of N-methyl- d-aspartate (NMDA)-mediated slow EPSPs build up a prolonged depolarization; and (3) the brainstem preparation is applicable for neurophysiological studies on the trigeminal pain system.

The caudal neurosecretory system and its afferent synapses in the goldfish, Carassius auratus: Morphology, immunohistochemistry, and fine structure

Morphological features of the goldfish caudal neurosecretory system were investigated by means of immunohistochemical localization of urotensins I and II (UI and UII) and electron microscopic examination of the caudal neurosecretory neurons, the urophysis, and the synaptic neuropil. The aim of the work is to provide a detailed morphological description of the afferent synapses to the caudal neurons and to analyze their distribution through the rostrocaudal extension of the caudal neurosecretory system. Three morphologically different types of neurosecretory cells have been identified according to size and shape: large, medium, and small Dahlgren cells. The three different-sized cells share similar patterns of immunoreactivity with the UI (or oCRF) and the UII antisera. Electron microscopic examination of the synaptic neuropil throughout the caudal system revealed the presence of four types of terminals: dense-cored-vesicle end bulbs (DC), spherical-vesicle end bulbs (S), flattened-vesicle end bulbs (F), and granular-vesicle end bulbs (G). The present study demonstrates that the small Dahlgren cells receive different synaptic inputs from the large and the medium neurosecretory cells. Indeed, G terminals are only found on the small Dahlgren cells, whereas DC, S, and F terminals are distributed on the large, medium, and small Dahlgren cell bodies and proximal processes. J. Morphol. 235:59–76, 1998. © 1998 Wiley-Liss, Inc.

The caudal neurosecretory system and its afferent synapses in the goldfish, Carassius auratus: morphology, immunohistochemistry, and fine structure.

Morphological features of the goldfish caudal neurosecretory system were investigated by means of immunohistochemical localization of urotensins I and II (UI and UII) and electron microscopic examination of the caudal neurosecretory neurons, the urophysis, and the synaptic neuropil. The aim of the work is to provide a detailed morphological description of the afferent synapses to the caudal neurons and to analyze their distribution through the rostrocaudal extension of the caudal neurosecretory system. Three morphologically different types of neurosecretory cells have been identified according to size and shape: large, medium, and small Dahlgren cells. The three different-sized cells share similar patterns of immunoreactivity with the UI (or oCRF) and the UII antisera. Electron microscopic examination of the synaptic neuropil throughout the caudal system revealed the presence of four types of terminals: dense-cored-vesicle end bulbs (DC), spherical-vesicle end bulbs (S), flattened-vesicle end bulbs (F), and granular-vesicle end bulbs (G). The present study demonstrates that the small Dahlgren cells receive different synaptic inputs from the large and the medium neurosecretory cells. Indeed, G terminals are only found on the small Dahlgren cells, whereas DC, S, and F terminals are distributed on the large, medium, and small Dahlgren cell bodies and proximal processes.

Changes in neurons of the caudate nucleus in experimental alcoholism

Reversible changes in caudate neurons and their dendrites in line with the components of compensatory reaction in oligodendrocytes are observed in rats during the first 3 weeks of a 12-month alcoholization period. After 2–4 months of alcoholization (the development of dependency), degenerative changes occur in caudate neurons and their dendrites system were evident. By the end of the 12-month period of alcohol intoxication, intensified deafferentation of the dendritic system was observed, suggesting functional insufficiency of the caudate nucleus.

Type 2 metabotropic glutamate (mGlu) receptors tonically inhibit transmitter release in rat caudate nucleus: in vivo studies with (2S,1'S,2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine, a new potent and selective antagonist.

Anatomical, biochemical and electrophysiological studies have previously shown that cortico-striatal terminals contain abundant presynaptic group 2 metabotropic glutamate (mGlu) receptors. Using brain slices we have previously shown that these receptors inhibit depolarization-induced transmitter release. Using microdialysis in freely moving rats, we now report the effects of group 2 mGlu receptor agonists and antagonists on glutamate concentration in the caudate extracellular fluid. A mild decrease (20-30%) in glutamate concentration in caudate dialysates was observed when 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid or (2S,3S,4S)-alpha-carboxycyclopropyl-glycine (L-CCG-1), mGlu receptor agonists, was locally administered. On the contrary, alpha-methyl-4-carboxyphenylglycine, an antagonist of type 1 and type 2 mGlu receptors, increased the glutamate concentration in dialysates by up to 3.5-fold, and its effects were prevented by the simultaneous administration of L-CCG-1, a preferential type 2 mGlu receptor agonist. A significant increase of glutamate output in striatal dialysate was also found after local administration of (2S,1'S,2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine, another structurally unrelated, relatively selective and potent type 2 mGlu receptor antagonist. The results suggest that type 2 mGlu receptors tonically inhibit transmitter release from cortico-striatal terminals. Since the cortico-striatal pathway profoundly affects the function of a large percentage of caudate neurons, it is reasonable to predict that the use of selective type 2 mGlu receptor agents will be helpful for scientific and therapeutic studies on the physiopathology of basal ganglion disorders.

KATP-channel on the somata of spiny neurones in rat caudate nucleus: regulation by drugs and nucleotides.

1. The aim of the present study was to characterize the pharmacological properties of the adenosine 5'-triphosphate(ATP)-sensitive K+ channel (KATP-channel) on the somata of spiny neurones in rat caudate nucleus and to compare them with those of beta-cells. For that purpose we tested the effects of several KATP-channel-inhibiting and -activating drugs on the opening activity of the KATP-channel in caudate nucleus by use of the patch-clamp technique. In addition, the modulation of drug responses by cytosolic nucleotides was examined. 2. When KATP-channels in caudate nucleus were activated in cell-attached patches by inhibition of mitochondrial energy production, meglitinide (a benzoic acid derivative), Hoe36320 (a sulphonylurea of low lipophilicity) and glipizide reduced KATP-channel activity half-maximally at 0.4 microM, 0.4 microM and about 0.5 nM, respectively. 3. In inside-out patches (presence of 0.7 mM free Mg2+ at the cytoplasmic membrane side), tolbutamide (0.1 mM) caused only partial inhibition of KATP-channels in the absence of cytosolic nucleotides but complete inhibition in the simultaneous presence of the channel-activating nucleotide guanosine 5'-diphosphate (GDP; 1 mM) and the channel-inhibiting nucleotide adenylyl-imidodiphosphate (AMP-PNP; 0.2 mM). 4. Diazoxide (0.3 mM) strongly increased channel activity in the presence of ATP (0.1 mM) or GDP (0.03 mM), but was ineffective in the presence of AMP-PNP (0.1 mM). In the absence of cytosolic nucleotides diazoxide even decreased channel activity. 5. In the presence of 0.1 mM ATP, diazoxide activated KATP-channels half-maximally at 38 microM. 6. When KATP-channel activity was inhibited by 0.1 mM ATP, (-)-pinacidil (0.5 mM) elicited a slight activation of KATP-channels in caudate nucleus, whereas (+)-pinacidil (0.5 mM) and lemakalim (0.3 mM) were ineffective. 7. Since our data indicate similar control by drugs and nucleotides of KATP-channels in the somata of spiny neurones and pancreatic beta-cells, we conclude that the high affinity sulphonylurea receptors of these tissues are probably closely related.

Topographical organization of projections from the entorhinal cortex to the striatum of the rat

The efferent projections of the entorhinal cortex to the striatum were studied with retrograde (horseradish peroxidase–wheat germ agglutinin) and anterograde (biocytin and biotinylated dextran amine) tracing methods. The bulk of the entorhinal cortical fibres were found to project to the nucleus accumbens in the ventral striatum, but the caudate–putamen is only sparsely and diffusely innervated, rostrally, along its dorsal and medial borders. Fibres arising from neurons in the lateral entorhinal cortex project throughout the rostrocaudal extent of the nucleus accumbens but are most abundant in the core and lateral shell of that nucleus. The rostral neurons of the medial entorhinal cortex were found to project sparsely to the striatum, whereas caudal neurons provide a dense input to the rostral one-third of the nucleus accumbens, especially to the rostral pole, where they concentrate more in the core than in the shell. Contralateral entorhinal projections, which are very sparse, were found in the same parts of the nucleus accumbens and the caudate–putamen as the ipsilateral terminal fields.The present observations that entorhinal inputs to the nucleus accumbens are regionally aligned suggest that disruption of these connections could produce site-specific deficits with, presumably, specific behavioural consequences.

The embryonic cerebellum contains topographic cues that guide developing inferior olivary axons.

The formation of the olivocerebellar projection is supposed to be regulated by positional information shared between pre- and postsynaptic neurons. However, experimental evidence to support this hypothesis is missing. In the chick, caudal neurons in the inferior olive project to the anterior cerebellum and rostral ones to the posterior cerebellum. We here report in vitro experiments that strongly support the existence of anteroposterior polarity cues in the embryonic cerebellum. We developed an in vitro system that was easily accessible to experimental manipulations. Large hindbrain explants of E7.5-E8 chick embryos, containing the cerebellum and its attached brainstem, were plated and studied using axonal tracing methods. In these cultures, we have shown that the normal anteroposterior topography of the olivocerebellar projection was acquired, even when the cerebellar lamella was detached from the brainstem and placed again in its original position. We also found that, following various experimental rotations of the anteroposterior axis of the cerebellum, the rostromedian olivary neurons still project to the posterior vermis and the caudolateral neurons to the anterior vermis, that now have inverted locations. Thus, the rotation of the target region results in the rotation of the projection. In addition, we have shown that the formation of the projection map could be due to the inability of rostromedian inferior olivary axons to grow in the anterior cerebellum. All these experiments strongly indicate that olivocerebellar fibers recognize within their target region polarity cues that organize their anteroposterior topography, and we suggest that Purkinje cells might carry these cues.

Medullary pathways mediating depressor responses from Na(+)-sensitive sites in nucleus of the solitary tract.

Two series of experiments were done in male Wistar rats to investigate the medullary pathways that mediate the depressor responses from sodium-sensitive sites in the nucleus of the solitary tract (NTS). In the first series, the anterograde tract tracer Phaseolus vulgaris leucoagglutinin (PHA-L) was iontophoresed unilaterally at sites in the NTS at which microinjections (20 nl) of a 154-175 mM NaCl solution elicited depressor responses. PHA-L injection sites were found to be localized within the medial subnucleus of the NTS (Sm). In the medulla, PHA-L-labeled fibers and presumptive terminal boutons were observed bilaterally, but with an ipsilateral predominance, throughout the rostrocaudal extent of the NTS the dorsal motor nucleus of the vagus, area postrema, the ventrolateral medulla (VLM), and nucleus ambiguus. The pontine region, containing the A5 catecholaminergic cell group and the parabrachial nucleus, also received projections from Sm. In the second series of experiments, the effect of blocking synaptic transmission in VLM with cobalt chloride (CoCl2; 5 mM, 100 nl) on the cardiovascular response elicited by microinjection (20 nl) of hypertonic saline (154-175 mM) into the ipsilateral Sm was investigated in the alpha-chloralose-anesthetized, paralyzed, and artificially ventilated rat. Microinjection of CoCl2 into VLM, at sites shown in the previous study to receive efferent projections from Sm, significantly attenuated the depressor (60%) and bradycardic (80%) responses to stimulation of Sm. These data indicate that the sodium-sensitive region of the caudal Sm innervates VLM neurons and suggest that these VLM neurons are involved in mediating the depressor and bradycardic responses elicited by changes in the extracellular concentration of sodium.

P-505 - Effects of CS-722, a new central muscle relaxant, on caudate nucleus neurons receiving inputs from substantia nigra

P-505 - Effects of CS-722, a new central muscle relaxant, on caudate nucleus neurons receiving inputs from substantia nigra

Activity change of cat caudate neurons related to the learning of memory-guided saccade task

Activity change of cat caudate neurons related to the learning of memory-guided saccade task

2220 Activity change of cat caudate neurons related to the learning of memory-guided saccade task

2220 Activity change of cat caudate neurons related to the learning of memory-guided saccade task

Visual responses of monkey caudate neurons depend on reward expectancy

Three video-formatted experiments investigated the categorization of ‘above’ and ‘below’ spatial relations in baboons (Papio papio). Using an identity matching-to-sample task, six baboons correctly matched line–dot stimuli based on the ‘above’ or ‘below’ location of the dot relative to the line (Experiment 1). Positive transfer of performance was then observed when the line–dot distance depicted in the sample stimulus differed from that of the two comparison stimuli (Experiment 2). Using a go/nogo procedure, two baboons were further trained to discriminate whether a ‘B’ character was displayed ‘above’ or ‘below’ a ‘3’ character (Experiment 3). After training, a positive transfer of performance was observed with the same type of stimuli depicted in different type fonts. Altogether, these results suggest that baboons may form conceptual representations of ‘above’ and ‘below’ spatial relations, and categorize visual forms on that basis.

The Eph Kinase Ligand AL-1 Is Expressed by Rostral Muscles and Inhibits Outgrowth from Caudal Neurons

In the peripheral nervous system, neurons derived from specific rostrocaudal levels of the neuraxis selectively synapse on targets that arise from corresponding body positions. To identify molecules involved in such position-dependent connectivity, we used subtractive hybridization to isolate genes selectively expressed in rostral or caudal skeletal muscle. One mRNA that was more abundant in neck than in hindlimb muscles encoded the mouse ortholog of human AL-1 and chick RAGS, membrane-associated ligands of Eph tyrosine kinases that have recently been implicated in cortical axon fasciculation and retinotectal connectivity, respectively. We show here that mouse AL-1 is expressed in discrete regions of the central and peripheral nervous systems and in a subset of developing skeletal muscles. The abundance of AL-1 RNA in immortalized myogenic cell lines derived from rostral muscles is higher than in caudally derived lines, suggesting that levels are heritably maintained. Growth of neurites from cultured sensory ganglia and spinal cords is specifically inhibited by cells expressing AL-1, suggesting that this molecule could serve to guide peripheral axons. The inhibitory effects of AL-1 are position dependent, such that axons derived from caudal (lumbar) ganglia are more affected than those derived from rostral (cervical) ganglia. Together, these results support the notion that Eph kinases and their ligands regulate topographically appropriate neural connectivity in the peripheral nervous system, as well as in the central nervous system.

Differential Alteration of Neuronal and Cardiovascular Responses to Adenosine Microinjected Into the Nucleus Tractus Solitarius of Spontaneously Hypertensive Rats

We previously reported that adenosine elicited site-dependent neuronal and cardiovascular responses in two subareas of the nucleus tractus solitarius (NTS) of normotensive rats. Pressor and tachycardic responses were obtained from the rostral NTS (adenosine pressor system), and depressor and bradycardic responses were obtained from the caudal NTS (adenosine depressor system). In both areas, adenosine inhibited the firing rate of barosensitive neurons. The present study investigated whether spontaneously hypertensive rats (SHR) exhibit abnormal neuronal and cardiovascular responses mediated by the adenosine pressor and depressor systems within the NTS. Male SHR and Wistar-Kyoto rats (WKY) were anesthesized with urethane and prepared for blood pressure and heart rate recording, stereotaxic microinjection of adenosine into the NTS, and extracellular recording of single-unit neuronal activity of NTS neurons. Chemical identification of the targeted neuronal pool was made by L-glutamate (5 nmol) and confirmed by histology. SHR exhibited significantly higher mean arterial pressure and firing rate of caudal NTS neurons (45.0 +/- 4.5 versus 27.3 +/- 4.7 spikes per 2.5 seconds, P <.05) but similar heart rate and neuronal firing rate of rostral NTS neurons compared with WKY. Adenosine (0.1, 1, and 10 nmol) elicited dose-related neuronal and cardiovascular responses in both strains. However, SHR exhibited differential alterations in both adenosine systems. Compared with WKY, SHR exhibited attenuated pressor, tachycardic, and neuronal responses mediated by the adenosine pressor system and exaggerated depressor, bradycardic, and neuronal responses mediated by the adenosine depressor system. In both strains, the responses elicited by adenosine were virtually abolished by theophylline (10 mg/kg IV), suggesting that these responses were mediated by adenosine receptors in the NTS. Furthermore, the theophylline-evoked increase in blood pressure was twofold higher in SHR (15.0 +/- 1.7 versus 6.9 +/- 1.5 mm Hg, P <.05); larger but nonsignificant increases in heart rate and neuronal firing rate also were evident in SHR compared with WKY. These findings suggest differential alterations in adenosine pressor and depressor systems in the NTS of SHR, which may be implicated in the pathophysiology of this model of hypertension.

Tilt responses of neurons in the caudal descending nucleus of the decerebrate cat: influence of the caudal cerebellar vermis and of neck receptors.

1. In decerebrate cats with intact cerebellums, we studied the responses of neurons in the caudal areas of the vestibular nuclei to natural vestibular stimulation in vertical planes and to neck rotation. The activity of most neurons was recorded in the caudal half of the descending nucleus. 2. One goal of our experiments was to compare the dynamic and spatial properties of responses to sinusoidal vestibular stimulation with those seen in previous experiments in which the caudal cerebellar vermis, including the nodulus and uvula, was removed. This part of the cerebellum receives vestibular input and projects to the caudal areas of the vestibular nuclei, suggesting that it could influence responses to stimulation of the labyrinth. 3. As in our previous experiments, most neurons could be classified as receiving predominant input either from the otoliths or from one vertical semicircular canal. When mean gain and phase and response vector orientations were compared, there were no obvious differences between the behavior of neurons in the partially decerebellate preparation and the one with the cerebellum intact, demonstrating that in the decerebrate cat the nodulus and uvula have little or no influence on the processing of vertical vestibular input in this region of the vestibular nuclei. 4. Only 23 of 74 (31%) of neurons tested responded to neck rotation. This contrasts with the much larger fractions that respond to this stimulus in Deiters' nucleus and in the rostral descending nucleus. We also recorded from neurons near the vestibular nuclei, mainly in the external cuneate nucleus. All of them (9 of 9) responded to neck rotation. 5. Responses to neck rotation also differed in their dynamics from those found more rostrally in the vestibular nuclei. Dynamics of more rostral neurons resemble those of neck muscle spindles, as do those of external cuneate neurons. The dynamics of caudal vestibular neurons, on the other hand, have a steeper gain slope and more advanced phases than do those of neurons in the more rostral vestibular nuclei. This suggests the possibility of involvement of additional receptors in the production of these responses. 6. In the more rostral vestibular nuclei, responses to vestibular and neck rotation are most often antagonistic, so that head rotation results in little or no response. This is not the case in the caudal areas of the vestibular nuclei, where less than half the neurons tested displayed antagonistic behavior. Further experiments are required to put the neck projection to the caudal vestibular nuclei in a functional context.