Biomedical subjects

N C Owens

Publications and source records attributed to N C Owens.

10 recordsLinked to original sources

PubMed2005

Right atrial stretch activates neurons in autonomic brain regions that project to the rostral ventrolateral medulla in the rat.

Activation of the cardiac mechanoreceptors results in changes in sympathetic nerve activity and plays an important role in the responses elicited by elevated blood volume. Stimulation of the reflex influences several key autonomic regions, namely the paraventricular nucleus (PVN), the nucleus of the tractus solitarius (NTS) and the caudal ventrolateral medulla (CVLM). Neurons in these regions project directly to the rostral ventrolateral medulla (RVLM), a critical region in the generation of sympathetic vasomotor tone. The aim of the present experiments was to determine whether neurons in the PVN, NTS and CVLM that are activated by cardiac mechanoreceptor stimulation also project to the RVLM. Animals were prepared, under general anesthesia, by microinjection of a retrogradely transported tracer into the pressor region of the RVLM, and the placement of a balloon-tipped cannula at the junction of the right atrium and the superior vena cava. On the experimental day, in conscious rats, the balloon was inflated to stimulate cardiac mechanoreceptors (n = 9), or left uninflated (control, n = 8). Compared with controls, there was a significantly increased number of Fos-immunoreactive neurons (a marker of activation) in both the PVN (2.5-fold) and NTS (two-fold), but this was not seen in the CVLM. Compared with controls, a significant number of the neurons in the PVN (8%) and NTS (4.0%) that projected to the RVLM were activated. The data suggest that subgroups of RVLM-projecting neurons located in the PVN and NTS are involved in the central reflex pathway activated by cardiac mechanoreceptor stimulation.

Afferent Pathways↗

PubMed2002

Thermoregulatory control of sympathetic fibres supplying the rat's tail.

We investigated the thermoregulatory responses of sympathetic fibres supplying the tail in urethane-anaesthetised rats. When skin and rectal temperatures were kept above 39 degrees C, tail sympathetic fibre activity was low or absent. When the trunk skin was cooled episodically by 2-7 degrees C by a water jacket, tail sympathetic activity increased in a graded fashion below a threshold skin temperature of 37.8 +/- 0.6 degrees C, whether or not core (rectal) temperature changed. Repeated cooling episodes lowered body core temperature by 1.3-3.1 degrees C, and this independently activated tail sympathetic fibre activity, in a graded fashion, below a threshold rectal temperature of 38.4 +/- 0.2 degrees C. Tail blood flow showed corresponding graded vasoconstrictor responses to skin and core cooling, albeit over a limited range. Tail sympathetic activity was more sensitive to core than to trunk skin cooling by a factor that varied widely (24-fold) between animals. Combined skin and core cooling gave additive or facilitatory responses near threshold but occlusive interactions with stronger stimuli. Unilateral warming of the preoptic area reversibly inhibited tail sympathetic activity. This was true for activity generated by either skin or core cooling. Single tail sympathetic units behaved homogeneously. Their sensitivity to trunk skin cooling was 0.3 +/- 0.08 spikes s(-1) degrees C(-1) and to core cooling was 2.2 +/- 0.5 spikes s(-1) degrees C(-1). Their maximum sustained firing rate in the cold was 1.82 +/- 0.35 spikes s(-1).

Adrenergic Fibers↗

PubMed2001

Regional haemodynamic responses to activation of the medial prefrontal cortex depressor region.

Electrical or chemical stimulation of the medial prefrontal cortex (MPFC) produces depressor and sympathoinhibitory responses. To characterise the MPFC depressor response more fully, we determined the regional haemodynamic changes which occurred in response to stimulation of the MPFC. In halothane-anaesthetised rats, we recorded arterial blood pressure and renal, superior mesenteric, and iliac arterial vascular conductance using miniaturised Doppler flow probes. Electrical stimulation of the MPFC (50-100 microA) was used to map the location of the depressor region. Increases in vascular conductance (or increases in blood flow) were recorded from the renal (+2.3+/-0.5 kHz/mmHgx10(3)), mesenteric (+4.4+/-0.4 kHz/mmHgx10(3)), and iliac (+8.3+/-1.0 kHz/mmHgx10(3)) vascular beds in response to stimulation of the MPFC depressor region coinciding with the ventral infralimbic (IL) and dorsal peduncular (DP) cortical areas. Similar responses were obtained after microinjection of the chemical excitant L-glutamate (n=3, 100 nl, 100 mM), indicating that the responses were due to excitation of cell bodies and not due to axons traversing the area. Administration of the nitric oxide synthesis inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 25 micromol/kg, i.v., n=5) significantly reduced the MPFC depressor response (51%, 12.5+/-1.2 to 6.1+/-2.5 mmHg). The increases in conductance in the hindquarter and mesenteric vascular beds were significantly reduced after L-NAME treatment (mesenteric by 77%, iliac by 70%), but there was no significant reduction of renal flow (35%). These observations indicate that the depressor region of the MPFC is localised to ventral regions (IL and DP) and that the depressor response is mediated by increased conductance in the hindquarters and mesenteric vascular beds. Furthermore, the depressor response may be mediated, in part, by release of nitric oxide in these vascular beds.

Animals↗

PubMed2001

Cold-activated raphé-spinal neurons in rats.

1. In a search for sympathetic premotor neurons subserving thermoregulatory functions, medullary raphé-spinal neurons were studied in urethane-anaesthetized, artificially ventilated, paralysed rats. Extracellular unit recordings were made from a region previously shown to drive the sympathetic supplies to tail vessels and brown adipose tissue. Neurons that were antidromically activated by stimulation across the intermediate region of the upper lumbar cord (the origin of the tail sympathetic outflow) were selected for study. 2. Non-noxious cooling stimuli were delivered to the animal's shaved trunk by circulating cold instead of warm water through a water jacket. Cooling increased the activity of 21 out of 76 raphé-spinal neurons by 1.0 +/- 0.2 spikes x s(-1) degrees C(-1) for falls in skin temperature of 3-5 degrees C below a threshold of 35.0 +/- 0.6 degrees C. Their responses followed skin temperature in a graded manner, and did so whether or not there was any change in core (rectal) temperature. 3. Indirect observations suggested that seven of the neurons that were activated by skin cooling were also activated by falls in core temperature (by 2.1 +/- 0.7 spikes x s(-1) x degrees C(-1) below a threshold of 36.1 +/- 0.7 degrees C), while the remainder were unaffected by core cooling. 4. An additional 7/76 raphé-spinal neurons showed evidence of inhibition (activity reduced by 2.1 +/- 0.5 spikes x s(-1) x degrees C(-1)) when the trunk skin was cooled. 5. Cold-activated raphé-spinal neurons were found in the nuclei raphé magnus and pallidus, centred at the level of the caudal part of the facial nucleus. Their spinal axons conducted at velocities between 3.4 and 29 m x s(-1) (median 6.8). 6. Drug-induced rises in arterial pressure partially inhibited the discharge of 6/14 cold-activated raphé-spinal neurons. Weak-to-moderate cardiac modulation (10-70 %) was present in arterial pulse-triggered histograms of the activity of 11/21 cold-activated raphé-spinal neurons, and 6/6 showed evidence of ventilatory modulation (two strongly, four weakly) in pump-triggered histograms. 7. Raphé-spinal neurons responded to cooling in the absence of any change in the electroencephalogram pattern (6/6 neurons). 8. Most cold-activated raphé-spinal neurons responded to noxious tail pinch (13/21 inhibited, 6/21 excited), as did most thermally unresponsive raphé-spinal cells in the same region (19/41 excited, 9/41 inhibited). 9. It is suggested that these cold-activated raphé-spinal neurons may constitute a premotor pathway that drives sympathetically mediated cold defences, such as cutaneous vasoconstriction or thermogenesis. The data are consistent with the hypothesis that a brainstem reflex, with additional descending input signalling body core temperature, may mediate autonomic responses to environmental cooling.

Animals↗

PubMed2000

Medial prefrontal depressor response: involvement of the rostral and caudal ventrolateral medulla in the rat.

The importance of neurones of the caudal and rostral ventrolateral medulla (CVLM and RVLM, respectively) in mediation of the medial prefrontal cortex depressor response was studied in halothane-anaesthetised rats. Blockade of GABA(A) receptors in the RVLM produced by microinjection of bicuculline (50 nl, 2 mM, n = 6) resulted in reversal of the depressor (-9.5 +/- 1.2 mm Hg) and lumbar sympathetic (-6.5 +/- 5.7 units) responses to pressor (+7.8 +/- 3.5 mm Hg) and sympathoexcitatory (+19.3 +/- 12.5 units) responses and simultaneous blockade of baroreceptor reflex-mediated sympathoinhibition. Baroreflex blockade was reflected by a significant reduction in the gain (slope of the blood pressure vs. lumbar sympathetic nerve discharge regression line) of the reflex. Microinjection of the excitatory amino acid antagonist kynurenic acid (100 nl, 50 mM, n = 6) into the CVLM blocked the baroreflex and significantly reduced the depressor (-9.6 +/- 0.4 to -6.9 +/- 0.6 mm Hg) and lumbar sympathetic (-4.0 +/- 2.1 to 2.9 +/- 1.9 units) responses to medial prefrontal cortex stimulation. These results support the hypothesis that the medial prefrontal cortex depressor response is mediated by a pathway which converges at the level of the RVLM and which is only partly dependent on an excitatory input to caudal ventrolateral medullary neurones.

Animals↗

PubMed1999

Medial prefrontal cortex depressor response: role of the solitary tract nucleus in the rat.

The depressor response elicited by unilateral low intensity electrical stimulation of the rat ventral medial prefrontal cortex may be mediated by a connection with the solitary tract nucleus. We tested this hypothesis by (i) examining the influence of medial prefrontal cortex stimulation on the induction of Fos-like immunoreactivity in neurons in the medulla oblongata, and (ii) by testing the effect of inhibition of solitary tract nucleus neurons on the medial prefrontal cortex stimulation-evoked depressor response. Depressor responses (>10 mmHg) were elicited by electrical stimulation of the medial prefrontal cortex every minute for 1 h ('Stimulated' group). Control animals were treated identically but did not receive electrical stimulation ('Unstimulated' group). Neurons exhibiting Fos-like immunoreactivity were abundant at the stimulation site which included the infralimbic area, and dorsal peduncular cortex. Medullary Fos-like immunoreactivity observed in the 'Stimulated' and 'Unstimulated' groups exceeded levels observed in untreated rats and was detected in the rostral, caudal and intermediate areas of the ventrolateral medulla, and the commissural, intermediate, medial and lateral regions of the solitary tract nucleus, as well as the medial vestibular nucleus, and the dorsal motor nucleus of the vagus. The number of neurons displaying Fos-like immunoreactivity in the ipsilateral solitary tract nucleus and caudal ventrolateral medulla of the 'Stimulated' group was found to be significantly elevated compared to the contralateral side (P<0.05), and the 'Unstimulated' group bilaterally. Inhibition of solitary tract nucleus neurons using bilateral injections of the GABA(A) receptor agonist muscimol (44 pmol/25 nl) inhibited the sympathetic vasomotor baroreflex and attenuated the depressor and sympathoinhibitory response to medial prefrontal cortex stimulation by 62% and 65%, respectively. These findings suggest that the projection from the medial prefrontal cortex to the solitary tract nucleus is excitatory and support the hypothesis that the depressor response elicited by medial prefrontal cortex stimulation is mediated, in part, by a cortico-solitary projection which activates the intramedullary baroreflex pathway.

Animals↗

PubMed1998

Cortical modulation of the cardiovascular system.

Cortical modulation of central cardiovascular control mechanisms has been recognized for many decades. However, it is only recently that the mechanisms underlying cortical influences on circulatory function have been systematically examined. This review considers the view that certain regions of the cerebral cortex, including the medial prefrontal cortex (MPFC) and insular cortex (IC), participate in specific aspects of central circulatory control. Anatomical investigations indicate that these cortical areas are connected with hypothalamic, midbrain, pontine and medullary brain regions involved in cardiovascular control. Lesions of the MPFC and IC have demonstrated modulation of the activity of cardiovascular reflexes such as the baroreceptor heart rate reflex and involvement in conditioned cardiovascular responses. Electrophysiological studies have provided evidence that cortical regions are able to influence premotor sympathoexcitatory vasomotor neurons within the rostral ventrolateral medulla and subsequently alter sympathetic vasomotor tone. Cortical regions such as the IC receive visceral sensory information arising from baroreceptors and chemoreceptors within the cardiovascular system. In contrast, the MPFC receives afferents predominantly from limbic sources, although its outputs include structures associated with central sympathetic vasomotor control. Cortical modulation of circulatory function has been demonstrated in man and may underlie the cardiovascular components of a number of conditions. It is suggested that cortical areas involved in visceral sensory or visceral motor processes associated with circulatory function may be involved in generation of patterns of cardiovascular responses specific for certain behaviours.

Afferent Pathways↗

PubMed1996

An electrophysiological study of the medial prefrontal cortical projection to the nucleus of the solitary tract in rat.

The medial prefrontal cortex (MPFC) has been described as a "visceromotor" cortical area, since autonomic effects such as depressor responses may be elicited from this area. The central circuitry which mediates these depressor responses may include a projection from the MPFC to the nucleus of the solitary tract (NTS). Neurones were recorded extracellularly in the MPFC and were tested for antidromic (AD) activation from the NTS. These were all tested for (1) constant spike latency, (2) ability to follow high-frequency stimulation to more than 200 Hz, and (3) where possible, collision of stimulation-evoked spike with spontaneous spike or spikes evoked by iontophoretic application of glutamate. Of the 34 cells studied, all had constant AD latency (30 +/- 1 ms, range 16-46 ms); they followed high-frequency stimulation up to 354 +/- 19 Hz, and only seven cells were spontaneously active (range 1-19 spikes/s). The threshold stimulation intensity for AD activation was 102 +/- 9 microA (n = 34, range 8-200 microA). Depth-threshold curves (n = 7) showed minimum-threshold AD activation currents that corresponded to the dorsal and ventral subdivisions of the NTS. Small shifts in AD latency were found in the depth-threshold curves, suggesting axonal branching. Analysis of recording sites showed that NTS-projecting MPFC neurones were predominantly found in the infralimbic and ventral prelimbic regions of the MPFC. These findings indicate that there is a population of neurones in the MPFC that projects to, and probably terminates within, the NTS. It is possible that this projection may, in part, mediate the cardiovascular response to MPFC stimulation.

Animals↗

PubMed1995

A simple and reliable method for construction of parallel multibarrel microelectrodes.

A modification to the method of construction of parallel or "piggy-back" electrodes for extracellular single-unit recording combined with iontophoresis is described that facilitates the alignment of the two components of the array. The method involves the use of an orthogonal viewing device (a pair of mirrors mounted symmetrically at 45 degrees to the horizontal), which produces a pair of virtual images of the electrode components that can be viewed with a microscope. A slight displacement between the electrodes is easily detected as an uneven separation between the electrode images. The positions of the electrode components are adjusted until there is no visible separation of the electrodes or their virtual images.

Animals↗

PubMedDate not supplied

Supramedullary modulation of sympathetic vasomotor function.

1. Supramedullary structures including the ventral medial prefrontal cortex (MPFC) and the midbrain cuneiform nucleus (CnF) project directly and indirectly to premotor sympatho-excitatory neurons of the rostral ventrolateral medulla (RVLM) that are critically involved in the generation of sympathetic vasomotor tone. 2. Electrophysiological studies have demonstrated that activation of depressor sites within the MPFC is associated with splanchnic sympathetic vasomotor inhibition and inhibition of the activity of RVLM sympathoexcitatory neurons. 3. Antidromic mapping and anatomical studies support the notion that a relay in the nucleus tractus solitarius is involved in the cardiovascular response to MPFC stimulation. 4. The midbrain CnF, which lies adjacent to the midbrain periaqueductal grey, is a sympathoexcitatory region of the midbrain reticular formation. Sympathoexcitatory responses evoked from the CnF are associated with short-latency excitation of RVLM neurons. 5. Cuneiform nucleus stimulation induces the expression of mRNA for the immediate early genes c-fos and NGFI-A in mid-brain, pontine and hypothalamic structures. 6. The MPFC and CnF are supramedullary structures with opposing modulatory influences on sympathetic vasomotor drive, whose roles in cardiovascular control mechanisms warrant further investigation.

Animals↗