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Biomedical subjects

A V Ferguson

Publications and source records attributed to A V Ferguson.

At least 91 records · Page 5Linked to original sources

Paraventricular nucleus stimulation causes gastroduodenal mucosal necrosis in the rat.

The effects of stimulation in the paraventricular nucleus (PVN) of the hypothalamus on the development of gastrointestinal ulceration have been examined in urethan-anesthetized male Sprague-Dawley rats. Electrical stimulation (200 microA, 60 Hz, 100-microseconds pulse width) in the PVN was performed for 1 h, after which samples of the stomach and duodenum were fixed for subsequent histological assessment of damage. Such damage was scored, blindly, on a 0 (normal) to 3 (severe) scale. Stimulation in the PVN resulted in necrosis and hemorrhage in both the stomach (mean damage score of 1.8 +/- 0.3) and duodenum (1.7 +/- 0.4). In contrast, similar stimulation in regions immediately adjacent to the PVN was found to be without significant effect on the stomach (0.3 +/- 0.1) or duodenum (0.6 +/- 0.2). In a second series of studies PVN stimulation following bilateral vagotomy resulted in damage scores (stomach: 0.2 +/- 0.1; duodenum: 0.1 +/- 0.1) that were significantly reduced compared with the PVN-stimulated vagal-intact group (P less than 0.05) but were not significantly different from the group stimulated in regions outside the PVN (P greater than 0.1). These data suggest an important role for PVN efferents influencing medullary vagal preganglionic neurons in the development of acute gastroduodenal ulceration.

Animals↗

Systemic angiotensin acts at the subfornical organ to control the activity of paraventricular nucleus neurons with identified projections to the median eminence.

The present studies were carried out to investigate the mechanisms through which systemic angiotensin II (AII) acts within the central nervous system to influence the release of anterior pituitary hormones in the Sprague-Dawley rat. In particular, these studies have examined the role of the subfornical organ (SFO) as an essential structure mediating these responses. Extracellular single-unit recordings were obtained from 199 paraventricular nucleus (PVN) neurons antidromically identified as projecting to the median eminence. Different groups of these neurons were tested for the effects of either electrical stimulation in the SFO (n = 87) or systemic AII administration in intact (n = 49) and SFO-lesioned (n = 25) animals. Of cells tested with SFO stimulation 45% were excited, 16% inhibited, and the remainder unaffected. Neurons which were excited were primarily located just medial to the magnocellular neurons in the region where the majority of corticotropin-releasing hormone immunoreactive cells are found. In contrast, inhibitory responses were observed in cells located in the dorsal medial PVN, a region containing thyrotropin-releasing hormone, somatostatin, and dopamine PVN-median eminence neurons. Following systemic AII 42% of cells tested showed increased activity specific to the effects of this peptide, and 20% showed alterations in activity associated with the cardiovascular changes induced by AII. In contrast, following SFO lesion only 8% of neurons tested showed specific excitatory responses to AII. In order to test the hypothesis that systemic AII may activate this excitatory SFO to PVN pathway, a further group of 35 neurons were tested with both SFO stimulation and AII.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Subfornical organ connections with septal neurons projecting to the median eminence.

We have examined the effect of electrical stimulation in the subfornical organ (SFO) on the activity of neurons in the medial septum and diagonal band of Broca (MS-DBB) which project to the median eminence in the rat. Previous studies have suggested that septal neurons with such projections are luteinizing hormone releasing hormone neurons. Extracellular single-unit recordings were obtained from 69 neurons in the MS-DBB which were antidromically identified as projecting to the median eminence. Electrical stimulation (100-400 microA) in the SFO resulted in a relatively short-latency (22.8 +/- 0.8 ms), short-duration (9.2 +/- 0.8 ms) activation of 85% of 41 antidromically identified MS-DBB neurons tested. One neuron was inhibited by SFO stimulation, while the remaining 12% were unaffected. Stimulation in nearby regions, including the hippocampal commissure and paraventricular nucleus of the thalamus, failed to elicit a similar excitatory response from 19 identified MS-DBB neurons. These results identify a neuronal pathway between the SFO and septal neurons which project to the median eminence, supporting a possible role for the SFO in the control of luteinizing hormone releasing hormone release and hence gonadotropin secretion.

Action Potentials↗

Analysis of the role of angiotensin II in mediation of adrenocorticotropin secretion.

It has been suggested that ACTH secretion in response to selected stimuli may be modulated by angiotensin II (AII) via direct action at the level of the corticotrope or through central actions to facilitate CRF secretion into the hypophysial-portal circulation. These hypotheses were evaluated in the present series of experiments. Our failure to observe a significant portal to peripheral plasma immunoreactive (ir) AII gradient suggested that AII does not act as a physiologically significant ACTH secretagogue at the level of the corticotrope. Central administration of synthetic AII evoked a modest dose-related stimulation of hypothalamic irCRF secretion into the portal circulation, which was reversed by the AII receptor antagonist saralasin. Activation of a known AII-positive neuronal pathway projecting from the subfornical organ (SFO) to the hypothalamic paraventricular nuclei resulted in an elevation of hypophysial-portal plasma irCRF levels and increased circulating ACTH. Pretreatment with saralasin prevented SFO stimulation-induced irCRF secretion. These observations suggest that central AII-containing pathways may participate in mediation of ACTH secretion in response to hypovolemia or hyperosmolality by facilitating irCRF secretion. Involvement of the SFO, a circumventricular organ, in this circuit is intriguing as it provides a means of monitoring peripheral irAII concentration and then converting this humoral signal into a neural signal distributed to regions regulating drinking behavior, neurohypophysial AVP secretion, and activation of the hypothalamic-pituitary-adrenal axis.

Adrenocorticotropic Hormone↗

Activation of subfornical organ efferents stimulates oxytocin secretion in the rat.

The effects of activation of subfornical organ (SFO) efferents on plasma oxytocin concentrations were examined in conscious freely moving male Sprague-Dawley rats. Blood samples were obtained through chronically implanted atrial catheters and SFO efferents were activated electrically using chronically implanted bipolar stimulating electrodes. Hormone concentrations were measured by radioimmunoassay, and experimental animals were assigned to one of 3 experimental groups according to histologically verified anatomical locations of stimulating electrodes in either the SFO, the hippocampal commissure (HC), or the medial septum (MS). Electrical stimulation in the SFO resulted in increased plasma concentrations of oxytocin from control values of 2.54 +/- 0.9 pg/ml, to a post-stimulation level of 65.6 +/- 27.0 pg/ml. In contrast, stimulation in immediately adjacent structures including HC and MS was found to be without effect on plasma concentrations of oxytocin. These studies provide the first definitive evidence that SFO efferents may play a significant role in controlling the secretion of oxytocin from the posterior pituitary.

Animals↗

Electrical stimulation in subfornical organ increases plasma vasopressin concentrations in the conscious rat.

Electrical stimulation in the subfornical organ (SFO) of conscious freely moving rats was found to increase plasma vasopressin concentrations from control values of 1.43 +/- 0.32 to poststimulation values of 22.32 +/- 4.9 pg/ml (P less than 0.01). Similar stimulation in immediately adjacent brain regions including the medial septum and hippocampal commissure caused no significant changes in plasma concentrations of this peptide hormone. These data indicate that activation of SFO neurons in conscious rats causes increased release of vasopressin from the posterior pituitary. Such data corroborate previous electrophysiological findings demonstrating that in anesthetized animals electrical stimulation in SFO results in increased excitability of antidromically identified vasopressin-secreting neurons in the supraoptic and paraventricular nuclei of the hypothalamus.

Animals↗

Systemic angiotensin acts at subfornical organ to facilitate activity of neurohypophysial neurons.

Extracellular single unit recordings were obtained to investigate the effects of systemic administration of angiotensin II (ANG II) on the excitability of antidromically identified neurohypophysial neurons in the rat. Records were obtained from 89 oxytocin- or vasopressin-secreting neurons in the hypothalamic supraoptic or paraventricular nuclei. Increased excitability in response to ANG II was observed in 83% of putative vasopressin- and 75% of putative oxytocin-secreting neurons tested in intact animals. Lesion studies to identify the central nervous system site of action for such peripherally administered ANG II showed that, after electrolytic lesion of the rostral subfornical organ (SFO), neurohypophysial neurons demonstrated no increase in excitability in response to this peptide. In an attempt to correlate the synaptic events through which activation of SFO neurons may result in facilitated excitability of neurohypophysial cells, 19 cells were tested with both systemic ANG II and electrical stimulation in the SFO. These studies demonstrated that all cells which showed long-duration increases in excitability in response to electrical stimulation of SFO were also activated by systemic ANG II. It is concluded that the SFO is an essential central nervous system structure in eliciting increases in the excitability of both oxytocin- and vasopressin-secreting neurons in response to systemic ANG II. These effects may involve the activation of SFO efferents that evoke long-duration post-synaptic changes in neurohypophysial cell excitability.

Angiotensin II↗

Neurotransmitter effects on body temperature are modified with increasing age.

This study reports effects on body temperature, in two different age groups of Sprague Dawley rats, of intracerebroventricular (ICV) administration of prostaglandin E2, noradrenaline, serotonin, dopamine, and carbachol. Young animals (3-5 months) developed fevers in response to administration of prostaglandin E2 (+ 1.02 +/- 0.26 degrees C), while no significant changes in colonic temperature were observed in the older (15-18 months) group of rats. Noradrenaline (10.0 micrograms), caused a decrease in colonic temperature in the younger group of animals (-2.02 +/- 0.70 degrees C), but had no significant effects on the body temperature of the older group. Similarly, differences between the temperature responses of the young as compared with the older group of animals were observed following ICV administration of carbachol, dopamine and serotonin. These data suggest that the roles of these substances in the hypothalamic control of body temperature may be modified with increasing age.

Aging↗

Electrophysiology of the subfornical organ and its hypothalamic connections--an in-vivo study in the rat.

The connections of the subfornical organ to a defined population of hypothalamic neurons have been explored with extracellular recording methods in the rat. Electrical stimulation in the subfornical organ has a predominantly excitatory action on a majority of oxytocin and vasopressin-secreting neurosecretory neurons in the supraoptic and paraventricular nuclei. Subfornical organ stimulation also enhances the excitability of paraventricular nucleus neurons that project to the median eminence, and to the dorsomedial medulla. These observations provide initial evidence of functional connectivity of subfornical organ neurons with other hypothalamic cells that are engaged in central regulation of pituitary secretions and autonomic activities.

Animals↗

Subfornical organ and supraoptic nucleus connections with septal neurons in rats.

Extracellular single unit recordings obtained in pentobarbital-anesthetized male Sprague Dawley rats were utilized to examine the electrophysiology of connections of medial septum-diagonal band of Broca (MS-DBB) neurons with the subfornical organ (SFO), hippocampal commissure (HC), and supraoptic nucleus (SON). Of the 119/216 cells tested that demonstrated antidromic activation from SON, many (60%) were orthodromically excited by SFO stimulation, whereas most (68%) were unresponsive to stimulation in the adjacent HC. Separate populations of MS-DBB neurons that displayed antidromic activation from the SFO (11/140 cells tested) or HC (24/78 tested) were orthodromically excited by SON stimulation. Three cells were activated antidromically from both the SFO and SON. These observations reveal some possible interconnections between these three brain regions and point to the existence of an indirect pathway whereby the SFO can influence SON neurons through an influence on MS-DBB neurons.

Animals↗

Noradrenergic afferents facilitate the activity of tuberoinfundibular neurons of the hypothalamic paraventricular nucleus.

The role of ascending noradrenergic projections of medullary origin in regulating the activity of tuberoinfundibular neurons of the hypothalamic paraventricular nucleus (PVN) was examined in pentobarbital-anesthetized male Sprague-Dawley rats. Discrete electrical stimulation of either the A1 or the A2 noradrenaline cell group areas of the caudal medulla enhanced the probability of firing in a substantial proportion of antidromically identified tuberoinfundibular PVN cells tested. Notably, no inhibitory effects were observed. Destruction of the PVN noradrenergic terminal plexus by local application of the neurotoxin 6-hydroxydopamine 1 day prior to electrophysiological experiments abolished the effects of both A1 and A2 stimulation. These findings indicate that noradrenergic afferents can exert a facilitatory influence on the activity of a population of tuberoinfundibular PVN neurons, thus supporting earlier suggestions that central noradrenergic structures can enhance the release of certain anterior pituitary hormones.

Animals↗

Hypothalamic paraventricular nucleus lesions decrease pressor responses to subfornical organ stimulation.

Electrical stimulation of the subfornical organ (SFO) in urethane anesthetized male Sprague-Dawley rats was associated with intensity and frequency dependent increases in arterial blood pressure. Stimulation in the hypothalamic paraventricular nucleus (PVN) also evoked increases in arterial blood pressure. Electrolytic lesions of the PVN significantly reduced SFO induced pressor responses, suggesting that the PVN constitutes part of the efferent pathways through which SFO stimulation elicits increases in blood pressure.

Animals↗

Subfornical organ--supraoptic nucleus connections: an electrophysiologic study in the rat.

Extracellular recordings from antidromically-identified neurosecretory cells in the rat supraoptic nucleus (SON) indicate that electrical stimulation (1 Hz, 50 microseconds, 200 microA) in the subfornical organ (SFO) alters the excitability of 89% (n = 31) of phasically-active (putative vasopressin-secreting) and 94% (n = 16) of continuously-active (putative oxytocin-secreting) neurons; 45% of cells display a long latency (mean 80.2 +/- 20.5 ms, S.D.) prolonged (150-350 ms) increase in excitability; 26% of cells demonstrate a similar excitation, preceded by a brief decrease in firing at a latency of 30.5 +/- 13.1 ms; 15% of cells display only a depression in their activity, lasting up to 150 ms. Ninety percent of non-neurosecretory (i.e. non-antidromic) neurons (n = 19) within or above th SON also display orthodromic excitatory or inhibitory responses to SFO stimulation; however, these cells usually respond with shorter latencies, and none demonstrate the prolonged excitation seen among neurosecretory cells. With SON stimulation, antidromic activation observed from 6 of 18 SFO neurons (latency range of 12-27 ms) confirms a projection from SFO to the SON area. These data suggest a predominantly facilitatory influence of SFO neurons on the excitability of both vasopressinergic and oxytocinergic neurosecretory cells in the rat, thereby supporting a role for the SFO in body water balance.

Animals↗

Connections of hypothalamic paraventricular neurons with the dorsal medial thalamus and neurohypophysis: an electrophysiological study in the rat.

Connections between the hypothalamic paraventricular nucleus (PVN) and thalmic paraventricular nucleus ( PVT ) were examined using electrophysiological methods. Efferent projections of adjacent PVN cells were defined on the basis of antidromic activation from either PVT (n = 12) or neurohypophyseal (n = 38) stimulation; antidromic activation from both sites (n = 3) suggested that some PVN cells project both to the PVT and to the neurohypophysis. PVT stimulation evoked only weak orthodromic responses from 21% of PVN neurohypophyseal neurons, whereas short latency, high probability orthodromic responses were observed from 43% of PVN non-neurosecretory neurons. These data indicate reciprocal PVN- PVT connections and suggest that PVT afferents preferentially innervate non-neurosecretory PVN cells.

Animals↗

Changes in the hypothalamic mechanisms involved in the control of body temperature induced by the early thermal environment.

The experiments reported in this study were designed to investigate the influence of the early thermal environment on the functional properties of certain putative thermoregulatory neurotransmitters within the hypothalamus of the Sprague-Dawley rat. The effects on body temperature of serotonin, dopamine, carbachol, PGE2 and endotoxin when microinjected into the anterior hypothalamic/preoptic region of the brain have been examined in warm-reared, control and warm-acclimated animals. Serotonin and PGE2 are shown to have different effects on body temperature in warm-reared as compared to warm-acclimated and control animals. The thermoregulatory effects of intrahypothalamic dopamine are shown to be changed by the normal acclimation process, while carbachol and endotoxin have similar effects on the body temperature of all 3 groups of animals. These data suggest that the thermal environment may significantly affect the roles which specific neurotransmitters play in the control of body temperature.

Acclimatization↗

The afferent pathway for carotid body chemoreceptor input to the hypothalamic supraoptic nucleus in the rat.

The pathway for chemoreceptor input to hypothalamic supraoptic nuclei has been examined in anaesthetised lactating and non-lactating rats. In lactating rats, the increase in intramammary pressure following bilateral carotid occlusion, which is probably mainly due to vasopressin, was abolished by lesions in the septum, but not by lesions in more caudal regions of the hypothalamus. In non-lactating rats, electrophysiological experiments demonstrated that the input from carotid body chemoreceptors to phasically-discharging supraoptic neurones is ipsilateral only. The effects of chemoreceptor stimulation on the neurones can be mimicked by electrical stimulation within the medial preoptic area and anterior hypothalamus in a region medial and rostral to the supraoptic nuclei. Lesions within this region abolish the chemoreceptor input to the supraoptic nuclei, but leave the baroreceptor input intact. It is proposed that chemoreceptor afferents to the supraoptic nuclei pass in the lateral hypothalamus to the region of the septum where they turn medially and descent through the medial part of the rostral hypothalamus. The results are discussed in terms of the general role of the chemoreceptor reflex and, more specifically, with respect to the possible significance of vasopressin in the control of arterial blood pressure.

Afferent Pathways↗

CNS regulation of reproduction: peptidergic mechanisms.

The coordinated activities of several networks of peptidergic neurons contribute to the overall neural regulation of reproduction and associated behaviours. Key elements are rostral hypothalamic cells that synthesize and release LHRH from their median eminence nerve terminals, subject to modulation by a variety of endogenous transmitters and neuropeptides including VIP, CCK, opioids and somatostatin. In the CNS, LHRH may also participate in intercellular communication to facilitate the expression of estrogen-sensitive sexual behavior. Vasopressin and oxytocin also appear to modulate maternal and reproductive behavior. In addition, 'oxytocinergic' neurons recorded during lactation and milk ejection display unique bursting activity patterns deemed important for efficient release of hormone. However, endogenous opioid peptides appear able to dissociate this stimulus-secretion coupling mechanism, possibly through interference with a calcium sensitive component in nerve terminals.

Animals↗

Effect of cooling on supraoptic neurohypophysial neuronal activity and on urine flow in the rat.

The activity of antidromically identified supraoptic neurosecretory neurones was recorded in Sprague-Dawley rats under urethane or sodium pentobarbitone anaesthesia during cooling of the body with a cold pack. Of twelve phasic neurones studied during a complete cooling and rewarming cycle, six displayed an initial increase, followed by a depression in activity during the period of reduced body temperature. The remaining six phasic neurones did not alter their activity during cooling. Non-phasic neurohypophysial neurones displayed a reversible reduction (n = 8), or increase (n = 6) in activity during cooling, while seven neurones were unaffected by changes in body temperature. In four other anaesthetized Sprague-Dawley rats, urine flow was reduced by approximately 50% during cooling; this was followed by a diuresis after removal of the cold pack and return of body temperature to normal. The antidiuresis did not occur in homozygous Brattleboro rats which lack arginine vasopressin. The electrophysiological data from a proportion of the supraoptic neurohypophysial neurones correlate with the observed changes in urine flow.

Action Potentials↗