Students from a large Australian university use Twitter to identify difficult course concepts to review during face-to-face lectorial sessions.

Engaging undergraduate students in large classes is a constant challenge for many lecturers, as student participation and engagement can be limited. This is a concern since there is a positive correlation between increased engagement and student success. The lack of student feedback on content delivery prevents lecturers from identifying topics that would benefit students if reviewed. Implementing novel methods to engage the students in course content and create ways by which they can inform the lecturer of the difficult concepts is needed to increase student success. In the present study, we investigated the use of Twitter as a scalable approach to enhance engagement with course content and peer-to-peer interaction in a large course. In this pilot study, students were instructed to tweet the difficult concepts identified from content delivered by videos. A software program automatically collected and parsed the tweets to extract summary statistics on the most common difficult concepts, and the lecturer used the information to prepare face-to-face (F2F) lectorial sessions. The key findings of the study were 1) the uptake of Twitter (i.e., registration on the platform) was similar to the proportion of students who participated in F2F lectorials, 2) students reviewed content soon after delivery to tweet difficult concepts to lecturer, 3) Twitter increased engagement with lecturers, 4) the difficult concepts were similar to previous years, yet the automated gathering of Twitter data was more efficient and time saving for the lecturer, and 5) students found the lectorial review sessions very valuable.

The Enigma of the Adrenarche: Identifying the Early Life Mechanisms and Possible Role in Postnatal Brain Development.

Dehydroepiandrosterone (DHEA) and its sulfated metabolite (DHEAS) are dynamically regulated before birth and the onset of puberty. Yet, the origins and purpose of increasing DHEA[S] in postnatal development remain elusive. Here, we draw attention to this pre-pubertal surge from the adrenal gland-the adrenarche-and discuss whether this is the result of intra-adrenal gene expression specifically affecting the zona reticularis (ZR), if the ZR is influenced by the hypothalamic-pituitary axis, and the possible role of spino-sympathetic innervation in prompting increased ZR activity. We also discuss whether neural DHEA[S] synthesis is coordinately regulated with the developing adrenal gland. We propose that DHEA[S] is crucial in the brain maturation of humans prior to and during puberty, and suggest that the function of the adrenarche is to modulate, adapt and rewire the pre-adolescent brain for new and ever-changing social challenges. The etiology of DHEA[S] synthesis, neurodevelopment and recently described 11-keto and 11-oxygenated androgens are difficult to investigate in humans owing to: (i) ethical restrictions on mechanistic studies, (ii) the inability to predict which individuals will develop specific mental characteristics, and (iii) the difficulty of conducting retrospective studies based on perinatal complications. We discuss new opportunities for animal studies to overcome these important issues.

Central leptin and resistin combined elicit enhanced central effects on renal sympathetic nerve activity.

NEW FINDINGS: What is the central question of this study? Leptin and resistin act centrally to increase renal sympathetic nerve activity (RSNA). We investigated whether a combination of resistin and leptin could induce a greater response than either alone. We also used Fos protein to quantify the number of activated neurons in the brain. What is the main finding and its importance? A combination of leptin and resistin induced a greater increase in RSNA than either hormone alone. This was correlated with a greater number of activated neurons in the arcuate nucleus than with either hormone alone. Leptin and resistin act centrally to increase renal sympathetic nerve activity (RSNA). We investigated whether a combination of resistin and leptin could induce a greater response than either alone. Mean arterial pressure, heart rate and RSNA were recorded before and for 3 h after intracerebroventricular saline (control; n = 5), leptin (7 µg; n = 5), resistin (7 µg; n = 4) and leptin administered 15 min after resistin (n = 6). Leptin alone and resistin alone significantly increased RSNA (74 ± 17 and 50 ± 14%, respectively; P < 0.0001 compared with saline). When leptin and resistin were combined, there was a significantly greater increase in RSNA (163 ± 23%) compared with either hormone alone (P < 0.0001). Maximal responses of mean arterial pressure and heart rate were not significantly different between groups. We also used Fos protein to quantify the number of activated neurons in the brain. Compared with controls, there were significant increases in numbers of Fos-positive neurons in the arcuate and hypothalamic paraventricular nuclei when leptin or resistin was administered alone or when they were combined, and in the lamina terminalis when leptin and resistin were combined. Only in the arcuate nucleus was the increase significantly greater compared with either hormone alone. The findings show that a combination of leptin and resistin induces a greater RSNA increase and a greater number of activated neurons in the arcuate nucleus than with either hormone alone. Given that leptin makes an important contribution to the elevated RSNA observed in obese and overweight conditions, the increased concentrations of leptin and resistin may mean that the contribution of leptin to the elevated RSNA in those conditions is enhanced.

New Insights Into the Role of Inflammation in the Brain in Heart Failure.

Heart failure is a growing medical problem. Although the underlying aetiology of heart failure differs according to the phenotype, there are some common characteristics observed in patients with heart failure. These include an increased sympathetic nerve activity, an activated renin-angiotensin system, and inflammation. The mechanisms mediating the increased sympathetic activity are not completely understood but the central nervous system plays a major role. Activation of the renin-angiotensin system plays an active role in the remodelling of the heart and in fluid and electrolyte imbalance. The presence of a central renin-angiotensin system means that locally produced angiotensin in the brain may also play a key role in autonomic dysfunction seen in heart failure. Markers of inflammation in the heart and in the circulation are observed in patients diagnosed with heart failure. Circulating pro-inflammatory cytokines can also influence cardiac function further afield than just locally in the heart including actions within the brain to activate the sympathetic nervous system. Preclinical evidence suggests that targeting the pro-inflammatory cytokines would be a useful therapy to treat heart failure. Most clinical studies have been disappointing. This mini-review suggests that pro-inflammatory cytokines in the brain play a key role and there is a problem associated with access of effective doses of the drugs to the site of action in the brain. The recent advances in nanotechnology delivery techniques may provide exciting future technology to investigate the role of specific pro-inflammatory mediators as novel targets within the brain in the treatment of heart failure.

AT1 receptors in the paraventricular nucleus mediate the hyperthermia-induced reflex reduction of renal blood flow in rats.

Increasing body core temperature reflexly decreases renal blood flow (RBF), and the hypothalamic paraventricular nucleus (PVN) plays an essential role in this response. ANG II in the brain is involved in the cardiovascular responses to hyperthermia, and ANG II receptors are highly concentrated in the PVN. The present study investigated whether ANG II in the PVN contributes to the cardiovascular responses elicited by hyperthermia. Rats anesthetized with urethane (1-1.4 g/kg iv) were microinjected bilaterally into the PVN (100 nl/side) with saline (n = 5) or losartan (1 nmol/100 nl) (n = 7), an AT1 receptor antagonist. Body core temperature was then elevated from 37°C to 41°C and blood pressure (BP), heart rate (HR), RBF, and renal vascular conductance (RVC) were monitored. In separate groups losartan (n = 4) or saline (n = 4) was microinjected into the PVN, but body core temperature was not elevated. Increasing body core temperature in control rats elicited significant decreases in RBF (-48 ± 5% from a resting level of 14.3 ± 1.4 ml/min) and MVC (-40 ± 4% from a resting level of 0.128 ± 0.013 ml/min·mmHg), and these effects were entirely prevented by pretreatment with losartan. In rats in which body core temperature was not altered, losartan microinjected into the PVN had no significant effects on these variables. The results suggest that endogenous ANG II acts on AT1 receptors in the PVN to mediate the reduction in RBF induced by hyperthermia.

Cardiovascular and Metabolic Crosstalk in the Brain: Leptin and Resistin.

Leptin and resistin are cytokines whose plasma levels correlate with adiposity. Leptin is a hormone synthesised and released from adipocytes and can be transported into the brain. Resistin is produced in adipocytes in rodents and in macrophages in humans, particularly macrophages that have infiltrated adipose tissue. Both hormones can act within the brain to influence sympathetic nerve activity. Leptin appears to have a generalised sympatho-excitatory actions whilst resistin appears to increase sympathetic nerve activity affecting the cardiovascular system but inhibits sympathetic nerve activity to brown adipose tissue, which contrasts with leptin. Since both hormones can be elevated in conditions of metabolic dysfunction, interactions/crosstalk between these two hormones in the brain is a real possibility. This review describes the current knowledge regarding such crosstalk within the central nervous system. The evidence suggests that with respect to sympathetic nerve activity, crosstalk between leptin and resistin can elicit enhanced sympatho-excitatory responses to the kidneys. In contrast, with respect to food intake, resistin has weaker effects, but in regard to insulin secretion and thermogenesis, leptin and resistin have opposing actions. Thus, in conditions in which there is increased resistin and leptin levels, the result of crosstalk in the central nervous system could contribute to worse cardiovascular and metabolic complications.

Role of the hypothalamic PVN in the regulation of renal sympathetic nerve activity and blood flow during hyperthermia and in heart failure.

The hypothalamic paraventricular nucleus is a key integrative area in the brain involved in influencing sympathetic nerve activity and in the release of hormones or releasing factors that contribute to regulating body fluid homeostasis and endocrine function. The endocrine and hormonal regulatory function of the paraventricular nucleus is well studied, but the regulation of sympathetic nerve activity and blood flow by this region is less clear. Here we review the critical role of the paraventricular nucleus in regulating renal blood blow during hyperthermia and the evidence pointing to an important pathophysiological role of the paraventricular nucleus in the elevated renal sympathetic nerve activity that is a characteristic of heart failure.

High-fat feeding alters the cardiovascular role of the hypothalamic paraventricular nucleus.

Increased sympathetic nerve activity is associated with obesity-related hypertension, but the underlying central neural mechanisms are not clear. We examined the role of the hypothalamic paraventricular nucleus (PVN) in the regulation of sympathetic nerve activity in rats fed a normal chow diet (controls) and rats fed a high-fat diet (36% fat) over 12 wk. The effects on blood pressure, heart rate, and lumbar sympathetic nerve activity (LSNA) induced by microinjection of the GABA(A) receptor agonist muscimol or the antagonist bicuculline were monitored in anesthetized rats. Body weight of rats fed the high-fat diet was not significantly different from controls, but a significant 80% increase in epididymal fat mass, significantly elevated fasting blood glucose, and significantly impaired glucose tolerance were observed in rats fed the high-fat diet. Resting blood pressure and heart rate were not significantly different between rats fed the high-fat diet and controls. Muscimol microinjected into the PVN elicited a greater reduction of blood pressure and LSNA in rats fed the high-fat diet than controls: -14 +/- 6 vs. -7 +/- 2 mmHg and -35 +/- 6 vs. -10 +/- 9% (P < 0.05). Microinjection of bicuculline into the PVN increased blood pressure and LSNA, but the responses were similar in rats fed the high-fat diet and controls. In conclusion, the role of the paraventricular nucleus in cardiovascular regulation can be altered by a diet high in fat, even when hypertension and obesity are absent.

Inhibition of nitric oxide synthase in the paraventricular nucleus prevents the hyperthermia-induced reduction of mesenteric blood flow in rats.

Increasing body core temperature reflexly decreases mesenteric blood flow (MBF), and the hypothalamic paraventricular nucleus (PVN) plays an essential role in this response. Nitric oxide (NO) is involved in temperature regulation and is concentrated within the PVN. The present study investigated whether NO in the PVN contributes to the cardiovascular responses elicited by hyperthermia. Anesthetized rats were microinjected bilaterally in the PVN (100 nl/side) with saline or N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor (100 or 200 nmol/100 nl) (n = 5/group). Body core temperature was then elevated from 37 degrees C to 39 degrees C, and blood pressure (BP), heart rate (HR), MBF, and mesenteric vascular conductance (MVC) were monitored. In separate groups, L-NAME (200 nmol) (n = 5) or saline (n = 5) was microinjected in the PVN, but body core temperature was not elevated. In control rats, increasing body core temperature resulted in no marked change of BP but an increase in HR and significant decreases in MBF (15%) and MVC. Pretreatment with 100 nmol L-NAME did not affect the responses. In contrast, 200 nmol L-NAME prevented the normal reduction in MBF and MVC but did not significantly affect the BP and HR responses. In rats in which body core temperature was not increased, L-NAME reduced MBF by 19%. The present results suggest that endogenous NO in the PVN is important in mediating the reduction of MBF induced by hyperthermia. In the absence of hyperthermia, however, endogenous NO in the PVN may play a role in maintaining mesenteric vasodilation.

The Carotid Body a Common Denominator for Cardiovascular and Metabolic Dysfunction?

The carotid body is a highly vascularized organ designed to monitor oxygen levels. Reducing oxygen levels in blood results in increased activity of the carotid body cells and reflex increases in sympathetic nerve activity. A key contributor to elevated sympathetic nerve activity in neurogenic forms of hypertension is enhanced peripheral chemoreceptor activity. Hypertension commonly occurs in metabolic disorders, like obesity. Such metabolic diseases are serious global health problems. Yet, the mechanisms contributing to increased sympathetic nerve activity and hypertension in obesity are not fully understood and a better understanding is urgently required. In this review, we examine the literature that suggests that overactivity of the carotid body may also contribute to metabolic disturbances. The purine ATP is an important chemical mediator influencing the activity of the carotid body and the role of purines in the overactivity of the carotid body is explored. We will conclude with the suggestion that tonic overactivity of the carotid body may be a common denominator that contributes to the hypertension and metabolic dysfunction seen in conditions in which metabolic disease exists such as obesity or insulin resistance induced by high caloric intake. Therapeutic treatment targeting the carotid bodies may be a viable treatment since translation to the clinic could be more easily performed than expected via repurposing antagonists of purinergic receptors currently in clinical practice, and the use of other minimally invasive techniques that reduce the overactivity of the carotid bodies which may be developed for such clinical use.

Central Administration of Insulin Combined With Resistin Reduces Renal Sympathetic Nerve Activity in Rats Fed a High Fat Diet.

Insulin receptors are widely distributed in the central nervous system and their activation by insulin elicits renal sympatho-excitatory effects. Resistin, an adipokine, promotes resistance to the metabolic effects of insulin. Resistin also induces increases in renal sympathetic nerve activity (RSNA) by acting in the brain, but whether it can influence insulin's actions on RSNA is unknown. In the present study we investigated, in male Sprague-Dawley rats (7-8 weeks of age), the effects of central administration of insulin combined with resistin on RSNA following a normal diet (ND) and a high fat diet (HFD) (22% fat), since HFD can reportedly attenuate insulin's actions. RSNA, mean arterial pressure (MAP) and heart rate (HR) responses were monitored and recorded before and for 180 min after intracerebroventricular injection of saline (control) (n = 5 HFD and ND), resistin (7 µg; n = 4 ND, n = 5 HFD), insulin (500 mU; n = 6 ND, n = 5 HFD), and the combination of both resistin and insulin (n = 7 ND, n = 5 HFD). The key finding of the present study was that when resistin and insulin were combined there was no increase in RSNA induced in rats fed a normal diet or the high fat diet. This contrasted with the sympatho-excitatory RSNA effects of the hormones when each was administered alone in rats fed the ND and the HFD.

A tale of two steroids: The importance of the androgens DHEA and DHEAS for early neurodevelopment.

DHEA and DHEAS are neuroactive neurosteroids that interact with several major receptor systems in the brain, including sigma (σ), glutamate, and GABA-A receptors. It has been recognized as early as 1952, that the loss of DHEA/DHEAS in adult life is associated with neuropsychiatric disorders (eg schizophrenia, depression). However, the mechanistic role for DHEA/DHEAS in any of these domains remains speculative, not the least because the presence of these androgens in the adrenal gland and brain is largely confined to humans and only some non-human primates. DHEA and DHEAS are dynamically regulated from before birth and before the onset of puberty, and therefore an understanding of the synthesis, regulation, and functions of this important androgen pathway warrants attention. Here, we draw attention to the possible modulating influence of DHEA/DHEAS in early brain development from fetal life to the remarkable increase of these steroids in early childhood - the adrenarche. We propose that the pre-pubertal DHEA/DHEAS surge plays a key role in modulating early brain development, perhaps by prolonging brain plasticity during childhood to allow the pre-adolescent brain to adapt and re-wire in response to new, and ever-changing social challenges. Nonetheless, the aetiology of neurodevelopmental phenomena in relation to DHEA/DHEAS synthesis and action cannot be easily studied in humans due to the obvious ethical restrictions on mechanistic studies, the uncertainty of predicting the future mental characteristics of individuals, and the difficulty of conducting retrospective investigations based on pre-birth and/or neonatal complications. We discuss new opportunities for animal studies to resolve these important questions.

DHEA in Prenatal and Postnatal Life: Implications for Brain and Behavior.

Dehydroepiandrosterone (DHEA) and its sulfated congener (DHEAS) are the principal C19 steroid produced by the adrenal gland in many mammals, including humans. It is secreted in high concentrations during fetal life, but synthesis decreases after birth until, in humans and some other primates, there is a prepubertal surge of DHEA production by the adrenal gland-a phenomenon known as adrenarche. There remains considerable uncertainty about the physiological role of DHEA and DHEAS. Moreover, the origin of the trophic drives that determine the waxing and waning of DHEA synthesis are poorly understood. These gaps in knowledge arise in some measure from the difficulty of understanding mechanistic determinants from observations made opportunistically in humans and primates, and have stimulated a search for other suitable species that exhibit adrenarche- and adrenopause-like changes of adrenal function. DHEA and DHEAS are clearly neuroactive steroids with actions at several neurotransmitter receptors; indeed, DHEA is now known to be also synthesized by many parts of the brain, and this capacity undergoes ontogenic changes, but whether this is dependent or independent of the changes in adrenal synthesis is unknown. In this chapter we review key contributions to this field over the last 50+ years, and speculate on the importance of DHEA for the brain, both during development and for maturation and aging of cerebral function and behavior.

High Fat Diet Decreases Neuronal Activation in the Brain Induced by Resistin and Leptin.

Resistin and leptin are adipokines which act in the brain to regulate metabolic and cardiovascular functions which in some instances are similar, suggesting activation of some common brain pathways. High-fat feeding can reduce the number of activated neurons observed following the central administration of leptin in animals, but the effects on resistin are unknown. The present work compared the distribution of neurons in the brain that are activated by centrally administered resistin, or leptin alone, and, in combination, in rats fed a high fat (HFD) compared to a normal chow diet (ND). Immunohistochemistry for the protein, Fos, was used as a marker of activated neurons. The key findings are (i) following resistin or leptin, either alone or combined, in rats fed the HFD, there were no significant increases in the number of activated neurons in the paraventricular and arcuate nuclei, and in the lateral hypothalamic area (LHA). This contrasted with observations in rats fed a normal chow diet; (ii) in the OVLT and MnPO of HFD rats there were significantly less activated neurons compared to ND following the combined administration of resistin and leptin; (iii) In the PAG, RVMM, and NTS of HFD rats there were significantly less activated neurons compared to ND following resistin. The results suggest that the sensitivity to resistin in the brain was reduced in rats fed a HFD. This has similarities with leptin but there were instances where there was reduced sensitivity to resistin with no significant effects following leptin. This suggests diet influences neuronal effects of resistin.

In situ hybridization using riboprobes on free-floating brain sections.

A method is described for in situ hybridization of riboprobes to free-floating brain sections. Brain sections are hybridized and processed free-floating in buffer, i.e., without attachment to a support such as a slide. To withstand the extra wear compared with sections processed on-slide, the brain tissue must be well fixed (4% paraformaldehyde) and sections cut at thickness of typically 40 microm. Sections were exposed to a prehybridization treatment before a riboprobe is added to form the hybridization solution. Riboprobes were prepared from cDNA via an in vitro transcription reaction and are labeled with digoxigenin. The sections are subsequently processed to remove nonspecific binding and the digoxigenin label detected via an antibody conjugated to alkaline phosphatase. This method may be readily combined with neuronal tracing and is ideal for further processing by immunohistochemistry to detect specific proteins.

Central Administration of Insulin and Leptin Together Enhance Renal Sympathetic Nerve Activity and Fos Production in the Arcuate Nucleus.

There is considerable interest in the central actions of insulin and leptin. Both induce sympatho-excitation. This study (i) investigated whether centrally administered leptin and insulin together elicits greater increases in renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) than when given alone, and (ii) quantified the number of activated neurons in brain regions influencing SNA, to identify potential central sites of interaction. In anesthetised (urethane 1.4-1.6 g/kg iv) male Sprague-Dawley rats, RSNA, MAP, and HR were recorded following intracerebroventricular (ICV) saline (control; n = 5), leptin (7 µg; n = 5), insulin (500 mU; n = 4) and the combination of leptin and insulin; (n = 4). Following leptin or insulin alone, RSNA was significantly increased (74 and 62% respectively). MAP responses were not significantly different between the groups. Insulin alone significantly increased HR. Leptin alone also increased HR but it was significantly less than following insulin alone (P < 0.005). When leptin and insulin were combined, the RSNA increase (124%) was significantly greater than the response to either alone. There were no differences between the groups in MAP responses, however, the increase in HR induced by insulin was attenuated by leptin. Of the brain regions examined, only in the arcuate nucleus did leptin and insulin together increase the number of Fos-positive cell nuclei significantly more than leptin or insulin alone. In the lamina terminalis and rostroventrolateral medulla, leptin and insulin together increased Fos, but the effect was not greater than leptin alone. The results suggest that when central leptin and insulin levels are elevated, the sympatho-excitatory response in RSNA will be greater. The arcuate nucleus may be a common site of cardiovascular integration.

nNOS-containing neurons in the hypothalamus and medulla project to the RVLM.

Nitric oxide (NO) within the brain is known to have an important influence on sympathetic nerve activity (SNA). NO is found in the paraventricular nucleus (PVN), caudal ventrolateral medulla (CVLM) and the nucleus tractus solitarius (NTS), regions that project to the rostral ventrolateral medulla (RVLM), an area that is critical in the regulation of SNA. The aim of the present study was to determine whether neurons in the PVN, NTS and CVLM that project to the RVLM contain the neuronal isoform of nitric oxide synthase (nNOS) and are, therefore, capable of producing NO. Under pentobarbitone general anaesthesia, the retrogradely-transported tracer, rhodamine-tagged microspheres, were microinjected into the RVLM of rats (n = 6). Two weeks later, the animals were re-anaesthetised, perfused with para-formaldehyde and the brains were removed. Hypothalamic and medullary sections were processed for nNOS immunohistochemistry and the RVLM-projecting neurons were identified using fluorescence microscopy. We found nNOS-containing neurons were present throughout the PVN, CVLM and NTS and that these were intermingled with neurons that projected to the RVLM. Of the neurons in the PVN and CVLM that projected to the RVLM, approximately 12 +/- 1% and 8 +/- 3%, respectively, contained nNOS. In the NTS only 1 +/- 1% of the neurons were double-labeled. This study highlights anatomical pathways emanating from the PVN and CVLM, in particular, which may contribute to the effects on SNA elicited by NO within the brain.

Resistin, an Adipokine with Non-Generalized Actions on Sympathetic Nerve Activity.

The World Health Organization has called obesity a global epidemic. There is a strong association between body weight gain and blood pressure. A major determinant of blood pressure is the level of activity in sympathetic nerves innervating cardiovascular organs. A characteristic of obesity, in both humans and in animal models, is an increase in sympathetic nerve activity to the skeletal muscle vasculature and to the kidneys. Obesity is now recognized as a chronic, low level inflammatory condition, and pro-inflammatory cytokines are elevated including those produced by adipose tissue. The most well-known adipokine released from fat tissue is leptin. The adipokine, resistin, is also released from adipose tissue. Resistin can act in the central nervous system to influence the sympathetic nerve activity. Here, we review the effects of resistin on sympathetic nerve activity and compare them with leptin. We build an argument that resistin and leptin may have complex interactions. Firstly, they may augment each other as both are excitatory on sympathetic nerves innervating cardiovascular organs; In contrast, they could antagonize each other's actions on brown adipose tissue, a key metabolic organ. These interactions may be important in conditions in which leptin and resistin are elevated, such as in obesity.

Tonic sympathoinhibition arising from the hypothalamic PVN in the conscious rabbit.

In the conscious rabbit muscimol (1-10 nmol/side) was microinjected into the hypothalamic paraventricular nucleus to inhibit neuronal function and the acute changes in mean arterial pressure (MAP), heart rate and renal sympathetic nerve activity (RSNA) were monitored. Muscimol (1 nmol) had no effect on the cardiovascular variables, as was the case with vehicle. However, muscimol (10 nmol) elicited a significant increase in RSNA of 184+/-40% and a reduction in heart rate of 49+/-12 beats/min but no change in MAP. The effect of blocking endogenous glutamatergic inputs with the glutamate antagonist, kynurenate (25 nmol), into the PVN was also examined. Kynurenate elicited an increase in RSNA of 35+/-9% with no significant change in MAP or HR. The results suggest that muscimol inhibits a tonically active inhibitory influence on RSNA arising from the PVN in the conscious rabbit. A glutamatergic input into the PVN appears to contribute to the tonic activation of this inhibitory influence.