Descending pathways from the superior colliculus mediating autonomic and respiratory effects associated with orienting behaviour.

The ability to discriminate competing external stimuli and initiate contextually appropriate behaviours is a key brain function. Neurons in the deep superior colliculus (dSC) integrate multisensory inputs and activate descending projections to premotor pathways responsible for orienting, attention and defence, behaviours which involve adjustments to respiratory and cardiovascular parameters. However, the neural pathways that subserve the physiological components of orienting are poorly understood.

Resetting of the Baroreflex Control of Sympathetic Vasomotor Activity during Natural Behaviors: Description and Conceptual Model of Central Mechanisms.

The baroreceptor reflex controls arterial pressure primarily via reflex changes in vascular resistance, rather than cardiac output. The vascular resistance in turn is dependent upon the activity of sympathetic vasomotor nerves innervating arterioles in different vascular beds. In this review, the major theme is that the baroreflex control of sympathetic vasomotor activity is not constant, but varies according to the behavioral state of the animal.

Central neural control of the cardiovascular system: current perspectives.

This brief review, which is based on a lecture presented at the American Physiological Society Teaching Refresher Course on the Brain and Systems Control as part of the Experimental Biology meeting in 2015, aims to summarize current concepts of the principal mechanisms in the brain that regulate the autonomic outflow to the cardiovascular system. Such cardiovascular regulatory mechanisms do not operate in isolation but are closely coordinated with respiratory and other regulatory mechanisms to maintain homeostasis. The brain regulates the cardiovascular system by two general means: 1) feedforward regulation, often referred to as "central command," and 2) feedback or reflex regulation.

Brain-heart interactions: physiology and clinical implications.

The brain controls the heart directly through the sympathetic and parasympathetic branches of the autonomic nervous system, which consists of multi-synaptic pathways from myocardial cells back to peripheral ganglionic neurons and further to central preganglionic and premotor neurons. Cardiac function can be profoundly altered by the reflex activation of cardiac autonomic nerves in response to inputs from baro-, chemo-, nasopharyngeal and other receptors as well as by central autonomic commands, including those associated with stress, physical activity, arousal and sleep. In the clinical setting, slowly progressive autonomic failure frequently results from neurodegenerative disorders, whereas autonomic hyperactivity may result from vascular, inflammatory or traumatic lesions of the autonomic nervous system, adverse effects of drugs and chronic neurological disorders.

Coordinated autonomic and respiratory responses evoked by alerting stimuli: Role of the midbrain colliculi.

Threatening stimuli trigger rapid and coordinated behavioral responses supported by cardiorespiratory changes. The midbrain colliculi can generate coordinated orienting or defensive behavioral responses, and it has been proposed that collicular neurons also generate appropriate cardiovascular and respiratory responses to support such behaviors. We have shown previously that under conditions where collicular neurons are disinhibited, coordinated cardiovascular, somatomotor and respiratory responses can be evoked independently of the cortex by auditory, visual and somatosensory stimuli.

Both Ox1R and Ox2R orexin receptors contribute to the cardiorespiratory response evoked from the perifornical hypothalamus.

Orexin/hypocretin neurons are located in and around the perifornical hypothalamus. Disinhibition of this area in the anaesthetized preparation evokes cardiorespiratory changes that can be reduced to nearly half or more by systemic Almorexant, a dual receptor antagonist of the two known orexin receptors, Ox1R and Ox2R. It is not clear if these reductions result from the blockade of one receptor or both.

Central mechanisms regulating coordinated cardiovascular and respiratory function during stress and arousal.

Actual or potentially threatening stimuli in the external environment (i.e., psychological stressors) trigger highly coordinated defensive behavioral responses that are accompanied by appropriate autonomic and respiratory changes.

Bidirectional interactions between the baroreceptor reflex and arousal: an update.

Studies involving genetic engineering on animal models and mathematical analysis of cardiovascular signals on humans are shedding new light on the interactions between the arterial baroreceptor reflex (baroreflex) and arousal. Baroreceptor stimulation, if very mild or performed under anaesthesia, may inhibit cortical arousal. However, substantial increases or decreases in baroreflex activation cause arousal in animal models and human subjects in physiological conditions.

Disinhibition of the midbrain colliculi unmasks coordinated autonomic, respiratory, and somatomotor responses to auditory and visual stimuli.

The midbrain superior and inferior colliculi have critical roles in generating coordinated orienting or defensive behavioral responses to environmental stimuli, and it has been proposed that neurons within the colliculi can also generate appropriate cardiovascular and respiratory responses to support such behavioral responses. We have previously shown that activation of neurons within a circumscribed region in the deep layers of the superior colliculus and in the central and external nuclei of the inferior colliculus can evoke a response characterized by intense and highly synchronized bursts of renal sympathetic nerve activity and phrenic nerve activity. In this study, we tested the hypothesis that, under conditions in which collicular neurons are disinhibited, coordinated cardiovascular, somatomotor, and respiratory responses can be evoked by natural environmental stimuli.

The effect of air puff stress on c-Fos expression in rat hypothalamus and brainstem: central circuitry mediating sympathoexcitation and baroreflex resetting.

Psychological stress evokes increases in sympathetic activity and blood pressure, which are due at least in part to an upward resetting of the baroreceptor-sympathetic reflex. In this study we determined whether sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM), which have a critical role in the reflex control of sympathetic activity, are activated during air puff stress, a moderate psychological stressor. Secondly, we identified neurons that are activated by air puff stress and that also project to the nucleus tractus solitarius (NTS), a key site for modulation of the baroreceptor reflex.

Central control of cardiovascular function during sleep.

There is increasing evidence that cardiovascular control during sleep is relevant for cardiovascular risk. This evidence warrants increased experimental efforts to understand the physiological mechanisms of such control. This review summarizes current knowledge on autonomic features of sleep states [non-rapid-eye-movement sleep (NREMS) and rapid-eye-movement sleep (REMS)] and proposes some testable hypotheses concerning the underlying neural circuits.

Role of dorsolateral periaqueductal grey in the coordinated regulation of cardiovascular and respiratory function.

The midbrain periaqueductal grey (PAG) contains four longitudinal columns, referred to as the dorsomedial (dmPAG), dorsolateral (dlPAG), lateral (lPAG) and ventrolateral (vlPAG) subdivisions, which collectively have a pivotal role in integrating behavioural and physiological responses to external stressors as well as other functions. This review is focussed on the dlPAG, which is believed to be an important component of the central mechanisms that generate the defensive response to acute psychological stressors, such as the presence of a predator or other immediate threat. The anatomical connections of the dlPAG are highly specific and distinctly different from those of the other PAG subregions.

Blockade of orexin receptors with Almorexant reduces cardiorespiratory responses evoked from the hypothalamus but not baro- or chemoreceptor reflex responses.

Orexin neurons form a restricted group in the dorsal hypothalamus. The group is centered on the perifornical area within the classic hypothalamic defense area, an area which when activated produces marked cardiovascular and respiratory effects. Central administration of orexin can produce cardiorespiratory effects, but the extent to which orexin contributes to such responses evoked from the perifornical hypothalamus is not clear.

Synchronized activation of sympathetic vasomotor, cardiac, and respiratory outputs by neurons in the midbrain colliculi.

The superior and inferior colliculi are believed to generate immediate and highly coordinated defensive behavioral responses to threatening visual and auditory stimuli. Activation of neurons in the superior and inferior colliculi have been shown to evoke increases in cardiovascular and respiratory activity, which may be components of more generalized stereotyped behavioral responses. In this study, we examined the possibility that there are "command neurons" within the colliculi that can simultaneously drive sympathetic and respiratory outputs.

Activation of 5-hydroxytryptamine-1A receptors suppresses cardiovascular responses evoked from the paraventricular nucleus.

Activation of central 5-hydroxytryptamine-1A (5-HT(1A)) receptors powerfully inhibits stress-evoked cardiovascular responses mediated by the dorsomedial hypothalamus (DMH), as well as responses evoked by direct activation of neurons within the DMH. The hypothalamic paraventricular nucleus (PVN) also has a crucial role in cardiovascular regulation and is believed to regulate heart rate and renal sympathetic activity via pathways that are independent of the DMH. In this study, we determined whether cardiovascular responses evoked from the PVN are also modulated by activation of central 5-HT(1A) receptors.

Topographical specificity of regulation of respiratory and renal sympathetic activity by the midbrain dorsolateral periaqueductal gray.

The midbrain periaqueductal gray (PAG) mediates the physiological responses to a wide range of stressors. It consists of four longitudinal columns that have different anatomical connections and functional properties. Previous anatomical and behavioral studies have led to the hypothesis that the dorsolateral PAG, but not the adjacent lateral and dorsomedial subregions, is a key center that integrates the behavioral response to acute psychological threatening stimuli.

Pregnancy and the endocrine regulation of the baroreceptor reflex.

The purpose of this review is to delineate the general features of endocrine regulation of the baroreceptor reflex, as well as specific contributions during pregnancy. In contrast to the programmed changes in baroreflex function that occur in situations initiated by central command (e.g.

Vasomotor and respiratory responses evoked from the dorsolateral periaqueductal grey are mediated by the dorsomedial hypothalamus.

Activation of neurons in the dorsomedial hypothalamus (DMH) evokes increases in mean arterial pressure (MAP), sympathetic activity, heart rate (HR) and respiratory activity. Results of previous studies suggest that the DMH-evoked increases in MAP and HR are mediated by neurons within the periaqueductal grey (PAG), but a recent study has proposed that the converse is also true, i.e.

Role of 5-HT(1A) receptors in the lower brainstem on the cardiovascular response to dorsomedial hypothalamus activation.

The dorsomedial hypothalamus (DMH) is an essential brain region for the integration of the physiological response to psychological stressors. The cardiovascular components of the response include increases in blood pressure, heart rate and the activity of sympathetic nerves to the kidney, skin, brown adipose tissue, and heart. Neurons in the rostral ventrolateral medulla (RVLM) and in the region of the medullary raphe are important components of the descending pathways that mediate the cardiovascular response to the DMH activation.