Search

In the cat four different types of vocalization, mews, howls, cries, and hisses were generated by microstimulation in different parts of the periaqueductal gray (PAG). While mews imply positive vocal expressions, howls, hisses, and cries represent negative vocal expressions. In the intermediate PAG, mews were generated in the lateral column, howls, and hisses in the ventrolateral column. Cries were generated in two other regions, the lateral column of the rostral PAG and the ventrolateral column of the caudal PAG. In order to define the specific motor patterns of the mews, howls, and cries, the following muscles were recorded during these vocalizations; larynx (cricothyroid, thyroarytenoid, and posterior cricoarytenoid), tongue (genioglossus), jaw (digastric), and respiration muscles (diaphragm, internal intercostal, external, and internal abdominal oblique). During these mews, howls, and cries we analyzed the frequency, intensity, activation cascades power density, turns, and amplitude analysis of the electromyograms (EMGs). It appeared that each type of vocalization consists of a specific circumscribed motor coordination. The nucleus retroambiguus (NRA) in the caudal medulla is known to serve as the final premotor interneuronal output system for vocalization. Although neurochemical microstimulation in the NRA itself also generated vocalizations, they only consisted of guttural sounds, the EMGs of which involved only small parts of the EMGs of the mews, howls, and cries generated by neurochemical stimulation in the PAG. These results demonstrate that positive and negative vocalizations are generated in different parts of the PAG. These parts have access to different groups of premotoneurons in the NRA, that, in turn, have access to different groups of motoneurons in the brainstem and spinal cord, resulting in different vocalizations. The findings would serve a valuable model for diagnostic assessment of voice disorders in humans.

The nucleus retroambiguus (NRA) is a neuronal cell group in the medullary ventrolateral tegmentum, rostrocaudally between the obex and the first cervical spinal segment. NRA neurons are premotor interneurons with direct projections to the motoneurons of soft palate, pharynx, and larynx in the nucleus ambiguus in the lateral medulla as well as to the motoneurons in the spinal cord innervating diaphragm, abdominal, and pelvic floor muscles and the lumbosacral motoneurons generating sexual posture. These NRA premotor interneurons receive very strong projections from the periaqueductal gray (PAG) in the context of basic survival mechanisms as fight, flight, freezing, sound production, and sexual behavior. In the present study in rat we investigated the physiological motor patterns generated by NRA neurons, as the result of vagal, peripheral chemosensory, and nociceptive stimulation. The results show that the NRA contains phasic respiratory modulated neurons, as well as nonphasic tonically modulated neurons. Stimulation in the various rostrocaudal levels of the NRA generates site-specific laryngeal, respiratory, abdominal, and pelvic floor motor activities. Vagal and peripheral chemosensory stimulation induces both excitatory and inhibitory modulation of phasic NRA-neurons, while peripheral chemosensory and nociceptive stimulation causes excitation and inhibition of nonphasic NRA-neurons. These results are in agreement with the concept that the NRA represents a multifunctional group of neurons involved in the output of the emotional motor system, such as vomiting, vocalization, mating, and changes in respiration.

Vocalizations such as mews and cries in cats or crying and laughter in humans are examples of expression of emotions. These vocalizations are generated by the emotional motor system, in which the mesencephalic periaqueductal gray (PAG) plays a central role, as demonstrated by the fact that lesions in the PAG lead to complete mutism in cats, monkeys, as well as in humans. The PAG receives strong projections from higher limbic regions and from the anterior cingulate, insula, and orbitofrontal cortical areas. In turn, the PAG has strong access to the caudal medullary nucleus retroambiguus (NRA). The NRA is the only cell group that has direct access to the motoneurons involved in vocalization, i.e., the motoneuronal cell groups innervating soft palate, pharynx, and larynx as well as diaphragm, intercostal, abdominal, and pelvic floor muscles. Together they determine the intraabdominal, intrathoracic, and subglottic pressure, control of which is necessary for generating vocalization. Only humans can speak, because, via the lateral component of the volitional or somatic motor system, they are able to modulate vocalization into words and sentences. For this modulation they use their motor cortex, which, via its corticobulbar fibers, has direct access to the motoneurons innervating the muscles of face, mouth, tongue, larynx, and pharynx. In conclusion, humans generate speech by activating two motor systems. They generate vocalization by activating the prefrontal-PAG-NRA-motoneuronal pathway, and, at the same time, they modulate this vocalization into words and sentences by activating the corticobulbar fibers to the face, mouth, tongue, larynx, and pharynx motoneurons.

Neurochemical microstimulation in different parts of the midbrain periaqueductal gray (PAG) in the cat generates four different types of vocalization, mews, howls, cries, and hisses. Mews signify positive vocal expression, whereas howls, hisses, and cries signify negative vocal communications. Mews were generated in the lateral column of the intermediate PAG and howls and hisses in the ventrolateral column of the intermediate PAG. Cries were generated in two regions, the lateral column of the rostral PAG and the ventrolateral column of the caudal PAG. To define the specific motor patterns belonging to mews, howls, and cries, the following muscles were recorded during these vocalizations: larynx (cricothyroid, thyroarytenoid, and posterior cricoarytenoid), tongue (genioglossus), jaw (digastric), and respiration (diaphragm, internal intercostal, external abdominal oblique, and internal abdominal oblique) muscles. Furthermore, the frequency, intensity, activation cascades, and turns and amplitude analyses of the electromyograms (EMGs) during these vocalizations were analyzed. The results show that each type of vocalization consists of a specific, circumscribed motor coordination. The nucleus retroambiguus (NRA) in the caudal medulla serves as the final premotor interneuronal output system for vocalization. NRA neurochemical microstimulation also generated vocalizations (guttural sounds). Analysis of the EMGs demonstrated that these vocalizations consist of only small parts of the emotional voalizations generated by neurochemical stimulation in the PAG. These results demonstrate that motor organization of positive and negative emotional vocal expressions are segregated in the PAG and that the PAG uses the NRA as a tool to gain access to the motoneurons generating vocalization.

Achtergrond: Het is algemeen bekend dat Brodmanns area 17 (BA 17), de primaire visuele cortex, een fundamentele rol speelt in basale overlevingsmechanismen, aangezien visuele informatie van essentieel belang is bij het effectief reageren op gebeurtenissen in de directe omgeving van een individu. In de neuroimaging-studies waarin aan de vrijwilligers gevraagd wordt naar films te kijken, wordt de primaire visuele cortex op gelijke wijze gestimuleerd, ongeacht de inhoud van de visuele informatie. Alleen in sommige studies waarin de vrijwilligers gevraagd wordt zware niet-visuele taken te verrichten, is aangetoond dat de primaire visuele cortex gedeactiveerd wordt, ondanks dat de aangeboden hoeveelheid visuele informatie hetzelfde is. De vraag is dat of dat ook zo is wanneer de vrijwilligers naar zwak of sterk erotische films kijken, in vergelijking met neutrale films.

The midbrain periaqueductal gray (PAG) is involved in many basic survival behaviors that affect respiration. We hypothesized that the PAG promotes these behaviors by changing the firing of preinspiratory (pre-I) neurons in the pre-Botzinger complex, a cell group thought to be important in generating respiratory rhythm. We tested this hypothesis by recording single unit activity of pre-Botzinger pre-I neurons during stimulation in different parts of the PAG. Stimulation in the dorsal PAG increased the firing of pre-I neurons, resulting in tachypnea. Stimulation in the medial part of the lateral PAG converted the pre-I neurons into inspiratory phase-spanning cells, resulting in inspiratory apneusis. Stimulation in the lateral part of the lateral PAG generated an early onset of the pre-I neuronal discharge, which continued throughout the inspiratory phase, while at the same time attenuating diaphragm contraction. Stimulation in the ventral part of the lateral PAG induced tachypnea but inhibited pre-I cell firing, whereas stimulation in the ventrolateral PAG inhibited not only pre-I cells but also the diaphragm, leading to apnea. These findings show that PAG stimulation changes the activity of the pre-Botzinger pre-I neurons. These changes are in line with the different behaviors generated by the PAG, such as the dorsal PAG generating avoidance behavior, the lateral PAG generating fight and flight, and the ventrolateral PAG generating freezing and immobility. J. Comp. Neurol. 521: 3083-3098, 2013. (c) 2013 Wiley Periodicals, Inc.

Introduction The brain has two goals: survival of the individual and survival of the species. It ensures that the body resides in safe circumstances and can obtain sufficient drink and food. It also has to produce and protect offspring. Its most important tool is its motor system, which consists of the voluntary and emotional motor systems. Aim To explain how the brain uses its emotional motor system to control the pelvic organs. Methods Anatomic and physiologic data in cats and humans are used to find out how this motor system works and what parts of the brain and brainstem are involved. Main Outcome Measures Main outcome is that the brain control of the pelvic organs is a specific descending system. Results The pelvic organs are innervated by the sacral parasympathetic motoneurons, which are controlled by a specific group of neurons in the pontine brainstem, the pelvic organ stimulating center (POSC). Through long descending pathways, this POSC generates micturition, defecation, and sexual activities by stimulating different groups of sacral parasympathetic motoneurons. In turn the POSC is driven by the periaqueductal gray (PAG), which receives, through the sacral cord, precise information regarding the situation in all pelvic organs. In addition, the PAG receives instructions from higher brain levels such as the amygdala, bed nucleus of the stria terminalis, and various regions of the hypothalamus. Notably, in humans, the most important brain region having access to the PAG is the medial orbitofrontal cortex, which is deactivated in women with hypoactive sexual desire disorder. Conclusion In women with hypoactive sexual desire disorder, deactivation of their medial orbitofrontal cortex produces a decrease in PAG-POSC activation, causing absence of vaginal vasocongestion and lubrication and decreased sexual behavior in general. It often leads to major problems in their personal circumstances. The question is whether new drugs can cure this.

Micturition is, similar to all other movements of the body, the result of activation of the motor system in the central nervous system. This review explains how the brain and brainstem control micturition. The basic reflex system begins with a distinct cell group called Gert's Nucleus (GN) in the sacral cord. GN receives information about bladder contents via A-delta fibers from the bladder and bladder sphincter and relays this information to the central part of the midbrain periaqueductal gray (PAG), but not to the thalamus. The PAG, in turn, in case of substantial bladder filling, excites the pontine micturition center (PMC), which cell group, via its long descending pathways to the sacral cord, induces micturition. Higher brain regions in prefrontal cortex and limbic system, by means of its projections to the PAG are able to interrupt this basic reflex system. It allows the individual to postpone micturition until time and place are appropriate. Lesions in the pathways from prefrontal cortex and limbic system to the PAG probably cause urgeincontinence in the elderly. Neurourol. Urodynam. 29:42-48, 2010. (C) 2009 Wiley-Liss, Inc.

The role of the nucleus retroambiguus (NRA) in the context of respiration control has been subject of debate for considerable time. To solve this problem, we chemically (usingd,l-homocysteic acid) stimulated the NRA in unanesthetized precollicularly decerebrated cats and studied the respiratory effect via simultaneous measurement of tracheal pressure and electromyograms of diaphragm, internal intercostal (IIC), cricothyroid (CT), and external oblique abdominal (EO) muscles. NRA-stimulation 0–1 mm caudal to the obex resulted in recruitment of IIC muscle and reduction in respiratory frequency. NRA-stimulation 1–3 mm caudal to the obex produced vocalization along with CT activation and slight increase in tracheal pressure, but no change in respiratory frequency. NRA-stimulation 3–5 mm caudal to the obex produced CT muscle activation and an increase in respiratory frequency, but no vocalization. NRA-stimulation 5–8 mm caudal to the obex produced EO muscle activation and reduction in respiratory frequency. A change to the inspiratory effort was never observed, regardless of which NRA part was stimulated. The results demonstrate that NRA does not control eupneic inspiration but consists of topographically separate groups of premotor interneurons each producing detailed motor actions. These motor activities have in common that they require changes to eupneic breathing. Different combination of activation of these premotor neurons determines the final outcome, e.g., vocalization, vomiting, coughing, sneezing, mating posture, or child delivery. Higher brainstem regions such as the midbrain periaqueductal gray (PAG) decides which combination of NRA neurons are excited. In simple terms, the NRA is the piano, the PAG one of the piano players.

Neurochemical microstimulation in different parts of the midbrain periaqueductal gray (PAG) in the cat generates four different types of vocalization, mews, howls, cries, and hisses. Mews signify positive vocal expression, whereas howls, hisses, and cries signify negative vocal communications. Mews were generated in the lateral column of the intermediate PAG and howls and hisses in the ventrolateral column of the intermediate PAG. Cries were generated in two regions, the lateral column of the rostral PAG and the ventrolateral column of the caudal PAG. To define the specific motor patterns belonging to mews, howls, and cries, the following muscles were recorded during these vocalizations: larynx (cricothyroid, thyroarytenoid, and posterior cricoarytenoid), tongue (genioglossus), jaw (digastric), and respiration (diaphragm, internal intercostal, external abdominal oblique, and internal abdominal oblique) muscles. Furthermore, the frequency, intensity, activation cascades, and turns and amplitude analyses of the electromyograms (EMGs) during these vocalizations were analyzed. The results show that each type of vocalization consists of a specific, circumscribed motor coordination. The nucleus retroambiguus (NRA) in the caudal medulla serves as the final premotor interneuronal output system for vocalization. NRA neurochemical microstimulation also generated vocalizations (guttural sounds). Analysis of the EMGs demonstrated that these vocalizations consist of only small parts of the emotional voalizations generated by neurochemical stimulation in the PAG. These results demonstrate that motor organization of positive and negative emotional vocal expressions are segregated in the PAG and that the PAG uses the NRA as a tool to gain access to the motoneurons generating vocalization.

Vocalizations such as mews and cries in cats or crying and laughter in humans are examples of expression of emotions. These vocalizations are generated by the emotional motor system, in which the mesencephalic periaqueductal gray (PAG) plays a central role, as demonstrated by the fact that lesions in the PAG lead to complete mutism in cats, monkeys, as well as in humans. The PAG receives strong projections from higher limbic regions and from the anterior cingulate, insula, and orbitofrontal cortical areas. In turn, the PAG has strong access to the caudal medullary nucleus retroambiguus (NRA). The NRA is the only cell group that has direct access to the motoneurons involved in vocalization, i.e., the motoneuronal cell groups innervating soft palate, pharynx, and larynx as well as diaphragm, intercostal, abdominal, and pelvic floor muscles. Together they determine the intraabdominal, intrathoracic, and subglottic pressure, control of which is necessary for generating vocalization. Only humans can speak, because, via the lateral component of the volitional or somatic motor system, they are able to modulate vocalization into words and sentences. For this modulation they use their motor cortex, which, via its corticobulbar fibers, has direct access to the motoneurons innervating the muscles of face, mouth, tongue, larynx, and pharynx. In conclusion, humans generate speech by activating two motor systems. They generate vocalization by activating the prefrontal-PAG-NRA-motoneuronal pathway, and, at the same time, they modulate this vocalization into words and sentences by activating the corticobulbar fibers to the face, mouth, tongue, larynx, and pharynx motoneurons.

The lower urinary tract is responsible for the storage and periodic elimination of liquid waste from the body in the form of urine. The lower urinary tract consists of the urinary bladder and its outlet, the urethra, and is controlled by a complex set of pre- and postsynaptic autonomic and somatic motoneurons, which are in turn controlled by neurons in the spinal cord, pons, and midbrain. Conscious control of the lower urinary tract is maintained by the midbrain periaqueductal gray, which receives specific sensory input from the lower urinary tract and from higher brain regions, including the medial orbitofrontal cortex, which determines whether it is appropriate to void. This chapter outlines the organization of the neural pathways that innervate the lower urinary tract, how these pathways interact to control micturition and how the higher brain centers, in turn, control these pathways to maintain continence or allow micturition to take place.

By far, the strongest spinal cord projections to periaqueductal gray (PAG) and thalamus originate from the upper three cervical segments, but their precise organization and function are not known. In the present study in cat, tracer injections in PAG or in thalamus resulted in more than 2400 labeled cells, mainly contralaterally, in the first three cervical segments (C1-C3), in a 1:4 series of sections, excluding cells in the dorsal column and lateral cervical nuclei. These cells represent about 30% of all neurons in the entire spinal cord projecting to PAG and about 45% of all spinothalamic neurons. About half of the C1-C3 PAG and C1-C3 thalamic neurons were clustered laterally in the ventral horn (C1-3v1), bilaterally, with a slight ipsilateral preponderance. The highest numbers Of C1-3v1-PAG and C1-3v1-thalamic cells were found in C1, with the greatest density rostrocaudal ly in the middle part of C 1. A concept is put forward that C1-3v1 cells relay information from all levels of the cord to PAG and/or thalamus, although the processing of specific information from upper neck muscles and tendons or facet joints might also play a role. (c) 2005 Elsevier B.V. All rights reserved.

There is a close connection between micturition and emotion. Several species use micturition to signal important messages as territorial demarcation and sexual attraction. For this reason, micturition is coordinated not in the spinal cord but in the brainstem, where it is closely connected with the limbic system. In cat, bladder afferents terminate in a cell group in the lateral dorsal horn and lateral part of the intermediate zone. Neurons in this cell group project to supraspinal levels, not to the thalamus but to the central periaqueductal gray (PAG). Neurons in the lateral PAG, not receiving direct sacral cord afferents, project to the pontine micturition center (PMC). The PMC projects directly to the parasympathetic bladder motoneurons and to sacral GABA-ergic and glycinergic premotor interneurons that inhibit motoneurons in Onuf s nucleus innervating the external striated bladder sphincter. Thus, PMC stimulation causes bladder contraction and bladder sphincter relaxation, i.e., complete micturition. Other than the PAG, only the preoptic area and a cell group in the caudal hypothalamus project directly to the PMC. The ventromedial upper medullary tegmentum also sends projections to the PMC, but they are diffuse and also involve structures that adjoin the PMC. Neuroimaging studies in humans suggest that the systems controlling micturition in cat and human are very similar. It seems that the many structures in the brain that are known to influence micturition use the PAG as relay to the PMC. This basic organization has to be kept in mind in the fight against overactive bladder (OAB) and urge-incontinence.

The nucleus retroambiguus (NRA) of the caudal medulla is a relay nucleus by which neurons of the mesencephalic periaqueductal gray (PAG) reach motoneurons of pharynx, larynx, soft palate, intercostal and abdominal muscles, and several muscles of the hindlimbs. These PAG-NRA-motoneuronal projections are thought to play a role in survival behaviors, such as vocalization and mating behavior. In the present combined antero- and retrograde tracing study in the cat, we sought to determine whether the NRA, apart from the neurons projecting to motoneurons, also contains cells projecting back to the PAG. After injections of WGA-HRP in the caudal and intermediate PAG, labeled neurons were observed in the NRA, with a slight contralateral. preponderance. In contrast, after injections in the rostral PAG or adjacent deep tectal layers, no or very few labeled neurons were present in the NRA. After injection of [(3)H]leucine in the NRA, anterograde labeling was present in the most caudal ventrolateral and dorsolateral PAG, and slightly more rostrally in the lateral PAG, mainly contralaterally. When the [(3)H]leucine injection site extended medially into the medullary lateral tegmental field, labeling was found in most parts of the PAG as well as in the adjoining deep tectal layers. No labeled fibers were found in the dorsolateral PAG, and only a few were found in the rostral PAG. Because the termination pattern of the NRA fibers in the PAG overlaps with that of the sacral cord projections to the PAG, it is suggested that the NRA-PAG projections play a role in the control of motor functions related to mating behavior. J. Comp. Neurol. 445:47-58, 2002. (C) 2002 Wiley-Liss, Inc.

Modulation of respiration is a prerequisite for survival of the individual and of the species. For example, respiration has to be adjusted in case of speech, strenuous exercise, laughing, crying, or sudden escape from danger. Respiratory centers in pons and medulla generate the basic respiratory rhythm or eupnea, but they cannot modulate breathing in the context of emotional challenges, for which they need input from higher brain centers. In simple terms, the prefrontal cortex integrates visual, auditory, olfactory, and somatosensory information and informs subcortical structures such as amygdala, hypothalamus, and finally the midbrain periaqueductal gray (PAG) about the results. The PAG, in turn, generates the final motor output for basic survival, such as setting the level of all cells in the brain and spinal cord. Best known in this framework is determining the level of pain perception. The PAG also controls heart rate, blood pressure, micturition, sexual behavior, vocalization, and many other basic motor output systems. Within this context, the PAG also changes the eupneic respiratory rhythm into a breathing pattern necessary for basic survival. This review examines the latest developments regarding of how the PAG controls respiration.

Respiration is a motor system essential for the survival of the individual and of the species. Because of its vital significance, studies on respiration often assume that breathing takes place independent of other motor systems. However, motor systems generating vocalization, coughing, sneezing, vomiting, as well as parturition, ejaculation, and defecation encompass abdominal pressure control, which involves changes in the respiratory pattern. The mesencephalic periaqueductal gray (PAG) controls all these motor systems. It determines the level setting of the whole body by means of its very strong projections to the ventromedial medullary tegmentum, but it also controls the cell groups that generate vocalization, coughing, sneezing, vomiting, as well as respiration. For this control, the PAG maintains very strong connections with the nucleus retroambiguus, which enables it to control abdominal and intrathoracic pressure. In this same context, the PAG also runs the pelvic organs, bladder, uterus, prostate, seminal vesicles, and the distal colon and rectum via its projections to the pelvic organ stimulating center and the pelvic floor stimulating center. These cell groups, via long descending projections, have direct control of the parasympathetic motoneurons in the sacral cord as well as of the somatic motoneurons in the nucleus of Onuf, innervating the pelvic floor. Respiration, therefore, is not a motor system that functions by itself, but is strongly regulated by the same systems that also control the other motor output systems.

Modulation of respiration is a prerequisite for survival of the individual and of the species. For example, respiration has to be adjusted in case of speech, strenuous exercise, laughing, crying, or sudden escape from danger. Respiratory centers in pons and medulla generate the basic respiratory rhythm or eupnea, but they cannot modulate breathing in the context of emotional challenges, for which they need input from higher brain centers. In simple terms, the prefrontal cortex integrates visual, auditory, olfactory, and somatosensory information and informs subcortical structures such as amygdala, hypothalamus, and finally the midbrain periaqueductal gray (PAG) about the results. The PAG, in turn, generates the final motor output for basic survival, such as setting the level of all cells in the brain and spinal cord. Best known in this framework is determining the level of pain perception. The PAG also controls heart rate, blood pressure, micturition, sexual behavior, vocalization, and many other basic motor output systems. Within this context, the PAG also changes the eupneic respiratory rhythm into a breathing pattern necessary for basic survival. This review examines the latest developments regarding of how the PAG controls respiration.

Respiration is not a separate motor system, but takes part in all basic survival mechanisms. This volume is the first that analyzes respiration in this framework.Respiration is one of the most basic motor activities crucial for survival of the individual. It is under total control of the central nervous system, which adjusts respiratory depth and frequency depending on the circumstances the individual finds itself. For this reason this volume not only reviews the basic control systems of respiration, located in the caudal brainstem, but also the higher brain regions, that change depth and frequency of respiration. Scientific knowledge of these systems is crucial for understanding the problems in the many patients suffering from respiratory failure.This well-established international series examines major areas of basic and clinical research within neuroscience, as well as emerging subfields.

Respiration is a motor system essential for the survival of the individual and of the species. Because of its vital significance, studies on respiration often assume that breathing takes place independent of other motor systems. However, motor systems generating vocalization, coughing, sneezing, vomiting, as well as parturition, ejaculation, and defecation encompass abdominal pressure control, which involves changes in the respiratory pattern. The mesencephalic periaqueductal gray (PAG) controls all these motor systems. It determines the level setting of the whole body by means of its very strong projections to the ventromedial medullary tegmentum, but it also controls the cell groups that generate vocalization, coughing, sneezing, vomiting, as well as respiration. For this control, the PAG maintains very strong connections with the nucleus retroambiguus, which enables it to control abdominal and intrathoracic pressure. In this same context, the PAG also runs the pelvic organs, bladder, uterus, prostate, seminal vesicles, and the distal colon and rectum via its projections to the pelvic organ stimulating center and the pelvic floor stimulating center. These cell groups, via long descending projections, have direct control of the parasympathetic motoneurons in the sacral cord as well as of the somatic motoneurons in the nucleus of Onuf, innervating the pelvic floor. Respiration, therefore, is not a motor system that functions by itself, but is strongly regulated by the same systems that also control the other motor output systems.

The somatic mutation burden in healthy white blood cells (WBCs) is not well known. Based on deep whole-genome sequencing, we estimate that approximately 450 somatic mutations accumulated in the nonrepetitive genome within the healthy blood compartment of a 115-yr-old woman. The detected mutations appear to have been harmless passenger mutations: They were enriched in noncoding, AT-rich regions that are not evolutionarily conserved, and they were depleted for genomic elements where mutations might have favorable or adverse effects on cellular fitness, such as regions with actively transcribed genes. The distribution of variant allele frequencies of these mutations suggests that the majority of the peripheral white blood cells were offspring of two related hematopoietic stem cell (HSC) clones. Moreover, telomere lengths of the WBCs were significantly shorter than telomere lengths from other tissues. Together, this suggests that the finite lifespan of HSCs, rather than somatic mutation effects, may lead to hematopoietic clonal evolution at extreme ages.

The nucleus retroambiguus (NRA) consists of premotor neurons in the caudal medulla. It is involved in expiration, vomiting, vocalization, and probably reproductive behavior by means of projections to distinct motoneuronal cell groups. Because no information is available about the NRA and its efferent pathways in primates, the present study examines NRA projections to the lumbosacral spinal cord in female rhesus monkeys. To identify the NRA, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected into the lumbosacral cord in three monkeys. To study the distribution of NRA axons in the lumbosacral cord, WGA-HRP injections were made into the NRA in seven monkeys. To identify motoneuronal cell groups receiving input from the NRA, the same seven monkeys also received cholera toxin subunit b (CTb) injections into different hindlimb, axial, and pelvic floor muscles. The results show that NRA neurons projecting to the lumbosacral cord are mainly located between 1 to 4 mm caudal to the obex. They send numerous axons to external oblique and pelvic floor motoneurons, whereas projections to iliopsoas and axial motoneurons are less numerous. The projections are bilateral, but show a clear contralateral predominance in the iliopsoas, axial, and pelvic floor motoneuronal cell groups. At the ultrastructural level, NRA-terminal profiles make asymmetrical contacts with labeled and unlabeled dendrites in these motoneuronal cell groups and contain large amounts of spherical and a few dense core vesicles. It is concluded that the NRA is well developed in the monkey and that there exists a direct pathway from the NRA to lumbosacral motoneurons in this species. The finding that the NRA projects to a somewhat different set of motoneuronal cell groups compared with other species fits the concept that it is not only involved in expiration-related activities but also in species specific receptive and submissive behavior. J. Comp. Neurol. 424: 233-250, 2000. (C) 2000 Wiley-Liss, Inc.

The urinary bladder muscle and its external urethral sphincter are innervated, respectively, by the parasympathetic preganglionic motoneurons in the sacral intermediolateral cell column and somatic motoneurons in Onuf's nucleus. Neurons coordinating the activity of these muscles during micturition and urinary continence are not located in the sacral cord but in two pontine regions, the medial (M)-region (or pontine micturition center) and the lateral (L)-region (or pontine storage center). The M-region excites the bladder muscle through projections to its motoneurons and inhibits the urethral sphincter through excitatory projections to sacral cord gamma-amino butyric acid (GABA)-immunoreactive interneurons, which, in turn, inhibit urethral sphincter motoneurons. The L-region, through direct projections, excites urethral sphincter motoneurons. The present study investigated whether there are interconnections between the M- and L-regions. Anterograde tracing injections in the M-region resulted in labeled fibers to the intermediolateral cell column containing bladder motoneurons but not to Onuf's nucleus. No specific projections were found to the L-regions or to the contralateral M-region. L-region injections resulted in distinct projections to the Onuf's nucleus but not to the sacral intermediolateral cell column. No specific projections were observed either to the M-region or to the contralateral L-region. In conclusion, the M- and L-regions have direct long fiber projections, respectively, to the motoneurons of the bladder muscle and the external urethral sphincter, but they do not influence one another through direct pathways. The results strongly suggest that the M- and L-regions represent separate functional systems that act independently.

Anatomical and physiological studies in rodent and cat have shown that distinct parts of the midbrain periaqueductal gray (FAG) are important for the estrogen dependent, female reproductive behavior. The present study gives a detailed overview of the estrogen receptor-alpha-immunoreactive (ER-IR) neurons in the FAG in the cat. ER-IR neurons were found throughout the rostrocaudal extent of the FAG and laterally adjacent tegmentum, but were most numerous at caudal levels. The lateral and dorsal PAG contained most ER-IR neurons, whereas moderate numbers were found dorsolaterally. In these areas, only very few ER-IR neurons were found near the border of the ependymal layer. Except for the rostral dorsal raphe nucleus, the central PAG contained only few ER-IR neurons. (C) 1998 Elsevier Science Ireland Ltd.

In a study on descending pathways from the nucleus retroambiguus (NRA) to hindlimb motoneurons (see accompanying paper), it appeared impossible, using data from the literature, to precisely determine which muscles were innervated by the motoneurons receiving the NRA fibers. This lack of data made it necessary to produce a detailed map of the lumbosacral motoneuronal cell groups in the cat. Therefore, 50 different muscles or muscle compartments of hindlimb, pelvic floor and lower back were injected with horseradish peroxidase (HRP) in 135 cases. The respective muscles were divided into ten groups: I, sartorius and iliopsoas; II, quadriceps; III, adductors; IV, hamstrings; V, gluteal and other proximal muscles of the hip; VI, posterior compartment of the distal hindlimb; VII, anterior compartment of the distal hindlimb; VIII, long flexors and intrinsic muscles of the foot; IX, pelvic floor muscles; and X, extensors of the lower back and tail. The L4-S2 segments were cut and incubated, and labeled motoneurons were counted and plotted. A new method was developed that made it possible, despite variations in size and segmental organization between the different cases, to compare the results of different cases. The results show that the spatial interrelationship between the hindlimb and pelvic floor lumbosacral motoneuronal cell groups remains constant. This finding enabled the authors to compose an accurate overall map of the location of lumbosacral motoneuronal cell groups. The general distribution of the motoneuronal cell groups is also discussed in respect to their dorsoventral, mediolateral, and rostrocaudal position within the lumbosacral ventral horn. (C) 1997 Wiley-Liss, Inc.

The nucleus retroambiguus (NRA) in the caudal medulla oblongata plays a role in expiration, vocalization, vomiting, and possibly lordosis. The present study tried to determine which structures, in turn, control the NRA. One cell group is the periaqueductal gray (FAG), which is considered to be the final integrator of defensive and aggressive behaviors, micturition, vocalization, and lordosis. Structures rostral to the FAG seem to bypass the NRA. With respect to the existence of cell groups caudal to the FAG projecting to the NRA, the situation is less clear. Therefore, in five adult female cats, injections of wheat germ agglutinin-horseradish peroxidase were centered on the NRA, and the resulting retrogradely labeled neurons were plotted. In the areas containing retrogradely labeled cells, the anterograde autoradiographic tracer [H-3]-leucine was injected in 66 cats. The combined results demonstrated that-NRA afferents not only originate from the FAG but also from specific cell groups in the pontine and medullary lateral tegmental field, i.e., the ventrolateral parabrachial nucleus, the nucleus Kolliker-Fuse, the retrotrapezoid nucleus, and the ventrolateral part of the medulla caudal to the facial nucleus including the Botzinger and pre-Botzinger complex and the periambigual region. Afferents also originate from the solitary nucleus and two cell groups in the ventral part of the medullary medial tegmental field, one at the level of facial nucleus and one just rostral to the hypoglossal nucleus. It can be concluded that many respiratory-related cell groups have direct access to the NRA. The cell groups in the medial tegmental field, which have not yet been found to play an important role in respiration, might-serve as relay for certain limbic system cell groups to reach the NRA in the context of specific emotional behavior. (C) 1996 Wiley-Liss, Inc.

Micturition is a spino-bulbo-spinal reflex. The bulbospinal part of this reflex is formed by the projections from the M-region, also called the pontine micturition center or Barrington's nucleus, to the preganglionic parasympathetic motoneurons in the sacral cord innervating the bladder. In respect to the spino-bulbar part of the micturition reflex, our group recently showed that the sacral cord projections to the brainstem terminate mainly in the periaqueductal gray (PAG). In this study it was investigated whether the PAG might serve as a link between the sacral cord and the M-region, by examining the possible connections using the tracers wheat germ-agglutin horseradish peroxidase and tritiated leucine. The results demonstrate that a specific circumscribed rostrocaudally oriented cell group within the ventrolateral PAG and parts of the dorsomedial PAG project specifically to the M-region. A concept is put forward in which specific parts of the PAG are involved in the control of micturition and that information concerning bladder filling is conveyed via the PAG to the M-region.

The lower urinary tract (LUT), which consists of the urinary bladder and its outlet, the urethra, is responsible for the storage and periodic elimination of bodily waste in the form of urine. The LUT is controlled by a complex set of peripheral autonomic and somatic nerves, which in turn are controlled through neural pathways in the spinal cord and brain. This influence of the central nervous system allows for the conscious control of the bladder, allowing the individual to choose an appropriate place to urinate. Defects in the CNS pathways that control the LUT can lead to incontinence, an embarrassing condition that affects over 200 million people worldwide. As a first step in understanding the neural control of the bladder, we will discuss the neuroanatomy of the LUT, focusing first on the peripheral neural pathways, including the sensory pathways that transmit information on bladder filling and the motoneurons that control LUT muscle contractility. We will also discuss the organization of the central pathways in the spinal cord and brainstem that are responsible for coordinating bladder activity, promoting continuous storage of urine except for a few short minutes per day when micturition takes place. To conclude, we will discuss current studies underway that aim to elucidate the higher areas of the brain that control the voluntary nature of micturition in higher organisms.

The lower urinary tract (LUT) has two functions: (1) the storage of waste products in the form of urine and (2) the elimination of those wastes through micturition. The LUT operates in a simple "on-off" fashion, either storing urine or releasing it during voiding. While this activity may seem simple, micturition is controlled by a complex set of peripheral neurons that are, in turn, coordinated by cell groups in the spinal cord, brainstem, and brain. When this careful coordination is interrupted, the control of the bladder is lost, resulting in incontinence or retention of urine. The purpose of this chapter is to review how the neural systems coordinating the activity of the lower urinary tract form neural circuits that are responsible for either maintaining continence (the storage reflex) or inducing micturition (the voiding reflex). We will also discuss the brain centers that enable higher organisms to voluntarily choose the time and place for voiding. Finally, we will discuss how defects in the pathways controlling micturition can lead to urinary incontinence and which treatments may normalize LUT function.

In cats, there exists a descending system that controls the posture necessary for mating behavior. A key role is played by the mesencephalic periaqueductal gray (PAG), which maintains strong specific projections to the nucleus retroambiguus located laterally in the most caudal medulla. The NRA, in turn, has direct access to motoneurons in the lumbosacral cord that produce the mating posture. This pathway is slightly different in males and females, but in females its strength fluctuates strongly depending on whether or not the cat is in heat. This way the PAG determines whether or not mating can take place. Via the PAG many other regions in the limbic system as well as in the prefrontal cortex and insula can influence mating behavior. In humans, the brain also controls responses to sexual stimulation as well as ejaculation in men and orgasm in women. Neuroimaging techniques show activations and de-activations but are not able to verify whether the PAG has a similar effect as in cats. PET-scanning results revealed that there is activation in the upper brainstem and cerebellum, as well as insula in men and in the somatomotor and somatosensory cortex in women. During sexual stimulation, but especially during ejaculation and orgasm there was strong de-activation mainly on the left side in the temporal lobe and ventral prefrontal cortex. These neuroimaging results show the importance of lowering the level of alertness regarding your immediate environment (left hemisphere) to have proper sexual behavior. (C) 2011 Elsevier Inc. All rights reserved.

The lower urinary tract (LUT) has two functions: (1) the storage of waste products in the form of urine and (2) the elimination of those wastes through micturition. The LUT operates in a simple “on–off” fashion, either storing urine or releasing it during voiding. While this activity may seem simple, micturition is controlled by a complex set of peripheral neurons that are, in turn, coordinated by cell groups in the spinal cord, brainstem, and brain. When this careful coordination is interrupted, the control of the bladder is lost, resulting in incontinence or retention of urine. The purpose of this chapter is to review how the neural systems coordinating the activity of the lower urinary tract form neural circuits that are responsible for either maintaining continence (the storage reflex) or inducing micturition (the voiding reflex). We will also discuss the brain centers that enable higher organisms to voluntarily choose the time and place for voiding. Finally, we will discuss how defects in the pathways controlling micturition can lead to urinary incontinence and which treatments may normalize LUT function.

The lower urinary tract (LUT), which consists of the urinary bladder and its outlet, the urethra, is responsible for the storage and periodic elimination of bodily waste in the form of urine. The LUT is controlled by a complex set of peripheral autonomic and somatic nerves, which in turn are controlled through neural pathways in the spinal cord and brain. This influence of the central nervous system allows for the conscious control of the bladder, allowing the individual to choose an appropriate place to urinate. Defects in the CNS pathways that control the LUT can lead to incontinence, an embarrassing condition that affects over 200 million people worldwide. As a first step in understanding the neural control of the bladder, we will discuss the neuroanatomy of the LUT, focusing first on the peripheral neural pathways, including the sensory pathways that transmit information on bladder filling and the motoneurons that control LUT muscle contractility. We will also discuss the organization of the central pathways in the spinal cord and brainstem that are responsible for coordinating bladder activity, promoting continuous storage of urine except for a few short minutes per day when micturition takes place. To conclude, we will discuss current studies underway that aim to elucidate the higher areas of the brain that control the voluntary nature of micturition in higher organisms.

Change of the basic respiratory rhythm (eupnea) is a pre-requisite for survival. For example, sudden escape from danger needs rapid shallow breathing, strenuous exercise requires tachypnea for sufficient supply of oxygen and a strong anxiety reaction necessitates gasping. Also for vocalization (and for speech in humans) an important mechanism for survival, respiration has to be changed. The caudal brainstem premotor respiratory centers need input from higher brain centers in order to change respiration according to the surrounding circumstances. One of the most important of such a higher brain centers is the midbrain periaqueductal gray (PAG). The PAG co-ordinates motor output, including respiratory changes based on input from limbic, prefrontal and anterior cingulate cortex regions. These areas integrate visual, auditory and somatosensory information in the context of basic survival mechanisms and relay the result to the PAG, which has access to respiratory control centers in the caudal brainstem. Through these pathways the PAG can change eupneic respiratory rhythm into the behavior necessary for that specific situation. We present data obtained from the cat and propose a functional framework for the breathing control pathways.

Keywords: motoneurons; bladder; sphincter; supraspinal control; pontine tegmentum; periaqueductal gray; preoptic area

Publisher Summary This chapter explains how the central nervous system controls micturition. It explains the spinal-brainstem-spinal micturition, the brain structures that have access to this circuit, and why certain lesions can cause urinary incontinence or the reverse, retention of urine. In order to properly control micturition, the central nervous system has to be informed how much urine the bladder contains, not only when the bladder is full, but at all times. Therefore, precise bladder filling information is conveyed from the bladder to the sacral cord. Incoming information to the central nervous system is always relayed by neurons in ganglia outside the central nervous system itself, in this case ganglion cells of the upper sacral cord. These sacral ganglion cells have peripheral and central fibers. The peripheral axons of the dorsal root pass through the pelvic and hypogastric nerves enter the bladder, where it contacts elements in the bladder wall that measure bladder filling. The organization of the sensory endings of the afferent fibers from the bladder is complex and only partly understood. Findings suggest that low threshold mechanoreceptors, sensitive to normal bladder filling, are mainly located in the muscular layers, and are directly sensitive to mechanical stretch and connected to myelinated (A-δ) fibers. Sacral cord ganglion cells also send peripheral axons through the pudendal nerve that enter the urethra. The sacral cord plays a central role in bladder and bladder sphincter control. There are two classes of fibers entering the sacral cord: thin myelinated A-δ fibers and unmyelinated C-fibers. Pontine micturition center (PMC), a group of neurons in the medial part of the dorsolateral pons, has complete control of micturition, because it is the only group of neurons that excites the detrusor muscle of the bladder and simultaneously inhibits its sphincter muscle, leading to complete so-called synergic micturition.

Many hundreds of thousands suffer spinal cord injuries leading to loss of sensation and motor function in the body below the point of injury. Spinal cord research has made some significant strides towards new treatment methods, and is a focus of many laboratories worldwide. In addition, research on the involvement of the spinal cord in pain and the abilities of nervous tissue in the spine to regenerate has increasingly been on the forefront of biomedical research in the past years."The Spinal Cord", a collaboration with the Christopher and Dana Reeve Foundation, is the first comprehensive book on the anatomy of the mammalian spinal cord. Tens of thousands of articles and dozens of books are published on this subject each year, and a great deal of experimental work has been carried out on the rat spinal cord. Despite this, there is no comprehensive and authoritative atlas of the mammalian spinal cord. Almost all of the fine details of spinal cord anatomy must be searched for in journal articles on particular subjects.This book addresses this need by providing both a comprehensive reference on the mammalian spinal cord and a comparative atlas of both rat and mouse spinal cords in one convenient source. The book provides a descriptive survey of the details of mammalian spinal cord anatomy, focusing on the rat with many illustrations from the leading experts in the field and atlases of the rat and the mouse spinal cord.The rat and mouse spinal cord atlas chapters include photographs of Nissl stained transverse sections from each of the spinal cord segments (obtained from a single unfixed spinal cord), detailed diagrams of each of the spinal cord segments pictured, delineating the laminae of Rexed and all other significant neuronal groupings at each level and photographs of additional sections displaying markers such as acetylcholinesterase (AChE), calbindin, calretinin, choline acetlytransferase, neurofilament protein (SMI 32), enkephalin, calcitonin gene-related peptide (CGRP), and neuronal nuclear protein (NeuN).The text provides a detailed account of the anatomy of the mammalian spinal cord and surrounding musculoskeletal elements. The major topics addressed are: development of the spinal cord; the gross anatomy of the spinal cord and its meninges; spinal nerves, nerve roots, and dorsal root ganglia; the vertebral column, vertebral joints, and vertebral muscles; blood supply of the spinal cord; cytoarchitecture and chemoarchitecture of the spinal gray matter; musculotopic anatomy of motoneuron groups; tracts connecting the brain and spinal cord; spinospinal pathways; sympathetic and parasympathetic elements in the spinal cord; neuronal groups and pathways that control micturition; and, the anatomy of spinal cord injury in experimental animals.The atlas of the rat and mouse spinal cord has the following features: photographs of Nissl stained transverse sections from each of 34 spinal segments for the rat and mouse; detailed diagrams of each of the 34 spinal segments for rat and mouse, delineating the laminae of Rexed and all other significant neuronal groupings at each level; and, alongside each of the 34 Nissl stained segments, there are additional sections displaying markers such as acetylcholinesterase, calbindin, calretinin, choline acetlytransferase, neurofilament protein (SMI 32), and neuronal nuclear protein (NeuN). All the major motoneuron clusters are identified in relation to the individual muscles or muscle groups they supply.

Background We used PET to study cortical activation during auditory stimulation and found sex differences in the human primary auditory cortex (PAC). Regional cerebral blood flow (rCBF) was measured in 10 male and 10 female volunteers while listening to sounds (music or white noise) and during a baseline (no auditory stimulation).Results and discussion We found a sex difference in activation of the left and right PAC when comparing music to noise. The PAC was more activated by music than by noise in both men and women. But this difference between the two stimuli was significantly higher in men than in women. To investigate whether this difference could be attributed to either music or noise, we compared both stimuli with the baseline and revealed that noise gave a significantly higher activation in the female PAC than in the male PAC. Moreover, the male group showed a deactivation in the right prefrontal cortex when comparing noise to the baseline, which was not present in the female group. Interestingly, the auditory and prefrontal regions are anatomically and functionally linked and the prefrontal cortex is known to be engaged in auditory tasks that involve sustained or selective auditory attention. Thus we hypothesize that differences in attention result in a different deactivation of the right prefrontal cortex, which in turn modulates the activation of the PAC and thus explains the sex differences found in the activation of the PAC.Conclusion Our results suggest that sex is an important factor in auditory brain studies.

There is a severe lack of knowledge regarding the brain regions involved in human sexual performance in general, and female orgasm in particular. We used [(15)O]-H(2)O positron emission tomography to measure regional cerebral blood flow (rCBF) in 12 healthy women during a nonsexual resting state, clitorally induced orgasm, sexual clitoral stimulation (sexual arousal control) and imitation of orgasm (motor output control). Extracerebral markers of sexual performance and orgasm were rectal pressure variability (RPstd) and perceived level of sexual arousal (PSA). Sexual stimulation of the clitoris (compared to rest) significantly increased rCBF in the left secondary and right dorsal primary somatosensory cortex, providing the first account of neocortical processing of sexual clitoral information. In contrast, orgasm was mainly associated with profound rCBF decreases in the neocortex when compared with the control conditions (clitoral stimulation and imitation of orgasm), particularly in the left lateral orbitofrontal cortex, inferior temporal gyrus and anterior temporal pole. Significant positive correlations were found between RPstd and rCBF in the left deep cerebellar nuclei, and between PSA and rCBF in the ventral midbrain and right caudate nucleus. We propose that decreased blood flow in the left lateral orbitofrontal cortex signifies behavioural disinhibition during orgasm in women, and that deactivation of the temporal lobe is directly related to high sexual arousal. In addition, the deep cerebellar nuclei may be involved in orgasm-specific muscle contractions while the involvement of the ventral midbrain and right caudate nucleus suggests a role for dopamine in female sexual arousal and orgasm.

This chapter focuses on the emotional motor system. It also discusses the somatic motor system in order to point out the similarities and differences between the two systems. The idea of the existence of an emotional motor system is primarily based on anatomical organization. The pathways of the somatic and emotional motor system are always separate until their termination on premotor interneurons or motoneurons. The function of the somatic and emotional motor system pathways is different. The emotional motor pathways play a role in basic survival behavior. The somatic or voluntary motor system, and especially its cortical parts, starts operating only after a relatively long time of processing environmental data, combined with information from the extensive memory banks in the various regions around the primary cortices. Moreover, the behavioral differences between animals and humans are not located in the emotional, but in the somatic motor system, which, as pointed out earlier, is nothing more than a tool of the emotional, or limbic system to fulfill its needs. In that respect, humans differ only slightly from other animals.