A test for constant natural frequencies in electrocortical activity under lateral hypothalamic control

An initial test for a theory of lateral hypothalamic regulation of electrocortical activity is undertaken. The theory supposes lateral hypothalamic input directly or indirectly damps telencephalic resonances involving linear wave phenomena, enabling this pathway to act as parametric control of information processing in cortical neural networks. Relative changes in left and right electrocortical power spectra are used to test for the presence of resonant modes with constant natural frequencies in conditions of asymmetrical damping, following unilateral lesion of the lateral hypothalamus. Natural frequency values for the modes clustered about center frequencies in the EEG band are obtained. This method has the advantage of minimising the effects of time-variation and the recorded signal's distortion from the electrocortical local spatial average, but limits consideration to five dominant modes of resonance. The uncertainty of true model order, and errors in curve-fitting impose limitations on the test.     

Amplitude and phase relations of electrocortical waves regulated by transhypothalamic dopaminergic neurones: A test for a linear theory

We have previously proposed that electrocortical activity (EEG) arises as a manifestation of linear waves generated by resonance among telencephalic neurones, and that this activity is controlled in part by ascending neurones from the brain-steim, which regulate the damping of each resonance. The presentexperiments focus on a specific class of ascending neurones, the mesotelencephalic dopaminergic cells, because these cells are thought to mediate important psychological effects, and are conveniently subject to selective lesion. A critical test of the theory is undertaken, by performing selective unilateral lesion, assessing the changes in the power spectrum of the EEG attributable to lesion, and determining whether the changes in phase of the EEG correspond to that predicted from the changes in power. Results support the theory, although the model order applicable in these experiments is inadequate. The consequences of these findings for automata theory, linear network theory and their application to mammalian brains are briefly discussed.     

Organization of histamine-containing neurons in the brain of the crested newt,Triturus carnifex

The distribution of immunoreactivity for histamine was studied in the brain of the urodele Triturus carnifex using the indirect immunofluorescence method. Histamine-immunoreactive cell bodies were localized in the caudal hypothalamus within the dorsolateral walls of the infundibular recesses. These immunoreactive cell bodies were pear-shaped, bipolar and frequently of the cerebrospinal-fluid-contacting type. Histaminergic nerve fibers were detected in almost all parts of the brain. Dense innervation was seen in the telencephalic medial pallium and ventral striatum, the neuropil of the preoptic area, the septum, the paraventricular organ, the posterior commissure, the caudal hypothalamus, the ventral and lateral mesencephalic tegmentum. Medium density innervation was observed in the lateral mesencephalic tegmentum and optic tectum. Poor innervation was present in the telencephalic dorsal pallium and in the central gray of the medulla oblongata. Few fibers occurred in the olfactory bulbs and in the telencephalic lateral pallium. Double immunofluorescence staining, using an antibody against tyrosine hydroxylase, showed that histamine-immunostained somata and those containing tyrosine-hydroxylase-like immunoreactivity were co-distributed in the tuberal hypothalamus. No co-occurrence of histamine-like and tyrosine hydroxylase-like immunostaining was seen in the same neuron. The pattern of histamine-immunoreactive neurons in the newt was similar to that described in other vertebrates. Our observations, carried out on the apparently simplified brain of the newt confirm that the basic histaminergic system is well conserved throughout vertebrates.     

Thalamocortical axons are influenced by chemorepellent and chemoattractant activities localized to decision points along their path

Thalamocortical axons (TCAs), which originate in dorsal thalamus, project ventrally in diencephalon and then dorsolaterally in ventral telencephalon to their target, the neocortex. To elucidate potentially key decision points in TCA pathfinding and hence the possible localization of guidance cues, we used DiI-tracing to describe the initial trajectory of TCAs in mice. DiI-labeled TCAs extend ventrally on the lateral surface of ventral thalamus. Rather than continuing this trajectory onto the lateral surface of the hypothalamus, TCAs make a sharp lateral turn into ventral telencephalon. This behavior suggests that the hypothalamus is repulsive and the ventral telencephalon attractive for TCAs. In support of this hypothesis, we find that axon outgrowth from explants of dorsal thalamus is biased away from hypothalamus and toward ventral telencephalon when cocultured at a distance in collagen gels. The in vivo DiI analysis also reveals a broad cluster of retrogradely labeled neurons in the medial part of ventral telencephalon positioned within or adjacent to the thalamocortical pathway prior to or at the time TCAs are extending through it. The axons of these neurons extend into or through dorsal thalamus and appear to be coincident with the oppositely extending TCAs. These findings suggest that multiple cues guide TCAs along their pathway from dorsal thalamus to neocortex: TCAs may fasciculate on the axons of ventral telencephalic neurons as they extend through ventral thalamus and the medial part of ventral telencephalon, and chemorepellent and chemoattractant activities expressed by hypothalamus and ventral telencephalon, respectively, may cooperate to promote the turning of TCAs away from hypothalamus and into ventral telencephalon.     

Chronic stress increases the reactivity of central depressor mechanisms]

The activity of noradrenergic system of lateral hypothalamus and hemodynamics were studied during acute restraint in chronically stressed and control rats. Arterial blood pressure in rest was negatively proportional to basal norepinephrine concentration in dialysate of lateral hypothalamus. Animals with high increase of norepinephrine levels in dialysate during acute stress had rapid return of arterial blood pressure to basal values while stress-induced hypertension in the beginning of restraint was the same as in rats with low increase of norepinephrine levels. Data obtained show the depressor role of noradrenergic system of lateral hypothalamus. The enhanced reactivity of noradrenergic depressor system may be one of the mechanisms providing cardiovascular adaptation to stress.     

Impact modeling of gymnastic back-handsprings and dive-rolls in children

This study was to determine estimates of the stiffness and damping properties of the wrist, and shoulder in children by examining wrist impacts on the outstretched hand in selected gymnastic activities. The influence of age, mass, and wrist and torso impact velocity on the stiffness and damping properties were also examined. Fourteen young gymnasts (ages 8 to 15 yrs) were videotaped while performing back-handspring trials or dive-rolls. Kinematic and ground reaction analysis provided input for computer simulation of the body as a rheological model with appropriate stiffness and damping. A significant positive linear relationship was obtained between wrist damping in dive rolls and age, mass, and wrist and torso impact velocity, while shoulder damping in the back-handsprings had a significant positive linear relationship with body mass. This new information on stiffness and damping at the shoulder and the wrist in children enables realistic mathematical modeling of children's physical responses to hand impact in falls. This is significant because modeling studies can now be used as an alternative to epidemiological studies to evaluate measures aimed at reducing injuries in gymnastics and other activities involving impact to the upper extremity.     

Neuroanatomical Distribution and Variations across the Reproductive Cycle of Aromatase Activity and Aromatase-Immunoreactive Cells in the Pied Flycatcher (Ficedula hypoleuca)

The anatomical distribution and seasonal variations in aromatase activity and in the number of aromatase-immunoreactive cells were studied in the brain of free-living male pied flycatchers (Ficedula hypoleuca). A high aromatase activity was detected in the telencephalon and diencephalon but low to negligible levels were present in the optic lobes, cerebellum, and brain stem. In the diencephalon, most aromatase-immunoreactive cells were confined to three nuclei implicated in the control of reproductive behaviors: the medial preoptic nucleus, the nucleus of the stria terminalis, and the ventromedial nucleus of the hypothalamus. In the telencephalon, the immunopositive cells were clustered in the medial part of the neostriatum and in the hippocampus as previously described in another songbird species, the zebra finch. No immunoreactive cells could be observed in the song control nuclei. A marked drop in aromatase activity was detected in the anterior and posterior diencephalon in the early summer when the behavior of the birds had switched from defending a territory to helping the female in feeding the nestlings. This enzymatic change is presumably controlled by the drop in plasma testosterone levels observed at that stage of the reproductive cycle. No change in enzyme activity, however, was seen at that time in other brain areas. The number of aromatase-immunoreactive cells also decreased at that time in the caudal part of the medial preoptic nucleus but not in the ventromedial nucleus of the hypothalamus (an increase was even observed), suggesting that differential mechanisms control the enzyme concentration and enzyme activity in the hypothalamus. Taken together, these data suggest that changes in diencephalic aromatase activity contribute to the control of seasonal variations in reproductive behavior of male pied flycatchers but the role of the telencephalic aromatase in the control of behavior remains unclear at present.     

Inference of a stable dispersion relation for electrocortical activity controlled by the lateral hypothalamus

A second test is undertaken for a theory of linear wave motion in electrocortical waves, under lateral hypothalamic control via regulation of damping. This test invokes a general property of linear systems, namely that wave motion with characteristic natural frequencies implies fixed phase velocities associated with each wavelength, independent of the changes in hypothalamic input. A means of testing the invariance of this dispersion relation at the point of recording is derived from a simplified biophysical model for waves in a dipole layer. The method avoids some problems implicit in direct spatio-temporal wave analysis. Results confirm that the model under test is internally consistent, and is also consistent with other findings concerning the origin and spatial nature of the EEG.     

Electrical activity of the lateral hypothalamus related to food-procuring movements of rats

On freely moving albino rats we demonstrated that, when fast food-procuring movements are performed, the mass electrical activity of the lateral hypothalamus (LH) is suppressed 1.6–2.0 sec before the movement beginning recorded with a photoelectrical device. Videorecording of the movements and recording of the spike activity of LH units showed that the latter are activated 1.0–0.1 sec before the movement initiation. The LH is considered a motivation-related structure, which serves as a source providing an increase in the excitability of the structures involved in the control of food-procuring movements and, further on, supporting this increased excitability. The LH is also a component of the mechanisms providing formation of the motor program. The role of the LH in the ensemble of motor centers, which organize and control voluntary movements, is discussed.     

Changes in the mechanical properties of the trunk in low back pain may be associated with recurrence

Exercise is one of the few effective treatments for LBP. Although exercise is often based on the premise of reduced spinal stiffness, trunk muscle adaptation may increase stiffness. This study developed and validated a method to assess trunk stiffness and damping, and tested these parameters in 14 people with recurring LBP and 17 pain-free individuals. Effective trunk stiffness, mass and damping were estimated with the trunk modeled as a linear second-order system following trunk perturbation. Equal weights (12–15% body weight) were attached to the front and back of the trunk via pulleys such that the trunk could move freely and no muscle activity was required to hold the weights. The trunk was perturbed by the unexpected release of one of the weights. Trunk kinematics and cable force were used to estimate system properties. Reliability was assessed in 10 subjects. Trunk stiffness was greater in recurrent LBP patients (forward perturbation only), but damping was lower (both directions) than healthy controls. Estimates were reliable and validated by accurately estimated mass. Contrary to clinical belief, trunk stiffness was increased, not reduced, in recurrent LBP, most likely due to augmented trunk muscle activity and changes in reflex control of trunk muscles. Although increased stiffness may aid in the protection of spinal structures, this may have long-term consequences for spinal health and LBP recurrence due to compromised trunk dynamics (decreased damping).     

Role of the lateral hypothalamus and prefrontal cortex in organization of voluntary movements

Roles of the lateral hypothalamus and prefrontal cortex in organization and control of automatized food-procuring movements were studied in rats under conditions of unrestrained behavior with the use of video- and photorecording techniques, destruction of the brain structures, and recording of single neuron impulse responses. The lateral hypothalamus is considered a link in the control system for food-procuring movements, which provides formation of the motor program. The role of the prefrontal cortex is regarded as related to programing and initiation of food-procuring movements and current control of efficiency of their performance. Positions of the lateral hypothalamus and prefrontal cortex within an ensemble of the motor centers, which organizes voluntary movements, are discussed.     

The Gsh2 homeodomain gene controls multiple aspects of telencephalic development

Homeobox genes have recently been demonstrated to be important for the proper patterning of the mammalian telencephalon. One of these genes is Gsh2, whose expression in the forebrain is restricted to the ventral domain. In this study, we demonstrate that Gsh2 is a downstream target of sonic hedgehog and that lack of Gsh2 results in profound defects in telencephalic development. Gsh2 mutants have a significant decrease in the expression of numerous genes that mark early development of the lateral ganglionic eminence, the striatal anlage. Accompanying this early loss of patterning genes is an initial expansion of dorsal telencephalic markers across the cortical-striatal boundary into the lateral ganglionic eminence. Interestingly, as development proceeds, there is compensation for this early loss of markers that is coincident with a molecular re-establishment of the cortical-striatal boundary. Despite this compensation, there is a defect in the development of distinct subpopulations of striatal neurons. Moreover, while our analysis suggests that the migration of the ventrally derived interneurons to the developing cerebral cortex is not significantly affected in Gsh2 mutants, there is a distinct delay in the appearance of GABAergic interneurons in the olfactory bulb. Taken together, our data support a model in which Gsh2, in response to sonic hedgehog signaling, plays a crucial role in multiple aspects of telencephalic development.     

Sex differences in cell migration in the preoptic area/anterior hypothalamus of mice

The preoptic area/anterior hypothalamus (POA/AH) sits as a boundary region rostral to the classical diencephalic hypothalamus and ventral to the telencephalic septal region. Numerous studies have pointed to the region's importance for sex‐dependent functions. Previous studies suggested that migratory guidance cues within this region might be particularly unique in their diversity. To better understand the early development and differentiation of the POA/AH, cytoarchitectural, birthdate, immunocytochemical, and cell migration studies were conducted in vivo and in vitro using embryonic C57BL/6J mice. A medial preoptic nucleus became discernible using Nissl stain in males and females between embryonic days (E) E15 and E17. Cells containing immunoreactive estrogen receptor‐α were detected in the POA/AH by E13, and increased in number with age in both sexes. From E15 to E17, examination of the radial glial fiber pattern by immunocytochemistry confirmed the presence of dual orientations for migratory guidance ventral to the anterior commissure (medial‐lateral and dorsal‐ventral) and uniform orientation more caudally (medial‐lateral). Video microscopy studies followed the migration of DiI‐labeled cells in coronal 250‐μm brain slices from E15 mice maintained in serum‐free media for 1–3 days. Analyses showed significant migration along a dorsal‐ventral orientation in addition to medial‐lateral. The video analyses showed significantly more medial‐lateral migration in males than females in the caudal POA/AH. In vivo, changes in the distribution of cells labeled by the mitotic indicator bromodeoxyuridine (BrdU) suggested their progressive migration through the POA/AH. BrdU analyses also indicated significant movement from dorsal to ventral regions ventral to the anterior commissure. The significant dorsal‐ventral migration of cells in the POA/AH provides additional support for the notion that the region integrates developmental information from both telencephalic and diencephalic compartments. The sex difference in the orientation of migration of cells in the caudal POA/AH suggests one locus for the influence of gonadal steroids in the embryonic mouse forebrain. © 1999 John Wiley & Sons, Inc. J Neurobiol 41: 252–266, 1999     

BMP signaling is required locally to pattern the dorsal telencephalic midline

BMPs have been proposed to pattern the medial-lateral axis of the telencephalon in a concentration-dependent manner, thus helping to subdivide the embryonic telencephalon into distinct forebrain regions. Using a CRE/loxP genetic approach, we tested this hypothesis by disrupting the Bmpr1a gene in the telencephalon. In mutants, BMP signaling was compromised throughout the dorsal telencephalon, but only the most dorsalmedial derivative, the choroid plexus, failed to be specified or differentiate. Choroid plexus precursors remained proliferative and did not adopt the fate of their lateral telencephalic neighbors. These results demonstrate that BMP signaling is required for the formation of the most dorsal telencephalic derivative, the choroid plexus, and that BMP signaling plays an essential role in locally patterning the dorsal midline. Our data fail to support a more global, concentration-dependent role in specifying telencephalic cell fates.     

BRAIN DOPAMINE-β-HYDROXYLASE: REGIONAL DISTRIBUTION AND EFFECTS OF LESIONS AND 6-HYDROXY-DOPAMINE ON ACTIVITY

Abstract— A modification of a specific and sensitive radioassay was used to measure dopamine-β-hydroxylase (DBH) (EC 1.14.2.1) in various regions of the rat CNS. Highest activity was found in the hypothalamus. Relative to activity in the hypothalamus (= 100 per cent), activity in brainstem was 80 per cent, in sensory motor cortex 55 per cent, in caudate nucleus 32 per cent, and in cervical spinal cord 30 per cent. Two to three weeks after a unilateral electrolytic lesion of the lateral hypothalamus, activity of DBH in the ipsilateral cerebral cortex fell to 17 per cent of control values without changes in activity ipsi- or contra-laterally in the brainstem. Thalamic lesions did not affect DBH activity. In cerebral cortex contralateral to the hypothalamic lesion, enzymic activity rose 30 per cent. After intracisternal administration of 6-hydroxy-dopamine (6-OH-DA), cortical DBH activity fell to 20 per cent of control values. Reserpine (3 mg/kg subcutaneously for 3 days) did not increase the activity of DBH in brain regions but did increase the activity of DBH in adrenal gland 200 per cent. Our results suggest that: (a) DBH is widely distributed in neurons in CNS with a regional pattern of activities that appears to parallel the Jevels of norepinephrine; (b) DBH activity in the cerebral cortex depends on the integrity of structures (e.g. medial forebrain bundle) in lateral hypothalamus; (c) DBH in brain areas lacking cell bodies of nore- pinephrine-neurons (e.g. cerebral cortex) is contained in norepinephrine-containing axon terminals and (d) the activity of DBH in brain is not increased by reserpine under conditions that provoke marked increase of DBH activity in the adrenal gland.     

Cell cycle progression

In this paper we consider cell cycle models for which the transition operator for the evolution of birth mass density is a simple, linear dynamical system with a stochastic perturbation. The convolution model for a birth mass distribution is presented. Density functions of birth mass and tail probabilities in n-th generation are calculated by a saddle-point approximation method. With these probabilities, representing the probability of exceeding an acceptable mass value, we have more control over pathological growth. A computer simulation is presented for cell proliferation in the age-dependent cell cycle model. The simulation takes into account the fact that the age-dependent model with a linear growth is a simple linear dynamical system with an additive stochastic perturbation. The simulated data as well as the experimental data (generation times for mouse L) are fitted by the proposed convolution model.     

Fate of the anterior neural ridge and the morphogenesis of the xenopus forebrain

The fate of the anterior neural ridge was studied by following the relative movements of simultaneous spot applications of DiI and DiO from stage 15 through stage 45. These dye movements were mapped onto the neuroepithelium of the developing brain whose shape was gleaned from whole-mount in situs to neural cell adhesion molecule and dissections of the developing nervous system. The result is a model of the cell movements that drive the morphogenesis of the forebrain. The midanterior ridge moves inside and drops down along the most anterior wall of the neural tube. It then pushes forward a bit, rotates ventrally during forebrain flexing, and gives rise to the chiasmatic ridge and anterior hypothalamus. The midanterior plate drops, forming the floor of the forebrain ventricle, and, keeping its place behind the ridge, it gives rise to the posterior hypothalamus or infundibulum. The midlateral anterior ridge slides into the lateral anterior wall of the neural tube and stretches laterally into the optic stalk and retina, and then rotates into a ventral position. The lateral anterior ridge converges to the most anterior part of the dorsal midline during neural tube closure, then rotates anteriorly, and gives rise to telencephalic structures. Whole-mount bromodeoxyuridine labeling at these stages showed that cell division is widespread and relatively uniform throughout the brain during the late neurula and early tailbud stages, but that during late tailbud stages cell division becomes restricted to specific proliferative zones. We conclude that the early morphogenesis of the brain is carried out largely by choreographed cell movements and that later morphogenesis depends on spatially restricted patterns of cell division. © 1995 John Wiley & Sons, Inc.     

Plasma Osmolality Predicts Extracellular Fluid Catechol Concentrations in the Lateral Hypothalamus

The lateral hypothalamus has an important role in regulating food and water intake. We have investigated the endogenous release of monoamines from the lateral hypothalamus during manipulations of plasma osmolality and circulating volume. Adult male Sprague-Dawley rats implanted with carbon paste in vivo electrochemical (EC) electrodes in the lateral hypothalamus were placed on a 72-h water deprivation schedule. Although the carbon paste EC electrode has an intrinsically ambiguous signal in which changes in ascorbic acid may appear as changes in catechol concentrations, pharmacologic studies in lateral hypothalamus indicated that the electrode most likely measured norepinephrine and possibly epinephrine. On the test day, the EC electrodes were scanned with linear sweep voltammetry from -0.2 to +0.4 V at a rate of 5 mV/s. Semiderivative signal processing showed catechol and hydroxyindole peaks at +0.11 and +0.23 V, respectively. Baseline recordings were made prior to rats drinking distilled water, 10% sucrose, 5% dextrose, 0.30% NaCl, 0.90% NaCl, or 10% d-mannitol. To control for the act of drinking, other implanted dehydrated rats were intraperitoneally injected with 5% dextrose, 0.30% NaCl, or 0.90% NaCl. To dissociate the effects of osmolality and circulating volume on the EC response, hydrated rats implanted with EC electrodes were subcutaneously injected with 12% NaCl or intraperitoneally injected with 35% polyethylene glycol. Other rats subjected to water deprivation and osmotic challenges were decapitated and trunk blood was collected for measurements of plasma osmolality and hematocrit. Similar experiments were conducted using homozygous Brattleboro rats which lack arginine vasopressin (AVP) but which preserve normal plasma osmolality with prodigious drinking.(ABSTRACT TRUNCATED AT 250 WORDS)     

A holistic model for an internal representation to control the movement of a manipulator with redundant degrees of freedom

The paper proposes a model for the control of a multisegmented manipulator with redundant degrees of freedom. On the basis of an earlier model, the so-called MMC net, a simplified version is proposed here which has several advantages. First, it can easily be scaled up for the 3D case. Second, for the linear version a complete convergence proof is possible. Third, an easy way of implementing a damping parameter is shown. Fourth, the properties of the earlier model are unchanged, namely versatile control of the redundant system, immediate change from direct kinematics to inverse kinematics or any mixed control task, as well as robustness in the case of singularities. Received: 4 October 1997 / Accepted in revised form: 26 August 1998     

2010 Carl Ludwig Distinguished Lectureship of the APS Neural Control and Autonomic Regulation Section: Central neural pathways for thermoregulatory cold defense

Central neural circuits orchestrate the homeostatic repertoire to maintain body temperature during environmental temperature challenges and to alter body temperature during the inflammatory response. This review summarizes the research leading to a model representing our current understanding of the neural pathways through which cutaneous thermal receptors alter thermoregulatory effectors: the cutaneous circulation for control of heat loss, and brown adipose tissue, skeletal muscle, and the heart for thermogenesis. The activation of these effectors is regulated by parallel but distinct, effector-specific core efferent pathways within the central nervous system (CNS) that share a common peripheral thermal sensory input. The thermal afferent circuit from cutaneous thermal receptors includes neurons in the spinal dorsal horn projecting to lateral parabrachial nucleus neurons that project to the medial aspect of the preoptic area. Within the preoptic area, warm-sensitive, inhibitory output neurons control heat production by reducing the discharge of thermogenesis-promoting neurons in the dorsomedial hypothalamus. The rostral ventromedial medulla, including the raphe pallidus, receives projections form the dorsomedial hypothalamus and contains spinally projecting premotor neurons that provide the excitatory drive to spinal circuits controlling the activity of thermogenic effectors. A distinct population of warm-sensitive preoptic neurons controls heat loss through an inhibitory input to raphe pallidus sympathetic premotor neurons controlling cutaneous vasoconstriction. The model proposed for central thermoregulatory control provides a platform for further understanding of the functional organization of central thermoregulation.