Calretinin Neurons in the Rat Suprachiasmatic Nucleus.

The hypothalamic suprachiasmatic nucleus (SCN), a circadian pacemaker, is present in all mammalian brains. It has a complex organization of peptide-containing neurons that is similar among species, but calcium-binding proteins are expressed variably. Neurons containing calretinin have been described in the SCN in a number of species but not with association to circadian function.

The suprachiasmatic nucleus and the circadian timing system.

The circadian timing system (CTS) in mammals may be defined as a network of interconnected diencephalic structures that regulate the timing of physiological processes and behavioral state. The central feature of the CTS is the suprachiasmatic nucleus (SCN) of the hypothalamus, a self-sustaining circadian oscillator entrained by visual afferents, input from other brain and peripheral oscillators. The SCN was first noted as a distinct component of the hypothalamus during the late nineteenth century and recognized soon after as a uniform feature of the mammalian and lower vertebrate brain.

Innervation of ventricular and periventricular brain compartments.

Synaptic transmission is divided into two broad categories on the basis of the distance over which neurotransmitters travel. Wiring transmission is the release of transmitter into synaptic clefts in close apposition to receptors. Volume transmission is the release of transmitters or modulators over varying distances before interacting with receptors.

In vivo assessment of brain monoamine systems in parkin gene carriers: a PET study.

PET studies in parkin-linked parkinsonism have generally been performed to assess striatal dopaminergic dysfunction and very little is known about the involvement of other monoaminergic structures in these patients. Measurements of (18)F-dopa uptake into serotonergic and noradrenergic structures provide an indication of the functional integrity of these nerve terminals. We used (18)F-dopa PET to assess changes in brain monoaminergic function associated with parkin mutations.

Basal forebrain atrophy is a presymptomatic marker for Alzheimer's disease.

Background: Alzheimer's disease (AD) is the most common degenerative neurologic disorder. The onset of symptoms is insidious and follows a long period of progression of an asymptomatic pathology that proceeds in a precise anatomic and temporal sequence. Recent studies with quantitative magnetic resonance imaging techniques have shown the localization of the in vivo pathology of AD and its antecedent, mild cognitive impairment.

Extrastriatal monoamine neuron function in Parkinson's disease: an 18F-dopa PET study.

The early motor manifestations of Parkinson's disease (PD) reflect degeneration of nigrostriatal dopamine neurons projecting to the caudal putamen. However, extrastriatal dopamine and other monoamine systems are also involved, particularly in later disease. We used (18)F-dopa PET in a cross-sectional study to characterize extrastriatal monoamine neuronal dysfunction in PD.

Gamma Knife thalamotomy for essential tremor.

Objectives: The purpose of this study was to evaluate the results following Gamma Knife thalamotomy (GKT) for medically refractory essential tremor in a series of patients in whom open surgical techniques were not desirable.

Methods: Thirty-one patients underwent GKT for disabling essential tremor after medical therapy had failed. Their mean age was 77 years.

Suprachiasmatic nucleus in sleep-wake regulation.

The evolution of animals is a consequence of selective specialization of cells, tissues, functional systems, and behavior. The objective of all life is successful reproduction and maintenance of the species. In order to accomplish this, all animals have evolved a division of behavior into two fundamental behavioral states: one characterized by the elaboration of adaptive behavior (activity) and the other by rest and behavioral quiescence (rest).

Grooved pegboard test as a biomarker of nigrostriatal denervation in Parkinson's disease.

Recent pharmacotherapy trials in Parkinson's disease (PD) using dopaminergic neuroimaging as outcome parameter failed to show significant relationships between imaging and clinical results. One possible explanation is that there is a non-linear relationship between striatal denervation and motor performance reflecting a statistical "floor" effect in the imaging data with advanced disease. Both the motor manifestations and the striatal dopamine denervation of idiopathic PD, however, are typically asymmetric and more meaningful associations may be found by comparing data from the least denervated striatum with motor performance in the corresponding body side.

Selective hyposmia and nigrostriatal dopaminergic denervation in Parkinson's disease.

Olfactory dysfunction is a frequent and early feature of Parkinson's disease (PD), often preceding the motor symptoms by several years. Assessment of olfactory deficits may be used in the diagnostic assessment of PD. In this study we investigated the relationship between selective deficits in smell identification and nigrostriatal dopaminergic denervation in patients with PD.

Diurnal variation in regional brain glucose metabolism in depression.

Background: This study compared diurnal variation in mood and regional cerebral metabolic rate of glucose (rCMRglc) in depressed and healthy subjects.

Methods: Depressed and healthy subjects were investigated using [18F]-fluoro-deoxyglucose positron emission tomography scans during morning and evening wakefulness. All subjects completed subjective mood ratings at both times of day.

Lesions of suprachiasmatic nucleus efferents selectively affect rest-activity rhythm.

The suprachiasmatic nucleus (SCN) of the hypothalamus controls circadian rhythms in behavioral, neuroendocrine and physiological functions. In this study, we test the hypothesis that caudal SCN efferents to the subparaventricular zone (SPVZ) control the rhythm in rest-activity (R-A) through projections on posterior hypothalamic area arousal systems (PHA). Small electrolytic lesions of the ventral SPVZ cause a selective loss of the circadian R-A rhythm, sparing the core body temperature rhythm.

Cognitive correlates of alterations in acetylcholinesterase in Alzheimer's disease.

We recently reported findings of modest loss of cortical acetylcholinesterase (AChE) activity in patients with overall mild Alzheimer's disease (AD) using N-[11C]methyl-pi-peridin-4-yl propionate ([11C]PMP) AChE positron emission tomography (PET). To determine cognitive correlates of in vivo cortical AChE activity in patients with mild to moderate AD (n=15), and in normal controls (NC, n=12) using [11C]PMP AChE PET imaging. Mean cortical AChE activity in the AD subjects was mildly reduced (-11.

Predictive models of postural control based on electronic force platform measures in patients with Parkinson's disease.

The human postural control system is difficult to quantify since it seems to be subject to both deterministic forces as well as stochastic effects. The attempt made in this paper is to study postural control under quiet stance on the one hand, and by engaging the brain through a fluency test, on the other. A Kistler electronic platform is the vehicle by way of which we gather observations in the form of center of pressure (COP) trajectories.

Regional brain glucose metabolism during morning and evening wakefulness in humans: preliminary findings.

Study Objectives: The mechanisms that maintain wakefulness across the day, in the face in increasing sleep drive, are largely unknown. The goal of this pilot study was to examine regional relative brain glucose metabolism during morning and evening wakefulness in healthy humans.

Design: [18F]-fluorodeoxyglucose positron emission tomography scans were conducted during quiet wakefulness in the morning and in the evening.

The suprachiasmatic nucleus and sleep-wake regulation.

Human behavior is organized into 24-hour cycles that are typically composed of about 16 hours of wakefulness and about 8 hours of sleep. Sleep is an essential behavior and is critical for maintaining normal adaptive waking behavior. Both sleep and wake are initiated and maintained by separate and specific neural systems.

Serotonin innervation of the primate suprachiasmatic nucleus.

The suprachiasmatic nucleus (SCN) in rodents receives a dense innervation from serotonin neurons of the midbrain raphe. This projection overlaps the terminal field of the retinohypothalamic tract in the SCN core, the central part of the nucleus characterized by a population of vasoactive intestinal polypeptide (VIP)-containing neurons. To determine whether a similar pathway is present in primates, we carried out an immnunocytochemical investigation of the primate SCN using antisera against either serotonin (monkey) or the serotonin transporter (human).

Cortical cholinergic function is more severely affected in parkinsonian dementia than in Alzheimer disease: an in vivo positron emission tomographic study.

Background: Pathology reports have shown that cholinergic forebrain neuronal losses in parkinsonian dementia (PDem) are equal to or greater than those in Alzheimer disease (AD). We hypothesized that patients with PDem would have cholinergic deficits that were similar to or greater than those of patients with AD.

Objective: To determine in vivo cortical acetylcholinesterase (AChE) activity in healthy control subjects and in patients with mild AD, PDem, and Parkinson disease without dementia using AChE positron emission tomography.

Pattern of hypocretin (orexin) soma and axon loss, and gliosis, in human narcolepsy.

Human narcolepsy is correlated with a greatly reduced number of hypocretin (orexin) containing neurons and axons, and an elevated level of hypothalamic gliosis. We now report that the percentage loss of Hcrt cells and percentage elevation of GFAP staining are variable across forebrain and brain-stem nuclei, and are maximal in the posterior and tuberomammillary hypothalamic region. Regional gliosis and percent loss of hypocretin axons in narcoleptics are not correlated with regional hypocretin cell soma density in normals or with regional percent soma loss in narcoleptics.

Monoamine neuron innervation of the normal human brain: an 18F-DOPA PET study.

18F-DOPA positron emission tomography (PET) has been used for two decades to study the organization and pathology of the striatal dopamine system in the human brain, particularly in Parkinson's disease. High resolution 3D PET allows a more detailed analysis than previously available and was employed in this study to determine the regional uptake of 18F-DOPA in control brain. Eleven healthy volunteers underwent 18F-DOPA PET with a region of interest (ROI) study performed using individual volumetric MRI's coregistered to the PET ADD image.

Organization of midbrain dopamine systems and the pathophysiology of Parkinson's disease.

Understanding of the pathophysiology of Parkinson disease (PD) has advanced rapidly over the last two decades through basic and clinical studies using modern neuroanatomical, clinical assessment, neuropathological and functional brain imaging methods. Two interacting processes determine the development of functional impairment, neuronal degeneration with selective denervation of specific regions and compensatory responses, which oppose the effects of denervation. The clinical manifestations of PD, at least in early stages, reflect selective degeneration of dopamine neurons in the substantia nigra projecting through the nigrostriatal pathway to the caudal putamen with compensatory changes in this and related systems.

Plasticity of the nigropallidal pathway in Parkinson's disease.

The degeneration of nigrostriatal dopamine neurons in early Parkinson's disease (PD) is compensated in part by increased transmitter turnover in surviving neurons of the pathway. In this (18)F-dopa positron emission tomography study, we demonstrate compensatory changes in PD in another midbrain dopamine projection to the basal ganglia, the nigropallidal projection to the internal segment of the globus pallidus (GPi). Increased (18)F-dopa uptake in the GPi is seen in early PD which then is lost in advanced PD.

Suprachiasmatic nucleus organization.

The suprachiasmatic nucleus (SCN) of the hypothalamus is a dominant circadian pacemaker in the mammalian brain controlling the rest-activity cycle and a series of physiological and endocrine functions to provide a foundation for the successful elaboration of adaptive sleep and waking behavior. The SCN is anatomically and functionally organized into two subdivisions: (1) a core that lies adjacent to the optic chiasm, comprises predominantly neurons producing vasoactive intestinal polypeptide (VIP) or gastrin-releasing peptide (GRP) colocalized with GABA and receives dense visual and midbrain raphe afferents, and (2) a shell that surrounds the core, contains a large population of arginine vasopressin (AVP)-producing neurons in its dorsomedial portion, and a smaller population of calretinin (CAR)-producing neurons dorsally and laterally, colocalized with GABA, and receives input from non-visual cortical and subcortical regions. In this paper, we present a detailed quantitative analysis of the organization of the SCN core and shell in the rat and place this in the context of the functional significance of the subdivisions in the circadian control of regulatory systems.

Paraventricular-subparaventricular hypothalamic lesions selectively affect circadian function.

The circadian timing system has three principal components: (i) entrainment pathways, (ii) pacemakers, and (iii) efferent pathways from the pacemakers that convey the circadian signal to effector systems. The suprachiasmatic nucleus (SCN) of the hypothalamus is the principal mammalian circadian pacemaker and, although we understand the organization of entrainment pathways to the SCN and the pacemaker itself, we know much less about the functional organization of SCN projections mediating control of effector systems. It is unclear, for example, whether specific subsets of SCN projections control specific effector systems.