Douglas M. Bowden

Catecholamine systems as the neural substrate for intracranial self-stimulation: a hypothesis.

Abstract The hypothesis was investigated that activation of central catecholamine (CA) systems is essential for intracranial self-stimulation (ICSS). Brain sites that support ICSS in the rat were found to be highly correlated with electrodes in 3 major CA systems: the mesolimbic and nigrostriatal dopaminergic systems and the dorsal noradrenergic system. Stimulation at ICSS loci in the brain stem causes release of catecholamines at terminals in ascending CA systems. Lesion studies show suppression of ICSS proportional to the degree of damage to the stimulated CA system. Drugs influence ICSS in accordance with their effects on transmission at dopaminergic and noradrenergic synapses. Enhancement of nicotinic-cholinergic mechanisms facilitates ICSS, but the effect requires that CA mechanisms be intact. Neurophysiological experiments suggest that two systems characterized by different axonal refractory periods are involved in ICSS. The data are insufficient to determine whether these correspond to the dopamine and norepinephrine systems. Norepinephrine has an inhibitory effect at many postsynaptic receptor sites, and ICSS is often accompanied by reduction or cessation of cellular discharges in NE terminal areas. Food ingestion has also been demonstrated to produce an inhibitory effect on cells in a noradrenergic terminal area. ICSS has been demonstrated in numerous species, including man, in brain areas that overlap considerably with loci whose stimulation supports ICSS in the rat. Stimulation of ICSS loci in man is commonly associated with verbal reports of intense pleasurable sensations.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian syndrome in Macaca fascicularis: which midbrain dopaminergic neurons are lost?

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces, in both human and non-human primates, a syndrome very similar to idiopathic Parkinsons disease. The syndrome is associated with degeneration of the dopamine-containing neurons in the substantia nigra, many of which project to the neostriatum. The purpose of the present study was to quantify the regional distribution of midbrain dopamine neurons remaining after MPTP administration to the monkey (Macaca fascicularis) and to develop alternative procedures for maintaining the normal nutrition in MPTP-treated animals. Three monkeys were treated with MPTP and three served as controls. Representative sections were examined from rostral to caudal through the midbrain dopamine cell nuclei and the location of every tyrosine hydroxylase-containing cell was entered into a computer. Midbrain dopamine neuronal cell loss ranged from 36-78%, being most extensive in the two monkeys which exhibited the most severe parkinsonian syndrome. The greatest cell loss (46-93%) occurred in the substantia nigra pars compacta, or nucleus A9, and the loss was primarily in the ventral portion of the nucleus. Contrary to most previous reports, however, there was also a loss of cells in the ventral tegmental area (28-57%) and ventral reticular formation (33-87%), corresponding to nuclei A10 and A8, respectively. Since neuroanatomical tracing studies have shown that the dorsal and lateral portions of the striatum (areas showing the greatest dopamine depletion after MPTP) receive input from cells in the ventral A9 and from cells in the A8 and A10 areas, the present data suggest that MPTP preferentially destroys dopamine cells that project to the striatum (i.e. the mesostriatal cells).

Primate neostriatal neurons containing tyrosine hydroxylase: Immunohistochemical evidence

We have detected, in monkey caudate nucleus and putamen, neuronal cell bodies containing tyrosine hydroxylase-like immunoreactivity, as revealed by peroxidase-antiperoxidase immunohistochemistry. Many of these cells are distributed in an outer rim of 1-2 mm throughout the anterior-posterior extent of the neostriatum near its borders with the corona radiata; others are embedded in the adjacent white matter, especially near the ventral putamen and nucleus accumbens. Light and electron microscopy indicate that they are small (8-12 micron), bipolar cells with large nuclei. Such neostriatal neurons, containing tyrosine hydroxylase-like immunoreactivity, number in the tens of thousands.

The Neuroscience Information Framework: A Data and Knowledge Environment for Neuroscience

With support from the Institutes and Centers forming the NIH Blueprint for Neuroscience Research, we have designed and implemented a new initiative for integrating access to and use of Web-based neuroscience resources: the Neuroscience Information Framework. The Framework arises from the expressed need of the neuroscience community for neuroinformatic tools and resources to aid scientific inquiry, builds upon prior development of neuroinformatics by the Human Brain Project and others, and directly derives from the Society for Neuroscience’s Neuroscience Database Gateway. Partnered with the Society, its Neuroinformatics Committee, and volunteer consultant-collaborators, our multi-site consortium has developed: (1) a comprehensive, dynamic, inventory of Web-accessible neuroscience resources, (2) an extended and integrated terminology describing resources and contents, and (3) a framework accepting and aiding concept-based queries. Evolving instantiations of the Framework may be viewed at http://nif.nih.gov, http://neurogateway.org, and other sites as they come on line.

NeuroNames Brain Hierarchy.

The NeuroNames Brain Hierarchy is a structured system of neuroanatomical terminology that provides a comprehensive representation of virtually all human and nonhuman primate brain structures that are identifiable either grossly or in Niss1-stained histological sections. This system was devised for computer applications to address deficiencies in the brain terminology presented in Nomina Anatomica. English terms are listed for 783 structures in nine levels of hierarchical ranking. Abbreviations are provided for all superficial and primary volumetric structures. The substructures that constitute the total volume of every superstructure are identified. Superficial features of the brain are clearly distinguished from internal, volumetric brain structures. Structures found solely in either humans or macaques are identified. The purpose of the NeuroNames Brain Hierarchy is to bring greater standardization to the neuroanatomical terminology used by scientific investigators, clinicians, and students. This effort is consistent with the goals of the Unified Medical Language System program of the National Library of Medicine. It is hoped that the systematic construction of the NeuroNames Brain Hierarchy will facilitate use of the most widely accepted definitions of classical neuroanatomy in quantitative computerized neuroimaging applications. It should provide an accurate structural framework against which to reference the many other kinds of neuroanatomical information that are acquired by modern imaging, mapping, and histological labeling techniques.

A stereotaxic template atlas of the macaque brain for digital imaging and quantitative neuroanatomy.

A stereotaxic brain atlas of the longtailed macaque (Macaca fascicularis) is presented in a format suitable for use as a template atlas of the macaque brain. It includes most of the brain segmented to show the boundaries of landmark structures such that every point in the brain can be represented by a unique set of coordinates in three-dimensional space and ascribed unambiguously to one and only one primary structure. More than 400 structures are represented, including 360 volumetric structures, which constitute the substance of the brain, and 50 superficial features. To facilitate use with ventriculography, magnetic resonance imaging, and other noninvasive imaging techniques, the stereotaxic space is referenced to internal landmarks, viz., the anterior commissure and posterior commissure; the center of the anterior commissure at the midline is the origin of the stereotaxic axes. Reference of stereotaxis to this bicommissural space facilitates structural comparison with human brain atlases, which are commonly referenced to the biocommissural line. It also facilitates comparison of brains of different nonhuman primate species by providing a template brain against which to compare size and internal variability. Thirty-three coronal sections at 1-mm intervals from the spinomedullary junction to the rostral extreme of the caudate nucleus show most structures of the hindbrain, midbrain, and subcortical forebrain. Separately, four side views and 16 coronal sections show cortical structures. Structures are represented by outlines of their boundaries and labeled according to NeuroNames, a systematic English nomenclature of human and nonhuman primate neuroanatomy. Abbreviations are based on a protocol designed to facilitate cross-species comparisons. Instructions are provided for: (1) locating sites from the Template Atlas in the conventional stereotaxic space of an experimental animal, (2) locating sites identified by conventional stereotaxis in the Template Atlas, and (3) using the Template Atlas to collate, compare, and display image information (e.g., labeled cells, recording sites, stimulation sites, lesions) from multiple animals.

Fetal alcohol syndrome: A new primate model for binge drinking and its relevance to human ethanol teratogenesis

Ethanol was administered nasogastrically to four gravid pigtailed macaques (Macaca nemestrina) weekly from 40 days after conception to term. Three animals received 2.5 gm/kg and one received 4.1 gm/kg per dose. One animal aborted after the first dose of 2.5 gm/kg ethanol. Serum ethanol and acetaldehyde were measured after each dose in the other three animals, who carried to term. After delivery the infants were assessed for growth, dysmorphic features, and neurologic and psychological development over six months and were compared with 10 age- and sex-matched controls. Complete autopsies with neuropathologic examinations were performed. The animal exposed to the high dose had neurologic, developmental, and facial anomalies similar to those seen in human fetal alcohol syndrome. One of the animals exposed to the more moderate dosage was similarly but less severely affected. The study demonstrates that a model for binge drinking and fetal alcohol syndrome can be developed in a primate. The model should be useful in exploring the mechanisms of teratogenesis and in determining the median effective dose for the production of the various anomalies seen in fetal alcohol syndrome.

An autoradiographic, semistereotaxic mapping of major projections from locus coeruleus and adjacent nuclei in Macaca mulatta

The autoradiographic method was used to trace projections from the monkey locus coeruleus (LC) and adjacent nuclei (nn. parabrachiales, n. tractus mesencephalicus nervus trigemini, substantia grisea centralis). Pathways attributed to LC are presented diagrammatically in a set of 26 coronal sections. They include a descending pathway along the tractus tegmentalis centralis, a caudal pathway entering the corpus medullaris cerebellaris via the lateral wall and roof of ventriculus quartus, and an ascending pathway along the tractus tegmentalis centralis giving off branches to the commissura posterior, tractus habenulo-interpeduncularis, centrum medianum and n. ventralis posteromedialis thalami, fasciculus lenticularis, lamina medullaris thalami lateralis, capsula interna, commissura supraoptica dorsalis, tractus supraoptico-hypophyseus, stria terminalis, laminae medullaris interna and medialis and pars interna of globus pallidus, corpus subfornicale, capsula externa, stria longitudinalis, cingulum, and gyrus rectus. A contribution to the branches entering n. ventralis posteromedialis thalami and the commissura supraoptica dorsalis was attributed to the nn. parabrachiaels. Axons entering trigeminal structures via the tractus mesencephalicus nervus trigemini were attributed to labeling of cells in the nucleus of that tract. Terminal areas attributed to labeling of LC axons were evident in decreasing order of density in the bed nucleus of stria terminalis, substantia innominata, nn. amygdalae anterior, centralis and basalis (dorsal portion), nn. paraventricularis, supraopticus and dorsomedialis hypothalami, and n. antero-ventralis thalami.

Behavior, Appetite, and Urinary Cortisol Responses by Adult Female Pigtailed Macaques to Cage Size, Cage Level, Room Change, and Ketamine Sedation

Pigtailed macaques (Macaca nemestrina) and longtailed macaques (M. fascicularis) show behavioral, ecological, and possible temperament differences, and their responses to the laboratory environment might therefore be quite different. We tested pigtailed macaques under the same conditions that were investigated in a previous study with longtailed macaques, using the same comprehensive set of physiological and behavioral measures of stress. First, eight adult females’ adaptation to a new room in regulation‐size cages was monitored, and in the third week their responses to ketamine sedation were measured. Then they spent two weeks singly housed in each of four cage sizes (USDA regulation size, one size larger, one size smaller, and a very small cage). Half of the subjects were in upper‐level cages and the remainder in lower‐level cages for the entire study. Cage size, ranging from 20% to 148% of USDA regulation floor area, was not significantly related to abnormal behavior, self‐grooming, manipulating the environment, eating/drinking, activity cycle, cortisol excretion, or biscuit consumption. Locomotion and frequency of behavior change were significantly reduced in the smallest cage, but did not differ in cage sizes ranging from 77% to 148% of regulation size. The only manipulation to produce an unequivocal stress response, as measured by cortisol elevation and appetite suppression, was ketamine sedation. Room change and cage changes were associated with minimal cortisol elevation and appetite suppression. Wild‐born females showed more appetite suppression after room change than captive‐born females. No differences were related to cage level. Pigtailed macaques strongly resembled longtailed macaques except they showed weaker responses to the new room and cage change, probably because the pigtails had spent more time in captivity. These findings support the conclusion that increasing cage size to the next regulation size category would not have measurable positive effects on the psychological well‐being of two species of laboratory macaques. Am. J. Primatol. 52:63–80, 2000.

The INIA19 Template and NeuroMaps Atlas for Primate Brain Image Parcellation and Spatial Normalization

The INIA19 is a new, high-quality template for imaging-based studies of non-human primate brains, created from high-resolution, T1-weighted magnetic resonance (MR) images of 19 rhesus macaque (Macaca mulatta) animals. Combined with the comprehensive cortical and sub-cortical label map of the NeuroMaps atlas, the INIA19 is equally suitable for studies requiring both spatial normalization and atlas label propagation. Population-averaged template images are provided for both the brain and the whole head, to allow alignment of the atlas with both skull-stripped and unstripped data, and thus to facilitate its use for skull stripping of new images. This article describes the construction of the template using freely available software tools, as well as the template itself, which is being made available to the scientific community (http://nitrc.org/projects/inia19/).