Showing papers by "Ann M. Graybiel published in 1987"

Neuronal loss in the pedunculopontine tegmental nucleus in Parkinson disease and in progressive supranuclear palsy

Abstract: In the brains of humans and other mammals, there are two principal groups of cholinergic nuclei aside from those forming the cranial motor nuclei. One group lies in the forebrain and includes the nucleus basalis of Meynert. The second group lies in the hindbrain and includes the nucleus tegmenti pedunculopontinus (NPP), identified by Mesulam et al. [Mesulam, M.-M., Mufson, E. J., Wainer, B. H. & Levey, A. I. (1983) Neuroscience 10, 1185-1201] as cholinergic cell group Ch5. The basal forebrain cholinergic cell groups, which innervate widespread areas of the neocortex, undergo degeneration in Alzheimer disease and also in parkinsonism associated with dementia. We here report that the hindbrain NPP Ch5 cell group, thought to innervate many nuclei of the extrapyramidal motor system, the superior colliculus, and the substantia innominata, undergoes degeneration in idiopathic Parkinson disease and in the parkinsonian syndrome of progressive supranuclear palsy. These findings strongly suggest that degeneration in the brainstem in Parkinson disease is not confined to catecholamine-containing neurons, but that cholinergic neurons of the NPP are also vulnerable. The findings further raise the possibility that certain symptoms of Parkinson disease and progressive supranuclear palsy have their genesis in pathology of these cholinergic neurons.

Differences in tyrosine hydroxylase-like immunoreactivity characterize the mesostriatal innervation of striosomes and extrastriosomal matrix at maturity.

Abstract: Tyrosine hydroxylase [TyrOHase, tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (2-hydroxylating), EC 1.14.16.2] is the rate-limiting enzyme in the synthetic pathway of catecholamines and is expressed by neurons containing dopamine, norepinephrine, and epinephrine. TyrOHase is present in high concentrations in the caudate nucleus and putamen, where nearly all of it is contained in axons of the dopaminergic mesostriatal pathways. We have employed three different polyclonal antibodies directed against TyrOHase, one tested here for specificity by two-dimensional gel electrophoresis, to reexamine the anatomic distribution of fibers expressing TyrOHase-like immunoreactivity in the striatum of mature human, monkey, and cat brains. The findings suggest that this distribution is distinctly inhomogeneous. The macroscopic compartments known as striosomes have low TyrOHase-like immunoreactivity relative to the surrounding extrastriosomal matrix. These observations add to evidence that dopaminergic modulation of neural processing in the mature striatum is organized in accordance with striosomal architecture and suggest that part of the mechanism for such differentiation may involve presynaptic differences in enzymatic regulation of dopamine content in and out of striosomes.

Ectosylvian visual area of the cat: location, retinotopic organization, and connections.

Abstract: We have mapped out the ectosylvian visual area (EVA) of the cat in a series of single- and multiunit recording studies. EVA occupies 10-20 mm2 of cortex at the posterior end of the horizontal limb of the anterior ectosylvian sulcus. EVA borders on somatosensory cortex anteriorly, auditory cortex posteriorly, and nonresponsive cortex laterally. EVA exhibits limited retinotopic organization, as indicated by the fact that receptive fields shift gradually with tangential travel of the microelectrode through cortex. However, a point-to-point representation of the complete visual hemifield is not present. We have characterized the afferent and efferent connections of EVA by placing retrograde and anterograde tracer deposits in EVA and in other cortical visual areas. The strongest transcortical fiber projection to EVA arises in the lateral suprasylvian visual areas. Area 20, the granular insula, and perirhinal cortex provide additional sparse afferents. The projection from lateral suprasylvian cortex to EVA arises predominantly in layer 3 and terminates in layer 4. EVA projects reciprocally to all cortical areas from which it receives input. The projection from EVA to the lateral suprasylvian areas arises predominantly in layers 5 and 6 and terminates in layer 1. EVA is linked reciprocally to a thalamic zone encompassing the lateromedial-suprageniculate complex and the adjacent medial subdivision of the latero-posterior nucleus. We conclude that EVA is an exclusively visual area confined to the anterior ectosylvian sulcus and bounded by nonvisual cortex. EVA is distinguished from other visual areas by its physical isolation from those areas, by its lack of consistent global retinotopic organization, and by its placement at the end of a chain of areas through which information flows outward from the primary visual cortex.

The postnatal development of the dopamine-containing innervation of dorsal and ventral striatum: effects of the weaver gene

Abstract: We report here that the pattern of loss of dopamine that occurs in the brains of adult mice carrying the autosomal recessive weaver gene is the consequence both of failed postnatal development of the dopamine- containing mesostriatal innervation and of the disappearance of the early forming dopamine-island system For these studies, we compared the contents of dopamine extracted from 3 divisions of the striatum, the caudoputamen, nucleus accumbens, and olfactory tubercle, and from the midbrain of weaver and control littermate pups Catecholamines were extracted from tissues dissected from serial brain slices and were separated and measured using high-performance liquid chromatography followed by electrochemical detection The anatomical pattern formed by the catecholamine-containing innervation of the developing striatum was studied in 8-, 11-, 20-d-old, and 15-month-old weaver and control mice using tyrosine hydroxylase immunohistochemistry In weaver neonates (7- 8 d old), the dopamine-containing innervation of the caudoputamen is characterized by near-normal concentrations of dopamine and by a normal anatomical arrangement of dopamine islands Subsequently, however, the weaver disease is expressed in the caudoputamen as a failure of the dopamine islands to persist and of the dopamine-containing innervation of the matrix to develop at a normal rate Whereas the concentration of dopamine increases 44-fold between days 7 and 33 in normal animals, it increases only 16-fold in the weaver In spite of the severe reduction of dopamine, the weaver9s caudoputamen grows to near-normal size (85%)(ABSTRACT TRUNCATED AT 250 WORDS)

Weaver--a mutant gene that affects the basal ganglia

Abstract: Soon after evidence for a mesotelencephalic dopamine-containing pathway finally became unassailable, the dual nature of this projection was recognized (Anden et al. 1966; Ungerstedt, 1971). The two divisions of the path described by these investigators are: (1) the nigrostriatal system, which originates mainly in the dopamine-containing neurons of the substantia nigra’s pars compacta (cell group A9 of Dahlstrom and Fuxe, 1964) and innervates most of the caudoputamen, and (2) the mesolimbic system, which originates mainly in the dopamine-containing cells of the ventral tegmental area (cell groups A10 of Dahlstrom and Fuxe, 1964) and innervates the nucleus accumbens, most of the olfactory tubercle and the ventral part of the caudoputamen (Ungerstedt, 1971; Bjorklund and Lindvall, 1984; Fallon and Moore, 1978; Beckstead et al., 1979). The nigrostriatal and mesolimbic pathways are also separable on the basis of their other neural affiliations. The nigrostriatal system with its target the dorsal caudoputamen are associated with sensorimotor systems whereas the mesolimbic system and the ventral striatum are associated with limbic regions, a relationship clearly embedded in the name given to this pathway (Kelley et al., 1982; Heimer and Wilson, 1975; Graybiel and Ragsdale, 1979).