Search Results - (Author, Cooperation:R. Apps)

2013-09-14

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

*Gene Expression Regulation ; HIV/*immunology ; HIV Infections/*genetics/*immunology ; HLA-C Antigens/*genetics ; Humans ; T-Lymphocytes, Cytotoxic/*immunology

2013-04-06

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

African Americans/genetics ; Alleles ; Amino Acid Sequence ; Anti-Retroviral Agents/therapeutic use ; Crohn Disease/genetics/immunology ; *Gene Expression Regulation ; HIV/genetics/*immunology ; HIV Infections/drug therapy/*genetics/*immunology ; HLA-C Antigens/*genetics ; Humans ; Immunodominant Epitopes/genetics ; Molecular Sequence Data ; Mutation ; Peptide Fragments/immunology ; Polymorphism, Single Nucleotide ; T-Lymphocytes, Cytotoxic/*immunology ; Viral Load/genetics

1460-9568

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The inferior olive climbing fibre projection is key to cerebellar contributions to motor control. Here we present evidence for a novel tool, trans-crotononitrile (TCN), to selectively inactivate the olive to study its functions. Anatomical, electrophysiological and behavioural techniques have been used in rats to assess the CNS effects of TCN, with a focus on the olivocerebellar projection. These findings were compared with those obtained with 3-acetylpyridine (plus nicotinamide administered 3.5 h later, 3AP + 3.5 h). Fluoro-Jade B cell labelling showed that TCN and 3AP + 3.5 h induce neurodegeneration primarily within the inferior olive, with no other targets in common. Recordings of evoked field potentials on the cerebellar cortical surface showed that both neurotoxins can reduce transmission in climbing fibre but not mossy fibre pathways. Both histological and electrophysiological differences suggest that TCN and 3AP have distinct mechanisms of action. Estimates of the numbers of surviving cells within individual subdivisions of the olive indicate that TCN and 3AP + 3.5 h cause different patterns of subtotal olivary lesion: most surviving neurons are present in the rostral (TCN) or caudal (3AP + 3.5 h) parts of the medial accessory olive, which are associated with two different cerebellar modules: the C2 and A modules, respectively. In behavioural studies, TCN and 3AP + 3.5 h produced differences in motor deficits consistent with the notion that these cerebellar modules have distinct functional responsibilities. Thus, studies using TCN as compared with 3AP + 3.5 h have the potential to shed light on the contributions of different cerebellar modules in motor control.

Electronic Resource

1460-9568

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The paravermal cerebellar cortex contains three spatially separate zones (the C1, C3 and Y zones) which form a functionally coupled system involved in the control of voluntary limb movements. A series of ‘modules’ has been postulated, each defined by a set of olivary neurons with similar receptive fields, the cortical microzones innervated by these neurons and the group of deep cerebellar nuclear neurons upon which the microzones converge. A key feature of this modular organization is a correspondence between cortical input and output, irrespective of the zonal identity of the microzone. This was tested directly using a combined electrophysiological and bi-directional tracer technique in barbiturate-anaesthetized cats. During an initial operation, small injections of a mix of retrograde and anterograde tracer material (red beads combined with Fluoro-Ruby or green beads combined with biotinylated dextran amine or Fluoro-Emerald) were made into areas of the medial C1 and medial C3 zones in cerebellar lobule V characterized by olivo-cerebellar input from the ventral forelimb. The inferior olive and the deep cerebellar nuclei were then scrutinized for retrogradely labelled cells and anterogradely labelled axon terminals, respectively. For individual experiments, the degree of C1–C3 zone terminal field overlap in the nucleus interpositus anterior was plotted as a function of either the regional overlap of single-labelled cells or the proportion of double-labelled cells in the dorsal accessory olive. The results were highly positively correlated, indicating that cortico-nuclear convergence between parts of the two zones is in close proportion to the corresponding olivo-cerebellar divergence, entirely consistent with the modular hypothesis.

Electronic Resource

1460-9568

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The olivocerebellar and corticonuclear connections of the forelimb area of the paravermal medial C3 zone were studied in the cat using a combined electrophysiological and fluorescent tracer technique. During an initial operation under barbiturate anaesthesia, lobules IV/V of the cerebellar anterior lobe were exposed and small injections of dextran amines tagged with rhodamine or fluorescein were made into areas selected from four different electrophysiologically defined parts of the zone. The inferior olive and the deep cerebellar nuclei were then scrutinized for retrogradely labelled cells and anterogradely labelled axon terminals respectively. The findings demonstrate a detailed topographical organization within the olivocerebellar projection to the medial C3 zone and provide some evidence for a topographical organization of its projection to nucleus interpositus anterior. Both projections are described at a level of resolution not previously attained in neuroanatomical studies and the results strongly support the notion of a micro-compartmentalization of cerebellar olivo-corticonuclear circuits.

Electronic Resource

1476-4687

Nature Archives 1869 - 2009

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

[Auszug] During April and May 1972, and again from September to December 1972, we used the 10 cm 650 kW Plessey 43S weather radar of the Royal Observatory, Hong Kong, to detect and study the northward spring and southward autumn migrations of birds over the south coast of China, and particularly over areas ...

Electronic Resource

1432-1106

Inferior olive ; Cerebellum ; Climbing fibres ; Cerebellar zones ; Cat

Springer Online Journal Archives 1860-2000

Medicine

Summary The olivocerebellar projection to the c1,c2 and c3 zones in the paravermal cortex of lobule Vb/c has been investigated in the cat using a combined electrophysiological/neuroanatomical tracing technique. The zonal boundaries in the paravermal cortex were located by recording, on the cerebellar surface, climbing fibre field potentials evoked in response to percutaneous stimulation of one or more paws. A small (10–30 nl) injection of WGA-HRP was then made either into the centre or into the medial or lateral geographical half of a chosen zone and the resultant distribution of retrogradely labelled cells within the contralateral inferior olive was plotted. The c1 and c3 zones were each found to consist of two mediolaterally oriented ‘sub-zones’ which could be distinguished by their olivocerebellar input. The medial part of the c1 zone received climbing fibre input from the rostromedial part of the dorsal accessory olive (DAO) while the lateral part of the c1 zone received climbing fibre input from middle/rostral regions of the medial accessory olive (MAO). Both medial and lateral ‘sub-zones’ within the c3 zone were found to receive climbing fibre input from the rostral pole of DAO but, whereas there was heavy overlap between the olivary territories projecting to the medial c1 and medial c3 subzones, olivary cells projecting to the lateral part of c3 were located more rostrally within DAO. The c2 zone was found not to be divisible into mediolaterally oriented subzones and to receive climbing fibre input from a region of MAO located rostral and somewhat lateral to the region projecting to the lateral part of the c1 zone. The sub-zonal organisation of the olivocerebellar projection to the c1, c2 and c3 zones is discussed in relation to the functional properties of the different zones.

Electronic Resource

1432-1106

Nucleocortical ; Corticonuclear ; Cerebellar nuclei ; Cerebellar zonation ; Cat

Springer Online Journal Archives 1860-2000

Medicine

Summary The projection from the intracerebellar nuclei to the paravermal (intermediate) cerebellar cortex of lobule Vb/c has been investigated in the cat using a combined electrophysiological and neuroanatomical technique. A small (10–30 nl) injection of WGA-HRP was made into one of the three paravermal zones (c1, c2 or c3) after the mediolateral boundaries of the zones had been delimited on the cerebellar surface by recording climbing fibre field potentials evoked in response to percutaneous stimulation of one or more paws. The distribution of retrogradely labelled cell bodies within the intracerebellar nuclei was compared with the distribution of terminal labelling arising from anterograde transport by cerebellar Purkinje cells. The three paravermal zones displayed marked heterogeneity in their receipt of a projection from the intracerebellar nuclei. The c1 and c3 zones received virtually no such input, although injections in either zone resulted in significant terminal labelling (which was largely restricted to nucleus interpositus anterior). By contrast, the intervening c2 zone received a much heavier nucleocortical input which arose almost exclusively from nucleus interpositus posterior (to which the zone also projected). A sparse contralateral nucleocortical input to the c2 zone was also demonstrated. This arose primarily from nucleus fastigius. It is concluded that the nucleocortical projection to the paravermal cortex of lobule Vb/c displays marked topographical specificity and some functional implications of this are discussed.

Electronic Resource

1432-1106

Inferior olive ; Cerebellum ; Climbing fibres ; Branching ; Fluorescent tracers

Springer Online Journal Archives 1860-2000

Medicine

Summary The pattern of transverse branching in the olivocerebellar projection to the x zone in the vermis and the lateral c1 zone in the paravermis of the cat anterior lobe was studied using a combined electrophysiological and retrograde double-labelling tracer technique. Fluorochrome-tagged latex microspheres were well suited for this purpose. The results show that the region of olive that supplies climbing fibres to the two zones forms a continuous, rostrocaudally directed column about 2.25 mm in length, in a caudo-lateral to rostromedial part of the medial accessory olive (MAO), on average between A-P levels 12.50-10.50. This column may be divided into caudal and rostral halves that project respectively to the x and lateral c1 zones in the apical folia of lobules V/VIa. Partial overlap between these two territories occurs in an intermediate region (A-P levels 12.00-11.00) in middle MAO where olive cells that supply climbing fibres to either x or lateral c1 are intermingled with a smaller population of cells whose axons branch to provide climbing fibres to both zones. Quantitative analysis showed that, when different tracers were injected into each zone in the same animal, double-labelled cells represented only 5–7% of either single-labelled cell population within this area of overlap. It is concluded that, although some transverse branching is present within the olivocerebellar projection to the x and lateral c1 zones in the apical folia of lobule V, such branching is not extensive.

Electronic Resource

1432-1106

Key words Purkinje cells ; Cerebellar nuclei ; Cerebellar zonation

Springer Online Journal Archives 1860-2000

Medicine

Abstract  The cortico-nuclear (C–N) and nucleo-cortical (N–C) projections of the C1 cortical zone in pars anterior (pa) and pars copularis (pc) of the paramedian lobule (PML) in the posterior lobe of the cat cerebellum were investigated with a combined electrophysiological and neuroanatomical technique. In each experiment the medio-lateral boundaries of the zone were located on the cortical surface by recording field potentials mediated via climbing fibres and evoked in the zone by activity elicited in spino-olivocerebellar paths through percutaneous stimulation of fore- and hindlimbs; a small (15–30 nl) injection of WGA-HRP was then made into the zone. The distributions in the deep cerebellar nuclei were determined (with light microscopy) both for terminal labelling due to anterograde axonal transport by Purkinje cells and for cell bodies labelled due to retrograde transport in N–C axons. The extent to which injection sites were confined to the C1 zone was assessed both by comparing injection site and zone widths and by determining the distributions of retrogradely labelled neurones within the contralateral inferior olive. The C–N projection from the part of the zone in PML pa (a forelimb part) terminates almost exclusively (perhaps exclusively) in nucleus interpositus anterior (NIA), primarily in caudal and dorsal parts, where it overlaps heavily with the C–N projections from the lobule V parts (also forelimb parts) of the C1 and C3 zones as previously defined. The C–N projection from the part of the zone in PML pc (a hindlimb part) also terminates virtually exclusively in NIA but primarily in almost all parts of the medial third of the nucleus. There is, nevertheless, sufficient overlap between the PML pa and PML pc projections that approximately one third of the termination territory of each projection overlaps that of the other. The PML pc part of the zone is almost entirely lacking in a N–C projection, as previously found for the lobule V part of the C1 zone (and C3 zone). However, the PML pa part of the zone receives N–C projections that arise, in descending order of size, from nucleus interpositus posterior (NIP), from NIA, from the NIA/nucleus lateralis (NL) fusion area and (perhaps) NL. The projection from NIP is similar in size to that provided by the nucleus to the C2 zone in lobule V of the anterior lobe. The findings are discussed, with particular emphasis on their implications for the hypothesis that the cerebellum is divisible into a number of olivo-cortico-nuclear complexes or compartments.

Electronic Resource

1432-1106

Key words Purkinje cells ; Cerebellar nuclei ; Cerebellar zonation

Springer Online Journal Archives 1860-2000

Medicine

Abstract  The cortico-nuclear (C-N) and nucleo-cortical (N-C) projections of the C2 cortical zone in pars anterior (pa) and pars posterior (pp) of the paramedian lobule (PML) in the posterior lobe of the cat cerebellum were investigated with a combined electrophysiological and neuroanatomical technique. In each experiment the medio-lateral boundaries of the zone were localized on the cortical surface by recording field potentials mediated via climbing fibres and evoked in the zone by activity elicited in spino-olivocerebellar paths through percutaneous stimulation of the fore- and hindlimbs; a small (15–30 nl) injection of 1–2% WGA-HRP was then made into the zone. Distributions in the deep cerebellar nuclei were determined with light microscopy both for C-N terminal labelling due to anterograde axonal transport by Purkinje cells and for cell bodies labelled due to retrograde transport in N-C axons. The extent to which retrogradely labelled olivary neurones were confined to the part of the rostral medial accessory olive that innervates the C2 zone was estimated to provide an indication of the degree to which the injected tracer might have spread beyond the boundaries of the zone. The C-N projection from the part of the C2 zone in PML pa terminates almost exclusively (probably exclusively) in nucleus interpositus posterior (NIP) at all medio-lateral levels of the nucleus but most extensively at middle and lateral levels. At most levels the C-N termination territory forms a crescent with its outer curve following the caudal, dorsal and rostral borders of the nucleus and as a result it is mainly in the dorsal half of the nucleus. There is heavy overlap with the projection from the lobule V part of the C2 zone previously studied by us. The projection from the C2 zone in PML pp terminates entirely in NIP, but although at middle medio-lateral levels in the nucleus there is substantial overlap with the PML pa and lobule V projections, the projection territory is confined to the medial half of the nucleus. Evidence was obtained compatible with the view that throughout the C2 zone its lateral and medial parts project to different parts of NIP. In both PML pa and pp the C2 zone receives N-C projections from NIP. Most of the N-C cells concerned are in the dorsal half of NIP and the great majority lie within the corresponding C-N projection territory. However, the N-C projection to PML pa appears c. 6 times heavier than that to PML pp and the PML pa part of the zone also receives a minor additional projection from nucleus lateralis (NL). The findings are discussed in relation to the hypothesis of olivo-cortico-nuclear complexes or compartments, with particular reference to the internal organization of the C2 complex.

Electronic Resource