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Worthy, K. H.

Publications and source records attributed to Worthy, K. H..

7 recordsLinked to original sources

Giant pyramidal neurons of the primary motor cortex express vasoactive intestinal polypeptide (VIP), a known marker of cortical interneurons

Vasoactive intestinal polypeptide (VIP) is known to be present in a subclass of cortical interneurons that are involved in the disinhibition of excitatory pyramidal neurons. Here, using three different antibodies, we demonstrate that VIP is also present in the giant layer 5 pyramidal (Betz) neurons which are characteristic of the limb and axial representations of the marmoset primary motor cortex (cytoarchitectural area 4ab). No VIP staining was observed in smaller layer 5 pyramidal cells present in the primary motor facial representation (cytoarchitectural area 4c), or in premotor cortex (e.g. the caudal subdivision of the dorsal premotor cortex, A6DC), indicating the selective expression of VIP in Betz cells. The most intense VIP staining occurred in the largest Betz cells, located in the medial part of A4ab. VIP in Betz cells was colocalized with neuronal specific marker (NeuN) and a calcium-binding protein parvalbumin (PV). PV also intensely labelled axon terminals surrounding Betz cell somata. Whereas Betz cells bodies were located in layer 5, VIP-positive (VIP+) interneurons were more abundant in the superficial cortical layers. They constituted about 5-7% of total cortical neuronal population, with the highest density observed in area 4c. Our results demonstrate the expression of VIP in the largest excitatory neurons of the primate cortex, which may offer new functional insights into the role of VIP in the brain, and also provide opportunities for genetic manipulation of Betz cells.

neuroscience↗

Distribution of calbindin-positive neurons across areas and layers of the marmoset cerebral cortex

The calcium-binding protein calbindin is selectively expressed in specific neuronal populations of the cerebral cortex, including major classes of inhibitory interneurons. We have charted the distribution of calbindin-positive (CB+) neurons across areas and layers of the entire marmoset cortex using a combination of immunohistochemistry, AI-based image segmentation, 3-dimensional reconstruction, and cytoarchitecture-aware registration. CB+ neurons formed 10-20% of the cortical neuronal population, occurring in higher proportions in areas corresponding to low hierarchical levels of processing, such as sensory cortices. Although CB+ neurons concentrated in the supragranular layers, there were clear trends in laminar distribution: the relative density in infragranular layers increased with hierarchical level, and the density in layer 4 was lowest in areas involved in sensorimotor integration and action planning. These results reveal new aspects of the cytoarchitectural organization of the primate cortex and demonstrate an efficient approach to mapping the full distribution of neurochemically distinct cell types throughout the brain, readily applicable to most mammalian species and parts of the nervous system.

neuroscience↗

Rapid degeneration and neurochemical plasticity of the lateral geniculate nucleus following lesions of the primary visual cortex in marmoset monkeys

Lesions of the primary visual cortex (V1) cause retrograde neuronal degeneration, volume loss and neurochemical changes in the lateral geniculate nucleus (LGN). Here we characterise the timing of these processes, by comparing the LGN of adult marmoset monkeys following various recovery times after unilateral V1 lesions. Observations in NeuN-stained sections obtained from animals with very short (3 days) recoveries showed that the volume and neuronal density in the LGN ipsilateral to the lesions were similar to those in the contralateral hemispheres. However, neuronal density in the LGN lesion projection zones (LPZ) dropped rapidly thereafter, with a loss of [~]50% of the population occurring within a month of the lesions. This level of neuronal loss was then sustained for the remainder of the range of recovery times, up to >3 years post-lesion. In comparison, shrinkage of the LGN progressed more gradually, not reaching a stable value until 6 months post lesion. We also determined the time course of the expression of the calcium-binding protein calbindin (CB) in magnocellular (M) and parvocellular (P) layer neurons, a recently described form of neurochemical plasticity triggered by V1 lesions. We found that CB expression could be detected in surviving M and P neurons as early as 1 month after a lesion, with the percentage of neurons showing this neurochemical phenotype showing subtle changes over 6 months. Our study shows that there is a limited time window for any possible interventions aimed at reducing secondary neuronal loss in the visual afferent pathways following damage to V1.

neuroscience↗

Afferent connections of cytoarchitectural area 6M and surrounding cortex in the marmoset: putative homologues of the supplementary and pre-supplementary motor areas

Cortical projections to the caudomedial frontal cortex were studied using retrograde tracers in marmosets. We tested the hypothesis that cytoarchitectural area 6M includes homologues of the supplementary and pre-supplementary motor areas (SMA and preSMA) of other primates. We found that, irrespective of the injection sites location within 6M, over half of the labeled neurons were located in motor and premotor areas. Other connections originated in prefrontal area 8b, ventral anterior and posterior cingulate areas, somatosensory areas (3a and 1-2), and areas on the rostral aspect of the dorsal posterior parietal cortex. Although the origin of afferents was similar, injections in rostral 6M received higher percentages of prefrontal afferents, and fewer somatosensory afferents, compared to caudal injections, compatible with differentiation into SMA and preSMA. Injections rostral to 6M (area 8b) revealed a very different set of connections, with increased emphasis in prefrontal and posterior cingulate afferents, and fewer parietal afferents. The connections of 6M were also quantitatively different from those of M1, dorsal premotor areas, and cingulate motor area 24d. These results show that the cortical motor control circuit is conserved in simian primates, indicating that marmosets can be valuable models for studying movement planning and control.

neuroscience↗

Histology-Based Average Template of the Marmoset Cortex With Probabilistic Localization of Cytoarchitectural Areas

The rapid adoption of marmosets in neuroscience has created a demand for three dimensional (3D) atlases of the brain of this species to facilitate data integration in a common reference space. We report on a new open access template of the marmoset cortex (the Nencki-Monash, or NM template), representing a morphological average of 20 brains of young adult individuals, obtained by 3D reconstructions generated from Nissl-stained serial sections. The method used to generate the template takes into account morphological features of the individual brains, as well as the borders of clearly defined cytoarchitectural areas. This has resulted in a resource which allows direct estimates of the most likely coordinates of each cortical area, as well as quantification of the margins of error involved in assigning voxels to areas, and preserves quantitative information about the laminar structure of the cortex. We provide spatial transformations between the NM and other available marmoset brain templates, thus enabling integration with magnetic resonance imaging (MRI) and tracer-based connectivity data. The NM template combines some of the main advantages of histology-based atlases (e.g. information about the cytoarchitectural structure) with features more commonly associated with MRI-based templates (isotropic nature of the dataset, and probabilistic analyses). The underlying workflow may be found useful in the future development of brain atlases that incorporate information about the variability of areas in species for which it may be impractical to ensure homogeneity of the sample in terms of age, sex and genetic background. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/036632v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@11d61f6org.highwire.dtl.DTLVardef@a9156org.highwire.dtl.DTLVardef@1cbdc84org.highwire.dtl.DTLVardef@fa738c_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIA 3D template of the marmoset cortex representing the average of 20 individuals. C_LIO_LIThe template is based on Nissl stain and preserves information about cortical layers. C_LIO_LIProbabilistic mapping of areas, cortical thickness, and layer intensity profiles. C_LIO_LIIncludes spatial transformations to other marmoset brain atlases. C_LI AbbreviationsFor a list of areas and their abbreviations see Table S2.

neuroscience↗

Neuronal distribution across the cerebral cortex of the marmoset monkey (Callithrix jacchus)

Using stereological analysis of NeuN-stained sections, we investigated neuronal density and number of neurons per column throughout the marmoset cortex. Estimates of mean neuronal density encompassed a greater than threefold range, from >150,000 neurons/ mm3 in the primary visual cortex to ~50,000 neurons/ mm3 in the piriform complex. There was a trend for density to decrease from posterior to anterior cortex, but also local gradients, which resulted in a complex pattern; for example, in frontal, auditory and somatosensory cortex neuronal density tended to increase towards anterior areas. Anterior cingulate, motor, premotor, insular and ventral temporal areas were characterized by relatively low neuronal densities. Analysis across the depth of the cortex revealed greater laminar variation of neuronal density in occipital, parietal and inferior temporal areas, in comparison with other regions. Moreover, differences between areas were more pronounced in the supragranular layers than in infragranular layers. Calculations of the number of neurons per unit column revealed a pattern that was distinct from that of neuronal density, including local peaks in the posterior parietal, superior temporal, precuneate, frontopolar and temporopolar regions. These results suggest that neuronal distribution in adult cortex result from a complex interaction of developmental/ evolutionary determinants and functional requirements.

neuroscience↗

Unidirectional monosynaptic connections from auditory areas to the primary visual cortex in the marmoset monkey

Until the late 20th Century, it was believed that different sensory modalities were processed by largely independent pathways in the primate cortex, with cross-modal integration only occurring in specialized polysensory areas. This model was challenged by the finding that the peripheral representation of the primary visual cortex (V1) receives monosynaptic connections from areas of the auditory cortex in the macaque. However, auditory projections to V1 have not been reported in other primates. We investigated the existence of direct interconnections between V1 and auditory areas in the marmoset, a New World monkey. Labelled neurons in auditory cortex were observed following 4 out of 10 retrograde tracer injections involving V1. These projections to V1 originated in the caudal subdivisions of auditory cortex (primary auditory cortex, caudal belt and parabelt areas), and targeted parts of V1 that represent parafoveal and peripheral vision. Injections near the representation of the vertical meridian of the visual field labelled few or no cells in auditory cortex. We also placed 8 retrograde tracer injections involving core, belt and parabelt auditory areas, none of which revealed direct projections from V1. These results confirm the existence of a direct, nonreciprocal projection from auditory areas to V1 in a different primate species, which has evolved separately from the macaque for over 30 million years. The essential similarity of these observations between marmoset and macaque indicate that early-stage audiovisual integration is a shared characteristic of primate sensory processing.

neuroscience↗