Neuroanatomy & in vivo Connectivity

We use various neuroanatomical methods (quantitative hodology, in vivo tract tracing with MR contrast agents, allometry, and 3D-structural analysis) and combinations of neuroanatomical and functional methods (tract tracing combined with fMRI, or histology combined with optical imaging and electrophysiology) to examine the intricate connectivity of the brain, the correlation between histology and neuronal activity in the visual cortex, and the fine 3D organization of cortical microvasculature.

Brain Connectivity

A: The density of fibers can be quantified by counting the number of intersections with lines projected onto a terminal field. B: Representative coronal plot of neurons retrogradely labeled with differently labeled tract tracers injected at distinct locations within the insula of a macaque monkey. C: High-resolution T1-weighted anatomical scan (MDEFT) showing an injection site (light spot) of modified biocytin conjugated with gadolinium in the somatosensory cortex of a rat.

Neuroanatomy reveals the network structure within and between brain regions. Knowing the network structure is a fundamental prerequisite for understanding mechanisms behind brain functions. We investigate connectivity using four different approaches:

  1. Quantitative connectivity in the cerebral cortex. This is a study on the cortico-cortical connectivity in the mouse [1] based on the anterograde tracer biotinylated dextran amine (Figure 1A). The study quantifies the rich connectivity of the cortex within itself and allows the development of a generalized model of horizontal connectivity in the cortex [2].

  2. Anatomofunctional connectivity in the insular cortex in the macaque monkey. We combine high-resolution tract tracing (Figure 1B) with our department's advanced MRI and fMRI to examine the neuronal connections of the insular cortex in the macaque monkey. This examination contributes to our understanding of how the insula integrates bodily sensations with emotions – and how it might engender a sense of self awareness in humans. 2) Anatomofunctional connectivity in the insular cortex in the macaque monkey. We combine high-resolution tract tracing (Figure 1B) with our department's advanced MRI and fMRI to examine the neuronal connections of the insular cortex in the macaque monkey. This examination contributes to our understanding of how the insula integrates bodily sensations with emotions – and how it might engender a sense of self awareness in humans.

  3. In vivo connectivity using new contrast agents. Our chemists develop tracers (modified biocytin) which can be detected by magnetic resonance imaging (MRI) and which have some advantages over the previously used manganese [3,4]. Histological investigations in combination with MRI studies (Figure 1C) are in progress in order to see if the modified tracers are taken up and transported as efficiently as conventional biocytin. 3) In vivo connectivity using new contrast agents. Our chemists develop tracers (modified biocytin) which can be detected by magnetic resonance imaging (MRI) and which have some advantages over the previously used manganese [3,4]. Histological investigations in combination with MRI studies (Figure 1C) are in progress in order to see if the modified tracers are taken up and transported as efficiently as conventional biocytin.

  4. Allometric study of the cerebral and the cerebellar cortex.The size of the cerebral and the cerebellar cortex increases indifferent ways with global brain size in different mammalian species. This phenomenon can be explained by the different network structure within the cerebral and cerebellar cortex.

Orientation Selectivity in V1

Illustration of the combination of theory, physiology and anatomy (from top to bottom) applied in our project on V1. Cytochrome oxidase blobs (bottom) have a similar distance as the assumed orientation centers (top).

This study combines intrinsic optical imaging, electrophysiology and cytochrome oxidase staining (Figure 2). The aim of this study is to test predictions of a theory on the mechanism behind orientation selectivity [5], in particular, the prediction that cytochrome oxidase blobs are centered in hypercolumns within which each orientation is represented twice.

Cortical Blood Vessels

Scanning electron micrographs of vascular corrosion cast preparations from the macaque monkey striate cortex, with a view across all cortical layers. Larger arteries and veins shaded red and blue.

This qualitative and quantitative study examines the distribution of blood vessels and their 3D structural characteristics in various cortical areas (Figure 3). This study is highly relevant for the interpretation of fMRI studies.

Literature

  1. Schüz A., D. Chaimow, D. Liewald, M. Dortenmann: Quantitative Aspects of Corticocortical Connections: A Tracer Study in the Mouse. Cerebral Cortex 16, 1474–1486 (2006).
  2. Voges, N., A. Schüz, A. Aertsen, S. Rotter: A Modeler‘s View on the Spatial Structure of Intrinsic Horizontal Connectivity in the Neocortex. Progress in Neurobiology, (submitted) (2010).
  3. Saleem, K. S., J. Pauls, M. A. Augath, T. Trinath, B. A. Prause, T. Hashikawa, N. K. Logothetis: Magnetic Resonance Imaging of Neuronal Connections in the Macaque Monkey. Neuron 34, 685–700 (2002).
  4. Canals, S., M. Beyerlein, A. L. Keller, Y. Murayama, N. K. Logothetis: Magnetic Resonance Imaging of Cortical Connectivity in vivo. Neuroimage 40(2), 458–472 (2008).
  5. Braitenberg V.: Charting the Visual Cortex. In Cerebral Cortex, Vol. 3, 379–414. (Eds.) Peters A., Jones E. G. Plenum, New York, USA (1985).
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