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Contact

Prof. Dr. Almut Schüz

Address: Spemannstr. 41
72076 Tübingen
Room number: 2.B.12
Phone: +49 7071 601 544
Fax: +49 7071 601 520
E-Mail: almut.schuez

 

Picture of Schüz, Almut, Prof. Dr.

Almut Schüz

Position: Project Leader  Unit: Logothetis

Neuroanatomy and in vivo connectivity

 

Almut Schüz

 

Introduction and Scientific Aims

We investigate the relationship between structure and function, using a variety of anatomical and functional approaches. Four different research programs are pursued at present: a) Functional-anatomical studies on the visual system of marmosets. Marmosets like other New World Monkeys show a genetic dichotomy that affects the expression of photoreceptors sensitive for middle to long (M,L) wavelengths as well as the cellular basis of the parvo stream. As a consequence, most male and some female marmosets are colorblind. However, some females show full trichromatic color vision. This makes the marmoset an important model for investigations on the functional segregation of the visual pathways (color, form and motion). We investigate the arrangement of orientation columns in relation to the location of color domains and thalamic input zones such as CO blobs in V1 and V2 in trichromatic female marmosets and compare the results to those on old world monkeys. b) Anatomical investigations on cortical blood vessels, with the aim to improve the interpretation of hemodynamic signals in functional imaging techniques. c) In vivo tract tracing and histology. The chemists in our institute have developed novel tract tracers for visualizing fibre tracts with magnetic resonance imaging (MRI). In our histological laboratory we compare the MRI-results in rat brains with the postmortem histology of these brains. d) Investigations on fibre thickness in the cortical white matter. The aim of this study is to increase knowledge on conduction times and also to enable us to make better estimates of the number of fibres in fibre bundles within the white matter.

 

Methods

A large variety of techniques is applied in the different projects. a) We use intrinsic optical imaging, microelectrodes and a variety of visual stimuli to map functional domains in the visual system of New World Monkeys. b) The methods to investigate blood vessels are based on fluorescent immunohistochemistry, cytochrome oxidase staining (COX), corrosion cast technique and synchrotron-radiation based X-ray Microscopy (srXTM) with a spatial resolution of 700 nm in a volume of ~1.5 mm³. c) The novel tract tracers for MRI are based on the histological tracer biocytin. Uptake and  transport were investigated in cell cultures (see group by Jörn Engelmann, Dept. High Field MR, Prof. Scheffler) and in histological sections. d) Electron microscopy is used to investigate the thickness of myelinated axons in the white matter of macaques and humans. In particular, we investigate the superior longitudinal fascicle and the uncinate fascicle in both hemispheres, as well as the Corpus callosum.

 

Results and Preliminary Conclusions

     a. Functional-anatomical investigations on the visual system of New World Monkeys.

We developed a histological protocol that facilitates the alignment of functional and anatomical data (also in Magnetic Resonance Imaging studies [1]) and increases accuracy (Fig.1). Thus, errors in alignments are reduced by more than 50% in comparison to those reported in previous studies [2]. We further developed a stimulus protocol that allows us to map color domains by using non-differential optical imaging in trichromatic marmosets. Our results show that color domains are most effectively activated by red-green (L-M) flicker stimuli. We also showed that color domains in marmosets are colocalized with CO blobs in V1 and thin stripes in V2 [3]. We conclude that the observed color domain activation is primarily triggered by a modulation of the parvo stream ((L-M)-cone axis), thus supporting the notion that CO blobs in New World as well as in Old World trichromatic primates are segregated domains of color processing.

 

Figure 1:

Functional-anatomical investigations on the primary visual cortex in marmosets. (A) Orientation map obtained by intrinsic optical imaging (IOI), superimposed onto the 3D reconstruction from the histological sections. (B) Pattern of the superficial cortical vasculature (from the same cortical region) labeled with FITC. Scale bar = 500 µm.

 

    b. Anatomical studies on cortical blood vessels 

Our immunohistochemical approach for visualizing the vascular system resulted in a detailed quantification of vascular densities in layers and areas of the visual cortex [4]. We also could make first estimates of the arterial-venous ratio, derived from corrosion cast preparations (Fig. 2). A tight correlation of vascular density and oxidative metabolism was revealed by immuno­labeling of COX stained sections [5]. The first results of the srXTM approach lead to preliminary 3-dimensional representations of the vasculature, enabling the simulation of changes in cortical blood flow (CBF) [6]. Thus, the methodological portfolio we developed allows for an exact qualitative and quantitative assessment of the cerebral vasculature and can be applied to any brain region of interest.

 

Figure 2:

Scanning electron micrograph of a vascular corrosion cast preparation from the macaque monkey striate cortex. It shows a view across all cortical layers, covering approximately 1.7 mm from surface to white matter, larger arteries and veins shaded red and blue, resp. Automated mosaic-like scanning enables the investigation of large specimens, though with the superior spatial resolution of the scanning electron microscope

 

       c. In vivo tract tracing and histology

As a first step, the histological tracer biocytin was modified in such a way as to make it more stable. The degradation of conventional biocytin starts already a few hours after injection. Higher stability is relevant for MRI studies in which one wants to follow the tracer in vivo over time. Our approach was very successful: using aminopropyl-biocytin or serine-biocytin the stain showed no signs of degradation even 4 days after injection [7]. As a next step, a Gd-complex was coupled to biocytin (Fig. 3) and to both of its new modifications in order to make them visible in MRI. Although in the latter two visualization in histology was impaired (due to an impaired reaction with avidin) it could be shown in MRI that all three molecules were transported to the places to be expected (thalamus; contralateral and ipsilateral cortex) [8, 9].

 

 Figure 3:

Left: Gadolinium complex coupled to biocytin, Ln=Gd3+, Tb3+. Right: MR-pictures and histological pictures after an injection into the motor cortex of the rat. The injection site can be seen as a blue-purple spot on the horizontal MR-picture and as a white spot on the coronal MR-picture, as well as in the histological coronal section beneath it. The red spots in the MR pictures show the location of the tracer after 24 h. The histological picture on the right shows retrogradely stained neurons in the cortex, in the region corresponding to the red spot lateral to the injection site in the coronal MR-picture. From [8].

 

        d. Fibre thickness in the cortical white matter

Fibre thickness in the white matter varies enormously, For example, in the superior longitudinate fascicle. the average of the inner diameter (i.e. without the myelin sheet) is only about 0.7 mm, but can range up to about 5 mm in humans and to about 4 mm in monkeys. Thus, a corresponding range of conduction times is to be expected. This study is gained recently much interest in relation with the development of methods visualizing fibre bundles in vivo (Diffusion Magnetic Resonance Imaging): conventional anatomical data provide an indispensable control for these methods which are not yet well understood and prone to misinterpretation.

 

Supervised students and collaborators

M. F. Valverde Salzmann (PhD thesis on optical imaging in the marmoset)

A. L. Keller (PhD thesis, external supervisor: B. Weber, on blood vessels) 

A. Mishra, R. Mishra, K. Dhingra, J. Engelmann, M. Beyerlein, S. Canals (in vivo tract tracing)

D. Liewald (Diploma thesis on fibre thickness in the white matter)

 

 

References

 

1.         Valverde Salzmann, M.F., N.K. Logothetis, R. Pohmann: High-resolution imaging of vessels in the isolated rat brain. ISMRM: Montreal, Quebec, Canada (2011a).

2.         Valverde Salzmann, M.F., D.J. Wallace, N.K. Logothetis, A. Schüz: Multimodal vessel mapping for precise large area alignment of functional optical imaging data to neuroanatomical preparations in marmosets. Journal of Neuroscience Methods 201, 159-172 (2011b).

3.         Valverde Salzmann, M.F., A. Bartels, N.K. Logothetis, A. Schüz: Color blobs in cortical areas V1 and V2 of the new world monkey Callithrix jacchus, revealed by non-differential optical imaging. Journal of Neuroscience (2011c) (under revision).

4.         Weber B., Keller AL., Reichold J., Logothetis NK. (2008) The microvascular        system of the striate and extrastriate visual cortex of the macaque, Cerebral     Cortex 18 2318-2330.

5.         Keller AL., Schüz A., Logothetis NK., Weber B. (2011) Vascularization of             cytochrome oxidase-rich blobs in the primary visual cortex of squirrel and    macaque monkeys The Journal of Neuroscience 31 1246-1253.

6.         Reichold J., Stampanoni M., Keller AL., Buck A., Jenny P., Weber B (2009)            Vascular graph model to simulate the cerebral blood flow in realistic          vascular networks, Journal of Cerebral Blood Flow & Metabolism 29 1249-      1443.

7.         Mishra A, Dhingra K, Schüz A, Logothetis NK, Canals S (2010) Improved neuronal tract tracing with stable biocytin-derived neuroimaging agents,           ACS Chemical Neuroscience 1 129-138.

8.         Mishra A, Schüz A, Engelmann J, Beyerlein M, Logothetis NK, Canals S (2011)     Biocytin-derived MRI contrast agent for longitudinal brain connectivity     studies  ACS Chem Neurosci Epub ahead DOI: 10.1021/cn200022m.

9.         Mishra A, Dhingra K, Mishra R, Schüz A, Engelmann J, Beyerlein M, Canals S,      Logothetis NK (in press) Biocytin-based contrast agent for molecular

            imaging: an approach to developing new in vivo neuroanatomical tracers   for MRI. In: Neuroimaging / Book 1, (tentative title), Peter Bright  (Ed.), ISBN:      978-953-307-413-9, InTech

 

Education

1976 - 1979 Ph. D. thesis at the Max-Planck-Institute for Biological Cybernetics in Tübingen, on dendritic spines and synapses as a substrate for learning.
1975 Diploma in Biology at the University of Tübingen. (zoology, human physiology, physics, biochemistry).
Diploma thesis at the Max-Planck-Institute for Biological Cybernetics in Tübingen, on dendritic spines in the cerebral cortex.
Supervisor: V. Braitenberg
1969 - 1975 Study of Biology at the University of Tübingen, Germany, and at the Faculty of Sciences, Marseille, France.
1969 Goethe-Gymnasium Ludwigsburg, Abitur

Professional activity

1980 - present Permanent position as a staff scientist at the Max-Planck-Institute for Biological Cybernetics in Tübingen.
Research: Brain Research, by way of quantitative-neuroanatomical methods in connection with brain theory.
Main topic:
Structure and function of the cerebral cortex.
Other topics:
Comparative aspects of the cerebral cortex in various mammals
Variability of the septal area in the human brain
Comparison between neocortex and hippocampus
Plasticity (in neocortex and cerebellum)
Maturation of neurons in organotypic slice-cultures
Winter term 1998/1999 Fellow at the Institute for Advanced Studies in Delmenhorst, Germany;
Projects: 1. outline of an interactive multi-author book on “Cortical Areas: Unity and Diversity”, published in 2002. 2. Co-operation with Prof. Harry Jersion (UCLA) on brain allometry.
1997 - present Conferment of the title "außerplanmäßige Professorin" by the University of Tübingen.
Winter terms 96/97 and 97/98 Teaching of human gross anatomy at the Department of Anatomy in Tübingen (dissection course).
1992 - present “Privat-Dozent” (lectureship) at the Faculty of Biology at the University of Tübingen.
1990 Habilitation in Neurobiology at the University of Tübingen.
1983 and 1991 Guest researcher at the Physiological Institute of the University of St. Petersburg, Russia (at the department of Higher Nervous Activity, Prof. Batuev), cooperation with Dr. G. P. Demianenko.
1982 - present Involved in teaching (neurobiology) at the University of Tübingen.


Organization of international meetings

Jun. 27. 1986 Symposium at the occasion of the 60th birthday of V. Braitenberg, together with A. Aertsen, G. Palm, M. Popp, Tübingen
Jun. 16.-18. 1994 Symposium on "Cell assemblies and Cognition", together with A. Aertsen and G. Palm, Tübingen

Jun. 17.-19. 2006

Symposium on “The legacy of Ramon y Cajal: different kinds of grey matter and their functional significance”, together with N. Logothetis and F. Sultan, Tübingen

Sept. 8.-9. 2011 Workshop on "Synthetic pathways to bio-inspired information processing", together with R. Sigala, Tübingen

  

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Books (5):

Hosp I , Schüz A Person and Braitenberg Z : Tentakel des Geistes: Begegnungen mit Valentin Braitenberg, 324, Edition Raetia, Bolzano, Italy, (2011). ISBN: 978-88-7283-403-9
Schüz A Person and Miller R : Cortical Areas: Unity and Diversity, 526, Taylor & Francis, London, UK, (May-2002). ISBN: 0-415-27723-X
Braitenberg V Person and Schüz A Person: Cortex: Statistics and Geometry of Neuronal Connectivity, 249, Springer, Berlin, Germany, (1998). ISBN: 3-540-63816-4
Braitenberg V Person and Schüz A Person: Anatomy of the cortex: statistics and geometry, 249, Springer, Berlin, Germany, (1991). ISBN: 3-540-53233-1
Aertsen A , Palm G , Popp M and Schüz A Person: Wahrnehmungen des Gehirns: Beiträge zu einem Symposium zum 60. Geburtstag von Valentin Braitenberg, 155, Max-Planck-Institut für Biologische Kybernetik, Tübingen, Germany, (1987).

Articles (30):

Palm G , Knoblauch A , Hauser F and Schüz A Person (March-2014) Cell Assemblies in the Cerebral Cortex Biological Cybernetics . accepted
Sigala R Person, Smerieri A , Schüz A Person, Camorani P and Erokhin V (September-2013) Modeling and simulating the adaptive electrical properties of stochastic polymeric 3D networks Modelling and Simulation in Materials Science and Engineering 21(7) 1-17.
Erokhin V , Berzina T , Gorshkov K , Camorani P , Pucci A , Ricci L , Ruggeri G , Sigala R Person and Schüz A Person (September-2012) Stochastic hybrid 3D matrix: learning and adaptation of electrical properties Journal of Materials Chemistry 22(43) 22881-22887.
Valverde Salzmann MF Person, Bartels A Person, Logothetis NK Person and Schüz A Person (June-2012) Color Blobs in Cortical Areas V1 and V2 of the New World Monkey Callithrix jacchus, Revealed by Non-Differential Optical Imaging Journal of Neuroscience 32(23) 7881-7894.
Schüz A Person (November-2011) Valentin Braitenberg: Nachruf Nervenheilkunde 2011(11) 930-931.
pdf
Mishra A Person, Schüz A Person, Engelmann J Person, Beyerlein M Person, Logothetis NK Person and Canals S Person (October-2011) Biocytin-derived MRI contrast agent for longitudinal brain connectivity studies ACS Chemical Neuroscience 2(10) 578–587.
Valverde Salzmann MF Person, Wallace DJ Person, Logothetis NK Person and Schüz A Person (September-2011) Multimodal vessel mapping for precise large area alignment of functional optical imaging data to neuroanatomical preparations in marmosets Journal of Neuroscience Methods 201(1) 159-172.
Keller AL Person, Schüz A Person, Logothetis NK Person and Weber B Person (January-2011) Vascularization of Cytochrome Oxidase-Rich Blobs in the Primary Visual Cortex of Squirrel and Macaque Monkeys Journal of Neuroscience 31(4) 1246-1253.
Voges N , Schüz A Person, Aertsen A and Rotter S (November-2010) A modeler's view on the spatial structure of intrinsic horizontal connectivity in the neocortex Progress in Neurobiology 92(3) 277-292.
Mishra A Person, Dhingra K Person, Schüz A Person, Logothetis NK Person and Canals S Person (February-2010) Improved neuronal tract-tracing with stable biocytin-derived neuroimaging agents ACS Chemical Neuroscience 1(2) 129-138.
Erokhin V , Schüz A Person and Fontana MP (January-2010) Organic Memristor and Bio-Inspired Information Processing International Journal of Unconventional Computing 6(1) 15-32.
Schüz A Person (February-2008) Neuroanatomy Scholarpedia 3(3) 3158.
Schüz A Person, Chaimow D Person, Liewald D Person and Dortenmann M Person (October-2006) Quantitative Aspects of Corticocortical Connections: A Tracer Study in the Mouse Cerebral Cortex 16(10) 1474-1486.
Smirnakis SM Person, Schmid MC Person, Brewer AA , Tolias AS Person, Schüz A Person, Augath MA Person, Inhoffen W , Wandell BA and Logothetis NK Person (November-2005) Neuroscience: Rewiring the adult brain (Reply) Nature 438(7065) E3-E4.
Smirnakis SM Person, Brewer AA , Schmid MC Person, Tolias AS Person, Schüz A Person, Augath M Person, Inhoffen W , Wandell BA and Logothetis NK Person (May-2005) Lack of long-term cortical reorganization after macaque retinal lesions Nature 435(7040) 300-307.
Schüz A Person and Preissl H (October-1996) Basic connectivity of the cerebral cortex and some considerations on the corpus callosum. Neuroscience and Biobehavioral Reviews 20(4) 567-570.
Schüz A Person and Demianenko GP (January-1995) Constancy and variability in cortical structure. A study on synapses and dendritic spines in hedgehog and monkey Journal of Brain Research 36(1) 113-122.
pdf
Schüz A Person (September-1994) Patchiness as a means to get a message across Trends in Neurosciences 17(9) 365-365.
Hellwig B , Schüz A Person and Aertsen A (May-1994) Synapses on axon collaterals of pyramidal cells are spaced at random intervals: A Golgi study in the mouse cerebral cortex Biological Cybernetics 71(1) 1-12.
Caeser M and Schüz A Person (July-1992) Maturation of neurons in neocortical slice cultures. A light and electron microscopic study on in situ and in vitro material Journal für Hirnforschung 33(4-5) 429-443.
Schüz A Person and Palm G (August-1989) Density of neurons and synapses in the cerebral cortex of the mouse Journal of Comparative Neurology 286(4) 442-455.
Braitenberg V Person and Schüz A Person (May-1989) Cortex: hohe Ordnung oder grösstmögliches Durcheinander? Spektrum der Wissenschaft 1989(5) 74-86.
Schüz A Person and Dortenmann M (November-1987) Synaptic density on non-spiny dendrites in the cerebral cortex of the house mouse. A phosphotungstic acid study Journal für Hirnforschung 28(6) 633-639.
Schüz A Person (February-1986) Comparison between the dimensions of dendritic spines in the cerebral cortex of newborn and adult Guinea pigs Journal of Comparative Neurology 244(3) 277-285.
Krone G , Mallot HA Person, Palm G and Schüz A Person (January-1986) Spatiotemporal receptive fields: A dynamical model derived from cortical architectonics Proceedings of the Royal Society of London B 226(1245) 421-444.
Koch F , Schüz A Person and Kariks J (July-1985) Comparison of the septal areas in New Guinean and European brains American Journal of Physical Anthropology 67(3) 259-267.
Schüz A Person and Münster A (May-1985) Synaptic density on the axonal tree of a pyramidal cell in the cortex of the mouse Neuroscience 15(1) 33-39.
Schüz A Person (January-1981) Pränatale Reifung und postnatale Veränderung im Cortex des Meerschweichens: Mikroskopische Auswertung eines natürlichen Deprivationsexperimentes. II. Postnatale Veränderungen Journal für Hirnforschung 22(1) 113-127.
Schüz A Person (January-1981) Pränatale Reifung und postnatale Veränderung im Cortex des Meerschweinchens: Mikroskopische Auswertung eines natürlichen Deprivationsexperimentes. I. Pränatale Reifung Journal für Hirnforschung 22(1) 93-111.
Schüz A Person (May-1976) Pyramidal cells with different densities of dendritic spines in the cortex of the mouse Zeitschrift für Naturforschung C 31(5-6) 319-323.

Conference papers (7):

Aertsen A , Erb M , Palm G and Schüz A Person (1994) Coherent assembly dynamics in the cerebral cortex: multi-unit recordings, network simulations and anatomical considerations In: Oscillatory event related brain dynamics, NATO Advanced Research Workshop on Oscillatory Event Related Brain Dynamics 1993, Plenum Press, New York, NY, USA, 59-83.
Schüz A Person and Braitenberg V Person (1994) Constraints to a random plan of cortical connectivity In: Structural and Functional Organization of the Neocortex, Symposium in the Memory of Otto D. Creutzfeldt 1993, Springer, Berlin, Germany, 161-169.
Braitenberg V Person and Schüz A Person (1992) Basic features of cortical connectivity and some considerations on language In: Language Origin: a Multidisciplinary Approach, NATO Advanced Study Institute on Language Origin: a Multidisciplinary Approach 1988, Kluwer, Dordrecht, Netherlands, 89-102.
Schweizer M and Schüz A Person (June-1990) What comes first: the dendritic spine or its synapse? An electron microscopical investigation In: Brain - Perception - Cognition, 18th Göttingen Neurobiology Conference, Thieme, Stuttgart, Germany, 37.
Schüz A Person (1988) Some conclusions, relevant to plasticity, derived from normal anatomy In: Cellular mechanisms of conditioning and behavioral plasticity, Symposium on the "Cellular mechanisms of conditioning and behavioral plasticity", Plenum Press, New York, NY, USA, 265-272.
Schüz A Person (1987) Die Feinstruktur der Großhirnrinde oder: wie paßt das Gehirn in den Kopf? In: Wahrnehmungen des Gehirns, Symposion zum 60. Geburtstag von Valentin Braitenberg 1986, Max-Planck-Institut für Biologische Kybernetik, Tübingen, Germany, 17-38.
Schüz A Person (1981) Prenatal formation of synapses and dendritic spines in Guinea-pig cortex and their postnatal changes In: Advances in physiological sciences 30: Neural communication and control, 28th International Congress of Physiological Sciences 1980, Oxford, UK, Pergamon Press, 279-285.

Contributions to books (16):

Mishra A Person, Mishra R Person, Canals S Person, Logothetis NK Person, Beyerlein M Person, Engelmann J Person, Schüz A Person and Dhingra K Person: Biocytin-based contrast agents for molecular imaging: an approach to developing new in vivo neuroanatomical tracers for MRI, 181-204. In: Neuroimaging - Methods, (Ed) P. Bright, InTech, Rijeka, Croatia, (February-2012).
Schüz A Person: Die Macht der Fasern: Hirnforschung von und mit Valentin Braitenberg, 90-101. In: Tentakel des Geistes: Begegnungen mit Valentin Braitenberg, (Ed) I. Hosp, Edition Raetia, Bolzano, Italy, (2011).
Schüz A Person and Sultan F : Brain Connectivity and Brain Size, 317-326. In: Encyclopedia of Neuroscience, (Ed) L. R. Squire, Academic Elsevier, London, UK, (January-2009).
Schüz A Person: Neuroanatomy in a Computational Perspective, 733-736. In: The Handbook of Brain Theory and Neural Networks, (Ed) M.A. Arbib, MIT Press, Cambridge, MA, USA, (2003).
Miller R and Schüz A Person: Discussion Section, 459-495. In: Cortical areas: unity and diversity, (Ed) A. Schüz, Taylor & Francis, London, UK, (May-2002).
Schüz A Person: Homogeneity and Heterogeneity of Cortical Structure: A Theme and its Variations, 1-11. In: Cortical areas: unity and diversity, (Ed) A. Schüz, Taylor & Francis, London, UK, (May-2002).
Schüz A Person and Braitenberg V Person: The Human Cortical White Matter: Quantitative Aspects of Cortico-Cortical Long-Range Connectivity, 377-385. In: Cortical areas: unity and diversity, (Ed) A. Schüz, Taylor & Francis, London, UK, (May-2002).
Schüz A Person: What can the cerebral cortex do better than other parts of the brain?, 491-500. In: Brain evolution and cognition, (Ed) G. Roth, Wiley, New York, NY, USA, (January-2001).
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