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Andreas FRICK




Researcher

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Cursus:
« Dr. rer nat » (PhD): summa cum laude. Institut Max-Planck pour Psychiatrie, Université Technique de Munich, Munich, Allemagne. Superviseur Pr. H. U. Dodt et Pr. H. Zieglgaensberger
Chercheur postdoctorant, boursier d'excellence Feodor Lynen (Alexander von Humboldt foundation). Baylor College of Medicine, Division de Neuroscience, Houston, Texas, Etats-Unis. Superviseur : Pr Daniel Johnston
Chargé de Recherche. Institut Max-Planck pour la Recherche Médicale, Département de Biologie Cellulaire, Heidelberg, Allemagne. Directeur : Pr. Bert Sakmann
Chargé de recherche INSERM «AVENIR », Neurocentre Magendie (2008-2010)
Chercheur INSERM statutaire CR1, Neurocentre Magendie (depuis 2009)






34 publication(s) since Novembre 1998:


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* equal contribution
The indicated IF have been collected by the Web of Sciences in


Abstract:
Dendritic spines are basic units of neuronal information processing and their structure is closely reflected in their function. Defects in synaptic development are common in neurodevelopmental disorders, making detailed knowledge of age-dependent changes in spine morphology essential for understanding disease mechanisms. However, little is known about the functionally important fine-morphological structures, such as spine necks, due to the limited spatial resolution of conventional light microscopy. Using stimulated emission depletion microscopy (STED), we examined spine morphology at the nanoscale during normal development in mice, and tested the hypothesis that it is impaired in a mouse model of fragile X syndrome (FXS). In contrast to common belief, we find that, in normal development, spine heads become smaller, while their necks become wider and shorter, indicating that synapse compartmentalization decreases substantially with age. In the mouse model of FXS, this developmental trajectory is largely intact, with only subtle differences that are dependent on age and brain region. Together, our findings challenge current dogmas of both normal spine development as well as spine dysgenesis in FXS, highlighting the importance of super-resolution imaging approaches for elucidating structure-function relationships of dendritic spines.




11/04/2014 | Brain Struct Funct   IF 4.2
An anterograde rabies virus vector for high-resolution large-scale reconstruction of 3D neuron morphology.
Haberl MG*, Viana da Silva S*, Guest JM, Ginger M, Ghanem A, Mulle C, Oberlaender M, Conzelmann KK, Frick A

Abstract:
Glycoprotein-deleted rabies virus (RABV G) is a powerful tool for the analysis of neural circuits. Here, we demonstrate the utility of an anterograde RABV G variant for novel neuroanatomical approaches involving either bulk or sparse neuronal populations. This technology exploits the unique features of RABV G vectors, namely autonomous, rapid high-level expression of transgenes, and limited cytotoxicity. Our vector permits the unambiguous long-range and fine-scale tracing of the entire axonal arbor of individual neurons throughout the brain. Notably, this level of labeling can be achieved following infection with a single viral particle. The vector is effective over a range of ages (>14 months) aiding the studies of neurodegenerative disorders or aging, and infects numerous cell types in all brain regions tested. Lastly, it can also be readily combined with retrograde RABV G variants. Together with other modern technologies, this tool provides new possibilities for the investigation of the anatomy and physiology of neural circuits.




Abstract:
Dendritic spines are basic units of neuronal information processing and their structure is closely reflected in their function. Defects in synaptic development are common in neurodevelopmental disorders, making detailed knowledge of age-dependent changes in spine morphology essential for understanding disease mechanisms. However, little is known about the functionally important fine- morphological structures, such as spine necks, due to the limited spatial resolution of conventional light microscopy. Using stimulated emission depletion microscopy (STED), we examined spine morphology at the nanoscale during normal development in mice, and tested the hypothesis that it is impaired in a mouse model of fragile X syndrome (FXS). In contrast to common belief, we find that, in normal development, spine heads become smaller, while their necks become wider and shorter, indicating that synapse compartmentalization decreases substantially with age. In the mouse model of FXS, this developmental trajectory is largely intact, with only subtle differences that are dependent on age and brain region. Together, our findings challenge current dogmas of both normal spine development as well as spine dysgenesis in FXS, highlighting the importance of super-resolution imaging approaches for elucidating structure–function relationships of dendritic spines.




2013 | Front Neural Circuits   IF 3.1
Revealing the secrets of neuronal circuits with recombinant rabies virus technology.
Ginger M*, Haberl M*, Conzelmann KK, Schwarz MK, Frick A

Abstract:
An understanding of how the brain processes information requires knowledge of the architecture of its underlying neuronal circuits, as well as insights into the relationship between architecture and physiological function. A range of sophisticated tools is needed to acquire this knowledge, and recombinant rabies virus (RABV) is becoming an increasingly important part of this essential toolbox. RABV has been recognized for years for its properties as a synapse-specific trans-neuronal tracer. A novel genetically modified variant now enables the investigation of specific monosynaptic connections. This technology, in combination with other genetic, physiological, optical, and computational tools, has enormous potential for the visualization of neuronal circuits, and for monitoring and manipulating their activity. Here we will summarize the latest developments in this fast moving field and provide a perspective for the use of this technology for the dissection of neuronal circuit structure and function in the normal and diseased brain.




2013 | Front Neural Circuits   IF 3.1
Three-dimensional tracking and analysis of ion channel signals across dendritic arbors.
Ginger M, Broser P, Frick A

Abstract:
Most neuron types possess elaborate dendritic arbors that receive and integrate excitatory and inhibitory inputs from numerous other neurons to give rise to cell-type specific firing patterns. The computational properties of these dendrites are therefore crucial for neuronal information processing, and are strongly determined by the expression of many types of voltage-gated ion channels in their membrane. The dendritic distribution patterns of these ion channels are characteristic for each ion channel type, are dependent on the neuronal identity, and can be modified in a plastic or pathophysiological manner. We present a method that enables us to semi-automatically map and quantify in 3D the expression levels of specific ion channel types across the entire dendritic arbor. To achieve this, standard immunohistochemistry was combined with reconstruction and quantification procedures for the localization and relative distribution of ion channels with respect to dendritic morphology. This method can, in principle, be applied to any fluorescent signal, including fluorescently tagged membrane proteins, RNAs, or intracellular signaling molecules.




2012 | Nat Commun   IF 12.4
Uncoupling of the endocannabinoid signalling complex in a mouse model of fragile X syndrome.
Jung KM , Sepers M , Henstridge CM , Lassalle O , Neuhofer D , Martin H , Ginger M , Frick A , DiPatrizio NV , Mackie K , Katona I , Piomelli D , Manzoni OJ

Abstract:
Fragile X syndrome, the most commonly known genetic cause of autism, is due to loss of the fragile X mental retardation protein, which regulates signal transduction at metabotropic glutamate receptor-5 in the brain. Fragile X mental retardation protein deletion in mice enhances metabotropic glutamate receptor-5-dependent long-term depression in the hippocampus and cerebellum. Here we show that a distinct type of metabotropic glutamate receptor-5-dependent long-term depression at excitatory synapses of the ventral striatum and prefrontal cortex, which is mediated by the endocannabinoid 2-arachidonoyl-sn-glycerol, is absent in fragile X mental retardation protein-null mice. In these mutants, the macromolecular complex that links metabotropic glutamate receptor-5 to the 2-arachidonoyl-sn-glycerol-producing enzyme, diacylglycerol lipase-alpha (endocannabinoid signalosome), is disrupted and metabotropic glutamate receptor-5-dependent 2-arachidonoyl-sn-glycerol formation is compromised. These changes are accompanied by impaired endocannabinoid-dependent long-term depression. Pharmacological enhancement of 2-arachidonoyl-sn-glycerol signalling normalizes this synaptic defect and corrects behavioural abnormalities in fragile X mental retardation protein-deficient mice. The results identify the endocannabinoid signalosome as a molecular substrate for fragile X syndrome, which might be targeted by therapy.




Abstract:





10/2010 | Cereb Cortex   IF 6.3
Cell type-specific thalamic innervation in a column of rat vibrissal cortex.
Meyer HS, Wimmer VC, Hemberger M, Bruno RM, de Kock CP, Frick A, Sakmann B, Helmstaedter M

Abstract:
This is the concluding article in a series of 3 studies that investigate the anatomical determinants of thalamocortical (TC) input to excitatory neurons in a cortical column of rat primary somatosensory cortex (S1). We used viral synaptophysin-enhanced green fluorescent protein expression in thalamic neurons and reconstructions of biocytin-labeled cortical neurons in TC slices to quantify the number and distribution of boutons from the ventral posterior medial (VPM) and posteromedial (POm) nuclei potentially innervating dendritic arbors of excitatory neurons located in layers (L)2-6 of a cortical column in rat somatosensory cortex. We found that 1) all types of excitatory neurons potentially receive substantial TC input (90-580 boutons per neuron); 2) pyramidal neurons in L3-L6 receive dual TC input from both VPM and POm that is potentially of equal magnitude for thick-tufted L5 pyramidal neurons (ca. 300 boutons each from VPM and POm); 3) L3, L4, and L5 pyramidal neurons have multiple (2-4) subcellular TC innervation domains that match the dendritic compartments of pyramidal cells; and 4) a subtype of thick-tufted L5 pyramidal neurons has an additional VPM innervation domain in L4. The multiple subcellular TC innervation domains of L5 pyramidal neurons may partly explain their specific action potential patterns observed in vivo. We conclude that the substantial potential TC innervation of all excitatory neuron types in a cortical column constitutes an anatomical basis for the initial near-simultaneous representation of a sensory stimulus in different neuron types.




Abstract:





Abstract:
Pyramidal neurons of layer 5A are a major neocortical output type and clearly distinguished from layer 5B pyramidal neurons with respect to morphology, in vivo firing patterns, and connectivity; yet knowledge of their dendritic properties is scant. We used a combination of whole-cell recordings and Ca(2+) imaging techniques in vitro to explore the specific dendritic signaling role of physiological action potential patterns recorded in vivo in layer 5A pyramidal neurons of the whisker-related 'barrel cortex'. Our data provide evidence that the temporal structure of physiological action potential patterns is crucial for an effective invasion of the main apical dendrites up to the major branch point. Both the critical frequency enabling action potential trains to invade efficiently and the dendritic calcium profile changed during postnatal development. In contrast to the main apical dendrite, the more passive properties of the short basal and apical tuft dendrites prevented an efficient back-propagation. Various Ca(2+) channel types contributed to the enhanced calcium signals during high-frequency firing activity, whereas A-type K(+) and BK(Ca) channels strongly suppressed it. Our data support models in which the interaction of synaptic input with action potential output is a function of the timing, rate and pattern of action potentials, and dendritic location.