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Andreas FRICK

Principal Investigator

Phone : 33(0)5 57 57 37 04
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« 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)

37 publication(s) since Novembre 1998:

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

02/2004 | Nat Neurosci   IF 20.1
LTP is accompanied by an enhanced local excitability of pyramidal neuron dendrites.
Frick A, Magee J, Johnston D

The propagation and integration of signals in the dendrites of pyramidal neurons is regulated, in part, by the distribution and biophysical properties of voltage-gated ion channels. It is thus possible that any modification of these channels in a specific part of the dendritic tree might locally alter these signaling processes. Using dendritic and somatic whole-cell recordings, combined with calcium imaging in rat hippocampal slices, we found that the induction of long-term potentiation (LTP) was accompanied by a local increase in dendritic excitability that was dependent on the activation of NMDA receptors. These changes favored the back-propagation of action potentials into this dendritic region with a subsequent boost in the Ca(2+) influx. Dendritic cell-attached patch recordings revealed a hyperpolarized shift in the inactivation curve of transient, A-type K(+) currents that can account for the enhanced excitability. These results suggest an important mechanism associated with LTP for shaping signal processing and controlling dendritic function.

10/2003 | J Neurophysiol   IF 2.2
A modified Sindbis vector for prolonged gene expression in neurons.
Jeromin A, Yuan LL, Frick A, Pfaffinger P, Johnston D

Sindbis viruses have been widely used in neurobiology to express a variety of genes in cultured neurons, in cultured slices, and in vivo. They provide fast onset and high levels of expression of foreign genes, but the expression is limited to a short time window due to a shut-off of host protein synthesis. We have used a mutation in an essential gene (nsP2) of the life cycle of Sindbis, which allows the functional analysis of changes in protein expression for >/=6 days after infection. This Sindbis mutant (nsP2) was used to express enhanced green fluorescent protein (EGFP) in hippocampal neurons in culture and in vivo without any sign of toxicity, based on two-photon imaging and electrophysiology. In addition, the EGFP mutant virus can be injected in vivo to visualize spines and other details of neuronal structure. The Sindbis mutant described here provides an improved tool in neurobiology with reduced cytotoxicity and a prolonged time window of expression for novel applications in imaging and behavior. In addition, the use of this vector for the functional expression of mammalian voltage-gated ion channels in organotypic slices is demonstrated.

29/04/2003 | Philos Trans R Soc Lond B Biol Sci   IF 5.7
Active dendrites, potassium channels and synaptic plasticity.
Johnston D, Christie BR, Frick A, Gray R, Hoffman DA, Schexnayder LK, Watanabe S, Yuan LL

The dendrites of CA1 pyramidal neurons in the hippocampus express numerous types of voltage-gated ion channel, but the distributions or densities of many of these channels are very non-uniform. Sodium channels in the dendrites are responsible for action potential (AP) propagation from the axon into the dendrites (back-propagation); calcium channels are responsible for local changes in dendritic calcium concentrations following back-propagating APs and synaptic potentials; and potassium channels help regulate overall dendritic excitability. Several lines of evidence are presented here to suggest that back-propagating APs, when coincident with excitatory synaptic input, can lead to the induction of either long-term depression (LTD) or long-term potentiation (LTP). The induction of LTD or LTP is correlated with the magnitude of the rise in intracellular calcium. When brief bursts of synaptic potentials are paired with postsynaptic APs in a theta-burst pairing paradigm, the induction of LTP is dependent on the invasion of the AP into the dendritic tree. The amplitude of the AP in the dendrites is dependent, in part, on the activity of a transient, A-type potassium channel that is expressed at high density in the dendrites and correlates with the induction of the LTP. Furthermore, during the expression phase of the LTP, there are local changes in dendritic excitability that may result from modulation of the functioning of this transient potassium channel. The results support the view that the active properties of dendrites play important roles in synaptic integration and synaptic plasticity of these neurons.

15/04/2003 | J Neurosci   IF 5.7
Normalization of Ca2+ signals by small oblique dendrites of CA1 pyramidal neurons.
Frick A, Magee J, Koester HJ, Migliore M, Johnston D

Oblique dendrites of CA1 pyramidal neurons predominate in stratum radiatum and receive approximately 80% of the synaptic input from Schaffer collaterals. Despite this fact, most of our understanding of dendritic signal processing in these neurons comes from studies of the main apical dendrite. Using a combination of Ca2+ imaging and whole-cell recording techniques in rat hippocampal slices, we found that the properties of the oblique dendrites differ markedly from those of the main dendrites. These different properties tend to equalize the Ca2+ rise from single action potentials as they backpropagate into the oblique dendrites from the main trunk. Evidence suggests that this normalization of Ca2+ signals results from a higher density of a transient, A-type K+ current [I(K(A))] in the oblique versus the main dendrites. The higher density of I(K(A)) may have important implications for our understanding of synaptic integration and plasticity in these structures.

09/2001 | J Neurophysiol   IF 2.2
Glutamate receptors form hot spots on apical dendrites of neocortical pyramidal neurons.
Frick A, Zieglgansberger W, Dodt HU

Apical dendrites of layer V cortical pyramidal neurons are a major target for glutamatergic synaptic inputs from cortical and subcortical brain regions. Because innervation from these regions is somewhat laminar along the dendrites, knowing the distribution of glutamate receptors on the apical dendrites is of prime importance for understanding the function of neural circuits in the neocortex. To examine this issue, we used infrared-guided laser stimulation combined with whole cell recordings to quantify the spatial distribution of glutamate receptors along the apical dendrites of layer V pyramidal neurons. Focally applied (<10 microm) flash photolysis of caged glutamate on the soma and along the apical dendrite revealed a highly nonuniform distribution of glutamate responsivity. Up to four membrane areas (extent 22 microm) of enhanced glutamate responsivity (hot spots) were detected on the dendrites with the amplitude and integral of glutamate-evoked responses at hot spots being three times larger than responses evoked at neighboring sites. We found no association of these physiological hot spots with dendritic branch points. It appeared that the larger responses evoked at hot spots resulted from an increase in activation of both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors and not a recruitment of voltage-activated sodium or calcium conductances. Stimulation of hot spots did, however, facilitate the triggering of both Na+ spikes and Ca(2+) spikes, suggesting that hot spots may serve as dendritic initiation zones for regenerative spikes.

01/10/1999 | Science   IF 41.8
Precisely localized LTD in the neocortex revealed by infrared-guided laser stimulation.
Dodt H, Eder M, Frick A, Zieglgansberger W

In a direct approach to elucidate the origin of long-term depression (LTD), glutamate was applied onto dendrites of neurons in rat neocortical slices. An infrared-guided laser stimulation was used to release glutamate from caged glutamate in the focal spot of an ultraviolet laser. A burst of light flashes caused an LTD-like depression of glutamate receptor responses, which was highly confined to the region of 'tetanic' stimulation (<10 micrometers). A similar depression of glutamate receptor responses was observed during LTD of synaptic transmission. A spatially highly specific postsynaptic mechanism can account for the LTD induced by glutamate release.

11/1998 | Eur J Neurosci   IF 3.1
NMDA and AMPA receptors on neocortical neurons are differentially distributed.
Dodt HU, Frick A, Kampe K, Zieglgansberger W

The distribution of glutamate receptor subtypes on the surface of neurons is highly relevant for synaptic activation and signal processing in the neocortex. As a novel approach we have used infra-red videomicroscopy in combination with photostimulation or microiontophoresis in brain slices of rat neocortex to map the distribution of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on pyramidal neurons of layer V. Both modes of application revealed a spatially distinct distribution of glutamate receptor subtypes: the soma and the proximal dendrite of neurons are highly sensitive to NMDA, whereas the more distal parts of the dendrite are more sensitive to AMPA. An implication is that NMDA receptors near the soma might regulate the amplification of synaptic signals resulting from AMPA receptor activation on remote dendritic sites.