Name:
Geert M.J. Ramakers
Department Neuroscience and Pharmacology
Section Neurobiology of Behaviour
Function:
Assistant Professor
E-mail:
g.m.j.ramakers@umcutrecht.nl Tel: +31 88 7568413
Mobile:+31-650487918
Research group:
Frank Meye – Graduate Student
Edwin Alserda – Graduate Student
Ischa Bruinsma – Master Student
Eljo van Battum – Master Student
Bernat Gonzales-Llinares – Master Student
Title research line:
Cellular and synaptic plasticity
Summary research:
I am interested in cellular and synaptic plasticity. I want to know how neurons integrate synaptic signals and convert these signals into output signals (action potentials). Research focusses on two brain areas: the hippocampus and the midbrain dopamine system (ventral tegmental area and striatum). Whole cell patch-clamp and field potential recordings in vitro are primarily used to study these phenomena.
Aims:
Plasticity of neural circuits plays an important role during development, learning and ongoing behaviour. Plasticity of neural systems can result from alterations in synaptic strength, as well as changes in neuronal excitability. Unraveling the mechanisms underlying plasticity is fundamental in understanding the physiology of learning and memory and pathophysiology of neurological diseases (e.g. addiction). The aim of our research is to delineate specific processes involved in synaptic and cellular plasticity and eventually the role of these processes in physiological and pathophysiological conditions.
Experimental strategy and key results:
Our experimental strategy is to identify how specific signal transduction cascades (G-protein coupled receptors, axon guidance molecules) or behavioral activity influence activity-dependent synaptic and cellular plasticity using in vitro electrophysiological and pharmacological approaches. These studies are carried out in close collaboration with other members of the section Neurobiology of Behavior and the section Neurodevelopment. Part of the work is funded by the TI Pharma initiative.
Student Projects:
• G-protein coupled receptors and synaptic integration in the ventral tegmental area
Aim: determine how GPCRs regulate excitatory and inhibitory input to dopamine neurons in the VTA.
Experimental work: whole-cell patch clamp recordings, pharmacology, immunohistochemistry.
• The role of axon guidance molecules in acticity-dependent synaptic plasticity in the hippocampus
Aim: determine if and how axon guidance molecules regulate LTP and LTD in the CA1 field of the hippocampus.
Experimental work: field potential recordings, pharmacology.
• The role of G-protein coupled receptors in cellular and synaptic plasticity in the striatum
Aim: determine how GPCRs regulate cellular excitability and excitatory and inhibitory input to medium spiny neurons in the striatum.
Experimental work: whole-cell patch clamp recordings, pharmacology, immunohistochemistry.
• Measuring dopamine overflow in the striatum using fast scan cyclic voltammetry
Aim: quantify stimulus-induced dopamine overflow in the striatum and determine the effect of repeated drug exposure on stimulus-induced dopamine overflow.
Experimental work: fast scan cyclic voltammetry, pharmacology.
Publications:
1: De Rover M, Meye, FM, Ramakers GM. Presynaptic metabotropic glutamate receptors regulate glutamatergic input to dopamine neurons in the ventral tegmental area. Neuroscience (2008) http://dx.doi.org/10.1016/j.neuroscience.2008.04.055
2: Kramer ER, Aron L, Ramakers GM, Seitz S, Zhuang X, Beyer K, Smidt MP, Klein R. Absence of Ret signaling in mice causes progressive and late degeneration of the nigrostriatal system. PLoS Biol. (2007), 5(3):e39..
3: Sgadò P, Albéri L, Gherbassi D, Galasso SL, Ramakers GM, Alavian KN, Smidt MP, Dyck RH, Simon HH. Slow progressive degeneration of nigral dopaminergic neurons in postnatal Engrailed mutant mice. Proc Natl Acad Sci U S A. (2006), 103(41):15242-7.
4: van der Heide LP, Ramakers GM, Smidt MP. Insulin signaling in the central nervous system: learning to survive. Prog Neurobiol. (2006), 79(4):205-21.
5: Mathon DS, Vanderschuren LJ, Ramakers GM. Reduced psychostimulant effects on dopamine dynamics in the nucleus accumbens of mu-opioid receptor knockout mice. Neuroscience (2006), 141(4):1679-84.