Research: Synaptic plasticity: cellular mechanisms, development of functional networks and links to behaviour My lab's interest lies in activity-dependent synaptic plasticity with respect to its relevance for learning and memory as well as the underlying physiological and molecular mechanisms. In order to bridge the gap from changes in cellular connectivity to behavioral consequences, and furthermore, to get a better grip on the molecular mechanisms involved, I decided to shift my attention from the brain slices in rat to the zebrafish, the obvious advantage being that this is one of the most promising models for forward genetic screens, thus connecting mutations on the molecular level with behavioral or morphological defects. The aim of my work will be to use in-vivo preparations of tadpole and zebrafish as model systems to examine the development and activity dependent plasticity of retinotectal connections. Using double and triple patch recordings on intact animals it is possible to specifically look at the connection between one or two retinal ganglion cells and a postsynaptic tectal cell. Furthermore it is possible, other than in all hippocampus preparations, to use the natural stimulus (light) to activate presynaptic neurons and induce changes in synaptic efficacy. Since different forms of plasticity (LTP and LTD) can be specifically induced, the respective morphological correlates can be examined: precise temporal control over pre- and postsynaptic components enables the application of exact stimulus-protocols for the enhancement as well as the weakening of synaptic connections. To examine correlated morphological changes pre- and postsynaptic neurons are stained either via expression of fluorescent proteins or directly with a fluorescent dye via the patch-pipette and imaged online with a two-photon microscope. In order to get beyond the purely correlative evidence and to uncover causal connections between behaviour, synaptic activity and the molecular basis, synaptic and morphological plasticity will be compared between learning-mutants and wild-type zebrafish. Similar to the findings in Drosophila, also in Zebrafish it is to be expected that a significant number of the generated mutants will show defects in their learning behaviour. This offers an attractive basis to examine and correlate changes in learning behaviour on a molecular, cellular and behavioural level. Screens to identify learning mutants of this kind are planned as a second part of my future projects; the specific techniques to test embryonic fish for learning deficits will be developed in my laboratory, but the screen itself will of course have to be carried out in collaboration with one of the big Zebrafish facilities. Having found learning mutants it is then possible to go on and examine in how far synaptic and morphological plasticity is changed in these mutants with respect to the wild-type. Since the same rules seem to apply for the plasticity of retinotectal connections as for the learning-relevant plasticity in mammal-hippocampus, it is reasonable to assume that mutations which influence learning behaviour will also be reflected in the plasticity of the retinotectal system. I therefore hope to be able to establish and investigate an in vivo system in which learning and synaptic plasticity in vertebrates can be tightly correlated on the molecular, morphological, and systems level.
Selected Publications: Bruns D, Engert F, Lux HD (1993) A fast activating presynaptic reuptake current during serotonergic transmission in identified neurons of Hirudo. Neuron 10:559-572. Taschenberger H, Engert F, Grantyn R (1995) Synaptic current kinetics in a solely ampa receptor-operated glutamatergic synapse formed by rat retinal ganglion neurons. J.Neurophys. 74: Engert F, Paulus GG, Bonhoeffer T (1996) A low-cost UV laser for flash photolysis of caged compounds. J.Neurosci.Methods 66:47-54. Veselovsky NS, Engert F, Lux HD (1996) Fast local superfusion technique. Pflügers Arch. 432:351-354. Engert F, Bonhoeffer T (1997) Synapse specificity of long-term potentiation breaks down at short distances. Nature 388:279-284. Engert F, Bonhoeffer T (1999) Dendritic spine changes associated with hippocampal long-term synaptic plasticity. Nature 399:66-70. (selected breakthrough of the year in the neurosciences by Science magazine) Engert F, Tao HW, Zhang LI, Poo MM (2001) Emergence of Input Specificity of LTP in a Developing Retinotectal System. Neuron 31:569-580. F. Engert, H. W. Tao, L. I. Zhang, and M. M. Poo. (2002) Moving visual stimuli rapidly induce direction sensitivity of developing tectal neurons. Nature 419:470-475. |
