Research in our laboratory is primarily directed towards understanding the cellular and molecular mechanisms of synaptic integration, synaptic plasticity, neuronal excitability and how dopamine modulates these fundamental processes. We have focused our attention on neurons and synapses in the prefrontal cortex, an area of the brain that plays an important role in working memory, planning and emotions. Prefrontal cortex is also of interest because this brain region, and its interaction with the neurotransmitter dopamine, are strongly implicated in some psychiatric diseases (e.g. schizophrenia). Our experimental methods include local and rapid application of neurotransmitters (glutamate & dopamine), electrophysiology (patch-clamp recordings), fast simultaneous multi-site imaging of the dendritic tree (calcium-sensitive dyes & voltage-sensitive dyes), computer simulations (NEURON), neuron tracing and immunolabeling.

Drugs that block dopaminergic receptors have been shown to alleviate some symptoms in schizophrenia. On the other hand, drugs that stimulate dopamine receptors produce schizophrenic symptoms in healthy people. These two facts have prompted scientist to postulate that neurotransmitter dopamine is intimately related to higher psychic functions (understanding, planning, interacting with others). Several decades ago experiments in non-human primates have shown that optimal dopaminergic transmission is absolutely necessary for normal cognitive function (Brozoski et al., 1979). In spite an extensive research effort that lasted for over 25 years, it is still not clear how exactly the release of dopamine affects neuronal networks and individual nerve cells.

We are investigating the cellular effects of dopamine-receptor activation in the mammalian cortex. We have recently used fluorescence imaging techniques and patch-clamp recordings to analyze AP-evoked and glutamate-evoked influx of calcium ions into different parts of the pyramidal dendritic tree. We are currently measuring how dopamine receptor stimulations change dendritic calcium concentration. Calcium ions are important messengers that link electrical and biochemical processes in the central nervous system. We hope that these investigations will enhance our understanding of the brain function and explain disturbances in brain function which lead to schizophrenia.