Imaging dopamine's role in timing-based corticostriatal synaptic plasticity

• Applicant: Dr. Verena Pawlak
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2005 to 2007
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 17607837

The highest levels of the neuromodulator, dopamine, are found in the striatum which is the major basal ganglia input structure, receiving excitatory projections from almost the entire cerebral cortex. Dysfunction of this corticostriatal pathway is thought to give rise to disorders such as Parkinson¿s disease and attention deficit hyperactivity disorder (ADHD) and dopamine is thought to be central to this dysfunction. Recently, activity dependent synaptic plasticity of the corticostriatal pathway has been shown to depend upon dopamine receptor activation. These studies of plasticity in the striatum have used induction protocols such as high frequency afferent stimulation, which are unlikely to occur in the intact brain, so it is therefore not known if plasticity exists under in vivo conditions. One of the major recent conceptual and experimental breakthroughs has been the discovery that more physiological patterns of neuronal activity are able to induce bidirectional changes in the efficacy of many cortical and hippocampal synapses. Given that the basic cellular prerequisites for this more physiological form of synaptic plasticity have recently been shown to be also available in the striatal neurons, we propose to combine patch clamp recordings in acute brain slices and two photon calcium imaging techniques to investigate if this form of plasticity plays a role in the striatum and what dopamine¿s involvement is. This would potentially link neuronal activity patterns found in vivo with the concept of synaptic plasticity and elucidate dopamine¿s influence on the outcome of these activity patterns, thereby in the long run enhancing our knowledge about dopamine-based states of disease.

• DFG Programme: Research Fellowships
• International Connection: Switzerland
• Host: Dr. Jason Kerr