Projekte: Entwicklungsbiologie psychiatrischer Störungen

A long-standing behavioral, pharmacological, and electrophysiological literature relates dopamine (DA) to reinforcement learning and reward prediction. In particular the phasic firing of DA midbrain neurons has been interpreted as an important learning signal that may drive adaptive processes in DA-innervated target regions. These processes are also thought to be of major clinical relevance in addiction, posttraumatic stress and anxiety disorders. One of the major DA target areas is the medial prefrontal cortex (mPFC) which itself has been implicated in associative rule learning and extinction. DA is known to modulate long-term-potentiation and -depression in the mPFC, but only very few studies so far have dealt with DA-modulation of spike-timing-dependent plasticity (STDP), a relatively recent phenomenon of particular relevance to associative learning theories. While previous studies were mainly performed in juvenile animals and with tonic pharmacological stimulation of DA receptors, here we aim to investigate DA-modulation of STDP at prefrontal cortico-cortical connections between pyramidal cells and interneurons in adult preparations in vitro. To overcome previous limitations in selectively and phasically stimulating DA fibers into the mPFC, optogenetic tools will be used. The putative role of the recently discovered parallel or co-release of glutamate from VTA neurons will be studied as well. The experimental findings will be translated into a formal STDP rule which will be further explored in biophysical neural network simulations for its role in mPFC-mediated associative and extinction learning. Computational predictions will be fed back into experimental design. Thus, by combining slice-electrophysiological, optogenetic, and neuro-computational methods we aim to gain deeper insights into the role of phasic DA signals in regulating synaptic plasticity, associative and extinction learning.