Effects of transcranial magnetic stimulation on limbic network properties in rat models of psychiatric phenotype

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The findings of human studies indicate that repetitive transcranial magnetic stimulation (rTMS) bears the potential to correct pathological neuronal activity associated with a spectrum of psychiatric diseases. Depending on the stimulus pattern (frequency, temporal structure) applied, cortical excitability can be raised or decreased. Little is know about the cellular effects of rTMS but numerous human and animal studies indicate an involvement of synaptic plasticity. However, since acute stimulation effects rarely last longer than 60 minutes, a direct induction of long-term potentiation or depression (LTP, LTD) is less likely than the induction of metaplasticity via homeostatic processes. Currently, a modulation of the cortical balance of excitation and inhibition via changes of the activity of GABAergic interneurons is discussed, in particular a regulation of LTP/LTD induction by disinhibition as is also discussed for natural processes of learning and activity driven development. Our own studies showed rTMS-induced modulation of the activity of cortical inhibitory interneurons, in particular those expressing the calcium binding protein parvalbumin (PV+) and belonging to the group of fast-spiking interneurons. Just the latter appear to play a key role in the development and persistence of neuropsychiatric diseases. Using electrophysiological, optical, pharmacological and immunhistochemical methods we like to study how neuronal excitability and plasticity and network activity may be altered in rat models of psychiatric phenotypes and how rTMS is able to change these processes in comparison to normal control rats. In addition, response properties of pre-labeled PV+ interneurons will be studied. In parallel we will further develop a system allowing the acute suprathreshold magnetic stimulation of brain slices while recording network activity induced by different orientations of the induced electric field. In the course of the planed studies we expect important findings regarding the kind of network activity induced by rTMS in vivo, whether they differ between pathological and healthy tissue and how the changes induced by rTMS may be beneficial to correct neuronal activity in a way to treat or prevent the progress of neuropsychiatric diseases.