Disturbances in the neuronal circuits of the limbic system are found in neuropsychiatric disorders such as major depression and in the development of addiction. Surprisingly little is known about the specific functional role of each neuronal subtype within the limbic circuits during reward-related behaviors and for addiction. The main limitation for the proper in vivo investigation of the limbic system has been the lack of specificity in manipulation of functionally distinct neuronal subtypes. The genetic and optogenetic approach our laboratory has established allows for the direct characterization of neuronal subtypes responsible for distinct aspects of animal behaviors through specific modulation of neuronal activity in genetically defined neuronal populations with very high temporal precision. Our multidisciplinary approach is based on the combination of techniques from molecular neuroscience, mouse genetics, optogenetics, systems neuroscience, in vivo electrophysiology and animal behavior. We also characterize the synaptic inputs, both local and long-range, that regulate the function of specific neuronal subtypes using a genetically modified rabies virus method, combining the specificity of genetic transsynaptic tracing of connections with in vivo optogenetic manipulation. Our research can provide a rational foundation for development of new therapeutic strategies that specifically target discrete neuronal populations within the limbic system for treatment of reward and mood disorders.
For further information, please also see: http://ki.se/en/neuro/meletis-laboratory
Pollak Dorocic I, Fürth D, Xuan Y, Johansson Y, Pozzi L, Silberberg G, Carlén M, Meletis K. (2014) A whole-brain atlas of inputs to serotonergic neurons of the dorsal and median raphe nuclei. Neuron, 83(3):663-78.
Szydlowski S., Pollak Dorocic I., Planert H., Carlén M., Meletis K., Silberberg G. (2013) Target selectivity of feed-forward inhibition by striatal fast-spiking parvalbumin expressing interneurons. J. Neurosci. , 33 (4) : 1678-83.
Song S., Zhong C., Bonaguidi M., Sun G., Hsu D., Huang Z., Gu Y., Meletis K., Ge S., Enikolopov G., Deisseroth K., Luscher B., Christian K., Ming G., Song H. (2012) Neuronal circuitry mechanism regulating adult quiescent neural stem cell fate decision. Nature , 489 (7414) : 150-4.
Carlén M., Meletis K., Siegle J., Cardin J., Futai K., Vierling-Claasen D., Ruhlmann C., Jones S., Deisseroth K., Sheng M., Moore C., Tsai LH. (2012) A critical role for NMDA receptors in parvalbumin interneurons for gamma rhythm induction and behavior. Mol. Psychiatry , 17(5) : 537-48.
Cardin JA., Carlén M., Meletis K., Knoblich U., Zhang F., Deisseroth K., Tsai LH., Moore C. (2009) Activation of fast spiking interneurons induces gamma oscillations and shapes sensory transmission. Nature , 459 (7247) : 663-7.
2011 William K. Bowes Jr. Foundation Assistant Professor Award
2010 Marie Curie Reintegration Grant FP7/EU
2010 NARSAD Young Investigator Award (USA)