Brain circuits display great functional diversity as a result of the wide range of neuronal subtypes, each subtype with unique properties and connections. Disturbances in the limbic system are found in neuropsychiatric disorders that display changes in reward and mood processes. The activity of circuits that guide emotional and cognitive behaviors is determined by GABAergic interneurons that determine circuit function through temporally and spatially defined inhibition. It is therefore critical to functionally characterize GABAergic interneurons in order to describe how the limbic system shapes reward-related behavior and how limbic dysfunction can lead to mood disorders.
We therefore study how specific GABAergic interneuron subtypes regulate limbic circuits in vivo, and importantly, how that translates into control of animal behavior, using a variety of experimental approaches including transgenic animals, viruses, optogenetics, electrophysiology and behavioral assays. We study the connectivity patterns between neuronal subtypes using genetically modified viruses that display transsynaptic retrograde spread, to express fluorescent markers (GFP) or different types of light-sensitive opsins (ChR2), allowing us to map the anatomical and functional properties of circuits. Our long-term vision is to provide a detailed understanding of circuit function as determined by activity of GABAergic interneurons, ultimately providing us with a rational basis to develop new pharmacotherapies for mood disorders.
1. Optogenetic control of a Parvalbumin-expressing GABAergic interneuron.
2. Circuit and behavior control through electronic interface board with LED and gyroscope.
3. Corticostriatal circuit dissection with genetically modified viruses.
A Whole-Brain Atlas of Inputs to Serotonergic Neurons of the Dorsal and Median Raphe Nuclei.
Pollak Dorocic I, Fürth D, Xuan Y, Johansson Y, Pozzi L, Silberberg G, Carlén M, Meletis K.
Neuron. 2014 Aug 6;83(3):663-678. doi: 10.1016/j.neuron.2014.07.002.
Target selectivity of feedforward inhibition by striatal fast-spiking interneurons.
J. Neurosci. 2013 Jan;33(4):1678-83
A critical role for NMDA receptors in parvalbumin interneurons for gamma rhythm induction and behavior.
Mol. Psychiatry 2012 May;17(5):537-48
Driving fast-spiking cells induces gamma rhythm and controls sensory responses.
Nature 2009 Jun;459(7247):663-7
Daniel Furth - PhD student
Iakovos Lazaridis - Postdoc
Konstantinos Meletis - Associate Professor
Iskra Pollak Dorocic - PhD student
Laura Pozzi - Postdoc
Rania Tzortzi - PhD Student
Antje Märtin - PhD Student
Marc Parent - Postdoc