Associate Professor
M.D., Medical School of Charles University, Prague, 1991
Ph.D., SUNY Downstate Brooklyn, 1995 

Neurobiology of autism and schizophrenia; gene expression-based mapping of brain activity; anatomical mapping of brain connectivity; high throughput microscopy

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The brain is composed of distinct neural circuits that can be classified by the type of neurotransmission (e.g. excitatory, inhibitory, and modulatory), anatomical connectivity (e.g. cortico-cortical and cortico-subcortical), and system function (e.g. sensory, motor, and associative).  Autism, schizophrenia and other psychiatric disorders are likely caused by subtle disruptions in some of these circuits, but our understanding of which circuits are affected is rudimentary at best.
 

We focus on the identification and analysis of brain regions, neural circuits and connectivity pathways that are disrupted in mouse models of autism and schizophrenia. Our approach is based on building a “pipeline” of anatomical and functional methods for analysis of neural circuits. We hypothesize that: 1) a systematic comparison of many genetic mouse models will allow us to determine overlaps in pathology - core dysfunctions of neural circuitry - responsible for the manifestation of neuropsychiatric disorders; and 2) neural circuit-based classification of autism and schizophrenia will provide key circuit targets for detailed mechanistic studies and therapeutic development.

An important part of our methodology is high-throughput microscopy for whole mouse brain imaging . Other methods include viral vector-based anatomical tracing, transgenic and knock-in “indicator” mouse lines for monitoring expression of activity-regulated genes, and both in vitro and in vivo two-photon imaging and electrophysiology.

 

Selected Publications

Broser, P., Erdogan, S., Grinevich, V., Osten, P., Sakmann, B., and Wallace, D.J. 2008. Automated axon length quantification for populations of labelled neurons. J. Neurosci. Methods 169: 43–54.

Cetin, A., Komai, S., Eliava, M., Seeburg, P.H. and Osten, P. 2007. Stereotaxic gene delivery in the rodent brain. Nat. Protoc. 1: 3166 ­– 3173.

Komai, S., Licznerski, P., Cetin, A., Waters J., Denk, W., Brecht, M. and Osten P. 2006. Postsynaptic excitability is necessary for strengthening of cortical sensory responses during experience-dependent development. Nat. Neurosci. 9: 1125–1133.

Grinevich, V., Brecht, M., and Osten, P. 2005 Monosynaptic pathway from rat vibrissa motor cortex to facial motor neurons revealed by lentivirus-based axonal tracing. J. Neurosci. 25: 8250­–8258.

Dittgen, T., Nimmerjahn, A., Komai, S., Waters, J., Margrie, T.W., Helmchen, F., Denk, W., Brecht, M. and Osten, P. 2004 Lentivirus-based genetic manipulations of cortical neurons and their optical and electrophysiological monitoring in vivo. Proc. Natl. Acad. Sci. USA 101: 18206–18211.