Cognition encompasses an array of domains, including sensory processing, perception, attention and working memory. Proper cognitive functions are thus essential for most aspects in our everyday life. Cognition is changed in disorders such as schizophrenia and autism. Extensive evidence exists that cognitive functions depend on synchronization of neuronal activity within and between brain areas. Synchronization of neuronal activity depends on interplay between excitation and inhibition, and the inhibitory PV interneurons are key players in this interplay. Data support that the excitation-inhibition balance and synchrony is deficient in psychiatric disorders with cognitive dysfunctions.

The new technique optogenetics employs light to activate or inhibit neurons. Genetic targeting of light-sensitive proteins to selected neuronal populations enables detailed analysis of their role in brain processes and behaviors. We are using optogenetics to establish the physiological and cellular basis for cognition, focusing on attention and working memory. With the use of Cre-loxP strategies, we are manipulating the PV interneurons in prefrontal cortex during attention and working memory tasks, and analyze the effects on synchronization of brain activity and cognitive performance in the tasks. We hope that this strategy will not only decipher cognition, but also let us establish cellular underpinnings of dysfunctional cognitive functions and behavioral changes in psychiatric disorders.

Normal network functions
With electrophysiology recordings and optogenetic manipulations in behaving animals we are probing the contribution of specific neuronal subtypes to cogntivite functions. Our projects include attentional and working memory tasks, investigating local and global synchronies and their effects on behaviors.

Mechanisms underlying psychiatric disorders
Ongoing research in the lab aims to understand how brain activity and neuronal networks are affected or altered in psychiatric disorders such as schizophrenia. We are using transgenic animals modelling aspects of mental disorders as well as optogenetics to change brain activity and probe the effects with recordings and behavior.

Therapies for mental disorders
There is a severe lag in psyciatric medicine, much due to a lack of understanding of the brain and it actvitities. An ultimate goal for our research is therefore to use our findings to identify new cellular and molecular targets for pharmacological interventions in psychiatric disorders.

5 Selected Publications

Szydlowski SN., Pollak Dorocis I., Planert H., Carlén M., Meletis K., Silberberg G. (2013) Target selectivity of feedforward inhibition by striatal fast-spiking interneurons. J. Neurosci., 33 (4) : 1678-83.

Carlén M., Meletis K., Siegle JH., Cardin JA., Futai K., Vierling-Claassen D., Rühlmann C., Jones SR., Deisseroth K., Sheng M., Moore CI., Tsai LH. (2012) A critical role for NMDAR in parvalbumin interneurons for gamma oscillations and behavior. Mol. Psychiatry, 17 (5) : 537-48.        

Cardin JA., Carlén M., Meletis K., Knoblich U., Zhang F., Deisseroth K., Tsai LH., Moore CI. (2010) Targeted optogenetic stimulation and recording of neurons in vivo using cell-type-specific expression of Channelrhodopsin-2. Nature Protoc., 5 (2) : 247-54.            

Cardin JA., Carlén M., Meletis K., Knoblich U., Zhang F., Deisseroth K., Tsai LH., Moore CI. (2009) Driving fast-spiking cells induces gamma rhythm and controls sensory responses. Nature, 459 (7247) : 663-7.
    
Carlén M., Meletis K., Göritz C., Darsalia V., Evergren E., Tanigaki K., Amendola M., Barnabé-Heider F., Yeung MS., Naldini L., Honjo T., Kokaia Z., Shupliakov O., Cassidy RM., Lindvall O., Frisén J. (2009) Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke. Nat. Neurosci., 12 (3) : 259-67.

Awards, Fellowships and Honours

2013            ERC Starting Grant
2012            Wallenberg Academy Fellow, selected as 1 of 8 in Medicine in Sweden (for 5 years)
2012            Ragnar Söderberg Fellow in Medicine 2012, selected as 1 of 8 in Sweden (for 5 years)
2012            Freedman Prize Honorable Mention for Outstanding Research in Basic Brain and Behavior Science, Brain & Behavior Research Foundation
2010            Sven and Ebba-Christina Hagbergs Prize 2010, Karolinska Institute
2010            Assistant Professorship from Swedish Research Council (VR), ranked 1st out of 258 applicants
2010            Vinnova: VINNMER Marie Curie International Qualification
2010            NARSAD Young Investigator Award
2008            NARSAD Young Investigator Award
2007            PIIF (Picower Institute Innovation Fund), MIT, Cambridge, USA
2006            Keystone Symposium on Stem Cells Scholarship
2001            Award of Excellence: The Alzheimer’s Association Route28 Summits in Neurobiology

• Neural network functions
• In vivo optogenetics
• Cognition
• Behaviour
• Pathophysiology of psychiatric disorders
• Adult neural stem cells and neurogenesis