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About me

Dr. Marie Carlén is Associate Professor and group leader at the Department of Neuroscience.

Marie received her Ph.D. in medicine from Karolinska Institutet in 2005. Her doctoral studies were conducted in the laboratory of Professor Jonas Frisén and focused on stem cells and neurogenesis in the adult brain and spinal cord. Marie went to Massachusetts Institute for Technology (MIT), Boston, for postdoc studies in the laboratory of Professor Li-Huei Tsai at the Picower Institute for Learning and Memory. During her postdoc Marie investigated how the activity of inhibitory interneurons expressing parvalbumin (PV) relate to cortical oscillatory activities and cognitive functions. 

In 2010 Marie was recruited back to Karolinska Institutet, and her laboratory is investigating cellular and circuit underpinning of cognition and psychiatry, with a strong focus on inhibitory neurons.

Research description

Research focus

Cognition encompasses a range of mental abilities, including perception, attention, working memory, planning and decision making. Proper cognitive functions are thus essential for many aspects of our everyday life. Little is known about how the brain's networks perform cognitive processes, including the role of different neuronal subtypes. Cognitive processes have repetitively been correlated to oscillatory brain activities, and is has been suggested that cognitive functions depend on synchronization of neuronal activity within and/or between brain areas. Synchronization of neuronal activity depends on interplay between excitation and inhibition, and inhibitory interneurons releasing GABA are key players in this interplay. We could earlier show that cortical inhibitory interneurons expressing parv­albumin (PV) generate gamma oscillations (30-80 Hz) in vivo (Cardin J / Carlén M et al. 2009, 2010). Research in both humans and research animals indicate that the excitation/inhi­bi­tion balance and synchronization of brain activities are deficient in psychiatric disorders with cognitive dysfunctions, such as schizophrenia. Moreover, changes in inhibitory PV neurons have been repetitively documented in individuals affected by schizophrenia. Our work show that changes in PV neurons result in both aberrant oscillatory brain activity and deficient cognitive functions (Rudenko A et al. 2015, Carlén M / Meletis K et al. 2012). 

Attention is a central cognitive function affected in many neuropsychiatric disorders, including schizophrenia, Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder. Attention is crucial for our ability to organize thoughts and actions into meaningful behavior, and prefrontal cortex (PFC) directly influences attentional processing. During attention, oscillatory brain activity in the gamma range increases in PFC (and other cortical areas) but a causal link between gamma oscillations and attention has been missing. We could recently show that successful allocation of attention is characterized by increased activity of PV neurons and gamma oscillations in PFC, and that the PV neurons underlie PFCs control of attention (Kim et al. 2016). Our findings support the view that cortical PV neurons are key players in cognitive processes, and suggest that cell-type specific manipulations can be used for enhancement of cortical computations and cognition. This concept is very encouraging, but it also underscores that in order to understand the operations of the brain we need to understand the component cells by their functions.

We are currently investigating the local and long-range connectivity of PFC, and how specific circuitry influence activities within the PFC. Many of our studies are investigating aspects of attentional processing.  

 

Normal network functions in cognition

With electrophysiological recordings, opto­genetic manipulations and imaging in behaving mice and rats we are probing the contribution of specific neuronal subtypes to cognitive functions. We are especially interested in circuitry giving input to mPFC, including the raphe nuclei, thalamus and the cholinergic space.

 

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 modeling aspects of mental disorders as well as pharmacology and optogenetics.  

 

Therapies for mental disorders

The ultimate goal for our research is to identify cellular and molecular targets for pharmacological interventions in psychiatric disorders.

 

Publications systems neuroscience and circuits:

 

Prefrontal Parvalbumin Neurons in Control of Attention.

Kim H, Ährlund-Richter S, Wang X, Deisseroth K and Carlén M.

Cell. 2016 Jan 14.

Structural foundations of optogenetics: Determinants of channelrhodopsin ion selectivity.

Berndt A, Lee SY, Wietek J, Ramakrishnan C, Steinberg E, Rashid AJ, Kim H, Park S, Santoro A, Frankland PW, Iyer SM, Pak S, Ährlund-Richter S, Delp SL, Malenka RC, Jossely SA, Carlén M, Hegemann P and Deisseroth K. 

Proc Natl Acad Sci U S A. 2015 Dec 22. PMID:26699459

Loss of cyclin-dependent kinas 5 from parvalbumin interneurons leads to hyperinhibition, decreased anxiety, and memory impairment.

Rudenko A, Seo J, Hu J, Su SC, de Anda FC, Durak O, Ericsson M, Carlén M, Tsai LH.

J Neurosci. 2015 Feb 11;35(6):2372-83. PMID: 25673832

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):663-78.  PMID:25102561

Mice lacking NMDA receptors in parvalbumin neurons display normal depression-related behavior and response to antidepressant action of NMDAR antagonists.

Pozzi L, Dorocic IP, Wang X, Carlén M, Meletis K.

PLoS One. 2014 Jan 16;9(1):e83879. PMID: 24454710

Target selectivity of feedforward inhibition by striatal fast-spiking interneurons.

Szydlowski SN, Pollak Dorocic I, Planert H, Carlén M, Meletis K* / Silberberg G*.

J Neurosci. 2013 Jan 23;33(4):1678-83. PMID: 23345240

Optogenetic dissection of cortical information processing - shining light on schizophrenia.

Wang X, Carlén M.

Brain Res. 2012 Oct 2;1476:31-7. Review. PMID: 22578471

Chronically implanted hyperdrive for cortical recording and optogenetic control in behaving mice.

Siegle JH, Carlén M, Meletis K, Tsai LH, Moore CI, Ritt J.

Conf Proc IEEE Eng Med Biol Soc. 2011. 7529-32. PMID:22256080

A critical role for NMDA receptors in parvalbumin interneurons for gamma rhythm induction and behavior.

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.

Molecular Psychiatry. 2012 May;17(5):537-48.  PMID: 21468034

Neocortical interneurons: from diversity, strength.

Moore CI, Carlén M, Knoblich U, Cardin JA.

Cell. 2010 Jul 23;142(2):189-93. PMID: 20655460

Targeted optogenetic stimulation and recording of neurons in vivo using cell-type-specific expression of Channelrhodopsin-2.

Cardin JA* / Carlén M*, Meletis K, Knoblich U, Zhang F, Deisseroth K, Tsai LH, Moore CI.

Nature Protocols. 2010;5(2):247-54. PMID: 20134425

Driving fast-spiking cells induces gamma rhythm and controls sensory responses.

Cardin JA* / Carlén M*, Meletis K, Knoblich U, Zhang F, Deisseroth K, Tsai LH, Moore CI.

Nature. 2009 Jun 4;459(7247):663-7. PMID: 19396156

 

Publications stem cells and adult neurogenesis:

Efficient reprogramming of adult neural stem cells to monocytes by ectopic expression of a single gene. 

Forsberg M* / Carlén M *, Meletis K, Yeung MS, Barnabé-Heider F, Persson MA, Aarum J, Frisén J. 

Proc Natl Acad Sci U S A 2010. 107(33): 14657-61. PMID: 20675585

Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke. 

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.

Nature Neuroscience 2009. 12(3):259-67. PMID: 19234458

Spinal cord injury reveals multilineage differentiation of ependymal cells.

Meletis K* / Barnabé-Heider F* / Carlén M*, Evergren E, Tomilin N, Shupliakov O, Frisén J.

PLoS Biology 2008. 6(7):e182. PMID: 18651793

Genetic visualization of neurogenesis.

Carlén M, Meletis K, Barnabé-Heider F, Frisén J.

Exp Cell Res. 2006 Sep 10;312(15):2851-9. PMID: 16806169

Evidence for neurogenesis in the adult mammalian substantia nigra.

Zhao M* / Momma S*, Delfani K, Carlen M, Cassidy RM, Johansson CB, Brismar H, Shupliakov O, Frisen J, Janson AM.

Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7925-30.PMID: 12792021

Gene delivery to adult neural stem cells.

Falk A* / Holmström N*, Carlén M, Cassidy R, Lundberg C, Frisén J.

Exp Cell Res. 2002 Sep 10;279(1):34-9. PMID: 12213211

Functional integration of adult-born neurons.

Carlén M* / Cassidy RM*, Brismar H, Smith GA, Enquist LW, Frisén J.

Current Biololgy. 2002 Apr 2;12(7):606-8. PMID: 11937032

Academic honors, awards and prizes

European Research Council Starting Grant 2013, (LS5)
Wallenberg Academy Fellow in Medicine, 2012.
Ragnar Söderberg Fellow in Medicine, 2012. 
2012 Freedman Prize Honorable Mention for Outstanding Research in Basic Brain and Behavior Science. Brain & Behavior Research Foundation (former NARSAD).
Sven och Ebba-Christina Hagbergs Prize, 2010. 
NARSAD Young Investigator Award 2010
NARSAD Young Investigator Award 2008
PIIF: Picower Institute Innovation Fund 2007 (MIT; Cambridge, USA)
Keystone Symposium on Stem Cells. 2006 Scholarship Award of Excellence: The Alzheimer’s Association Route28 Summits in Neurobiology, 2001

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