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1988-2013: 25 years since our discovery of gene expression in learning (click to read)

Head: Leszek Kaczmarek, Ph.D.

The team: Dr. Katarzyna Bieganska, Dr. Artur Czupryn, Dr. Magdalena Dziembowska, Dr. Adam Gorlewicz, Dr. Tomasz Jaworski, Dr. Katarzyna Kalita-Bykowska, Danylo Khomiak (PhD student), Paulina Koza (PhD student), Anna Krysiak (PhD student), Dr Adam Krzystyniak, Tomasz Lebitko (PhD student), Diana Legutko, Katarzyna Łepeta (PhD student), Julia Lopez, Hubert Madej (PhD student), Pawel Matryba, Karolina Nader, Dr Jewgeni Nikolajew, Dr Monika Pawlowska, Dr Barbara Pijet, Dr Rafal Platek, Dr Emilia Rejmak-Kozicka, Dr Izabela Rutkowska-Włodarczyk, Olga Sakharczuk (PhD student), Ahmad Salamian (PhD student), Dr Aneta Schaap-Oziemlak, Bogusia Sudoł-Rutkowska, Dr Anna Suska, Dr Marzena Stefaniuk, Marta Szychowska (PhD student), Behnam Vafadari (PhD student) Our research aim is to understand brain-mind connection. We believe that is is possible to localize specific mind functions into the brain and then reveal their molecular and cellular underpinnings. The window to understand mind is learning and memory that can be successfully studied in experimental animals. At the molecular and cellular levels , synaptic plasticity appears to provide plausible explanation for those phenomena. Twenty five years ago, together with H.J. Matthies and his colleagues from Magdeburg and simultaneously with K.V. Anokhin and his coworkers in Moscow, we have discovered gene expression in the mammalian brain in learning. The first such gene was c-fos, encoding a component of transcription factor AP-1. This led us to identify c-Fos/AP-1 such target genes in activated neurons as TIMP-1 (tissue inhibitor of matrix metalloproteinases) and MMP-9 (matrix metalloproteinase). Over the last dozen years we have shown that MMP-9 is produced and released at the excitatory synapses in response to enhanced neuronal activity to play a paramount role in the synaptic plasticity, learning and memory as well as in neuropsychiatric disorders, including epilepsy, alcohol addiction, schizophrenia and bipolar disorder. Presently, our major research effort is focused on MMP-9 and its fundamental role in controlling morphological and functional plasticity of the excitatory synapses, especially in the central nucleus of the amygdala, which we have implicated as pivotal for the appetitive learning.

Selected Publications

Stefaniuk M., Beroun A., Lebitko T., Markina O., Leski S., Meyza K., Grzywacz A., Samochowiec J., Samochowiec A., Radwanska K., Kaczmarek L. Matrix metalloproteinase-9 and synaptic plasticity in the central amygdala in control of alcohol seeking behavior. Biological Psychiatry, in press.

van der Kooij M. , Fantin M. , Rejmak E., Grosse J., Zanoletti O., Fournier C., Ganguly K., Kalita K., Kaczmarek L., Sandi C. Role for MMP-9 in stress-induced down-regulation of nectin-3 in hippocampal CA1 and associated behavioral alterations. Nature Communications., 5: 4995, 2014.

Stawarski M., Rutkowska-Wlodarczyk I., Zeug A., Bijata M., Madej H., Kaczmarek L., Wlodarczyk J. Genetically encoded biosensor for imaging MMP-9 activity. Biomaterials, 35: 1402-1410, 2014.

Janusz A., Milek J., Perycz M., Pacini L., Bagni C., Kaczmarek L., Dziembowska M. The Fragile X Mental Retardation Protein regulates Matrix Metalloproteinase 9 mRNA at synapses.  J. Neurosci., 33: 18234–1824, 2013.

Knapska E., Lioudyno V., Kiryk A., Gorkiewicz T., Mikosz M., Michaluk P., Gawlak M., Chaturvedi M., Mochol G., Balcerzyk M., Wojcik D.K., Wilczynski G.M., Kaczmarek L. Reward learning requires activity of matrix metalloproteinase-9 in the central amygdala. J. Neurosci., 33: 14591–14600, 2013.

Dziembowska M., Milek J., Janusz A., Rejmak E., Romanowska E., Gorkiewicz T., Tiron A., Bramham C., Kaczmarek L. Activity-dependent local translation of matrix metalloproteinase-9. J. Neurosci., 32: 14538 –14547, 2012.

Knapska E., Macias M., Mikosz M., Nowak A., Owczarek D., Wawrzyniak M., Pieprzyk M.,  Cymerman I.A., Werka T., Sheng M., Maren S., Jaworski J., Kaczmarek L., Functional anatomy of neural circuits regulating fear and extinction. Proc. Natl. Acad. Sci. USA, 42: 17093-17098, 2012.

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