NCN OPUS 2018/31/B/NZ4/01603: Deciphering activity of CA1 region during alcohol seeking and consumption (2019 - 2022); PI: Kasia Radwanska
Development of drug addiction involves functional alterations within brain areas controlling reward-driven behaviour and memory processes. In this context, remodelling of the glutamatergic synapses has gained a lot of attention (Hanse et al, 2013; Lüscher et al, 2011; Wolf, 2016). Still the molecular processes which contribute to the remodelling of the synapses and circuits in addicted individuals are poorly understood. Our aim in this project is to test the hypothesis that regulation of activity of CA1 pyramidal neurons by Arc/Arg3.1 protein controls addiction-related behaviours. Arc/Arg3.1 protein is rapidly upregulated by strong synaptic activity and critically contributes to weakening glutamatergic synapses by promoting AMPA receptor endocytosis (Plath et al, 2006; Tzingounis and Nicoll, 2006). The hypothesis is also based on our observations showing that Arc knockout mice (Arc KO) are impaired in alcohol seeking during relapse induced by alcohol-associated cues, while alcohol consumption and seeking in wild-type animals affects expression of Arc protein in the area CA1 of the hippocampus.
To verify the hypothesis we plan to realize the following tasks:
Task 1. To test the role of Arc/Arg3.1 in CA1 in regulation of addiction-related behaviours.
Task 2. To test the role of Arc/Arg3.1 in regulation of alcohol-induced plasticity of CA1 neurons.
Task 3. To test the dynamics of CA1 neurons during alcohol consumption and seeking.
NCN SYMFONIA 2013/08/W/NZ4/00691: Neuroengineering control and regulation of behavior (2013 - 2018); co-investigator: Kasia Radwanska
NCN OPUS 2015/19/B/NZ4/03163; Do silent synapses regulate alcohol relapse? (2016 - 2020); PI: Kasia Radwanska
Bio4Med Marie Sklodowska-Curie grant agreement No 665735, PhD project: Bio4Med - The role of Arc protein in the regulation of alcohol addiction-related behaviors (2015 - 2019)
NCN PRELUDIUM: Neuronal circuits and molecular mechanisms underlying alcohol seeking (2016-2019); PI: Anna Caly
NCN PRELUDIUM: Does acamprosate regulate generation of silent synapses in mice drinking alcohol? (2017-2019); PI: Maria Nalberczak-Skora
NCN PRELUDIUM: Do projections from nucleus reuniens to dorsal CA1 area control fear memory extinction? (2017-2019); PI: Magdalena Ziolkowska
HARMONIA NCN 2016/22/M/NZ4/00674: The role of dentate gyrus in the regulation of alcohol seeking during withdrawal (2017-2020); PI: Kasia Radwanska
NCN PRELUDIUM 2015/19/N/NZ4/03611: Neuronal correlates of long-term fear memory and its extinction (2016-2018); PI: Kacper Lukasiewicz
NCN SONATA BIS 2012/05/E/NZ4/02996: The role of alphaCaMKII autophosphorylation in structural spine plasticity: focus on memory and alcohol addiction (2013-2018); PI: Kasia Radwanska
NCN Harmonia 2013/08/M/NZ3/00861, The alternative mechanism for memory formation in old age, 2013-2016; PI: Kasia Radwanska
POMOST/2011-4/7 FNP grant powrotowy, Do multiinervated spines store memory? (2012-2015); PI: Kasia Radwanska
Grant MNiSW 2084/7.PREU/2011/2: Alpha CaMKII autophosphorylation as a mechanism to regulate alcohol consumption, 2009-2013 Katarzyna Radwanska
Marie Curie Actions- European Re-integration Grants (ERG), PERG05-GA-2009-247841, Alco_CaMK- Alpha CaMKII autophosphorylation as a mechanism to regulate alcohol consumption, 2009-2013; PI: Kasia Radwanska