The title of my talk: Alcohol memories are controlled by Arc/Arg3.1.
Abstract: Alcohol addiction is characterised by compulsive alcohol taking and seeking. Even after long-periods of abstinence addicted individuals tend to relapse upon exposure to context, or simple cues, associated with alcohol, leading new bouts of uncontrolled alcohol consumption and progression of disease. Thus understanding neuronal circuits involved in relapsing behaviour may be crucial to support abstinence. Arc/Arg3.1 protein is involved in the regulation of cognitive flexibility and activity of the glutamatergic system due to control over AMPA receptor endocytosis. Since plasticity of the glutamatergic synapses has been linked with addiction we hypothesised that Arc protein regulates alcohol addiction-related behaviours. To test this hypothesis we conduced longitudinal study in the automated IntelliCages to test addiction-related behaviour in Arc KO mice. We observed that Arc KO mice are more persistent in alcohol seeking during relapse induced by alcohol-associated cues than WT animals. Furthermore, we found that Arc protein is upregulated at the synapses of Central Amygdala (CeA) (but not DG or CA1 of the hippocampus) upon withdrawal from long-term alcohol drinking and this is accompanied by decreased ratio of AMPAR/NMDAR currents in BLA-to-CeA pathway. Local deletion of Arc in CeA with CrispR/Cas9 system resulted in enhanced alcohol seeking during cue-induced relapse and prevented downregulation of AMPAR/NMDAR currents in Arc KO cells. In conclusions, our data show the novel role of Arc protein in CeA, as a specific regulator of alcohol seeking during relapse induced by alcohol-associated cues.
Bio: Kasia Radwańska is a head of the Laboratory of Molecular Basis of Behaviour, Nencki Institute, Poland. She finished two postdoctoral fellowships, one at the Laboratory of Molecular Analysis of Memory of Prof. Karl Peter Giese (Marie Curie fellow 2006-2008), second at the Laboratory of Molecular Neurobiology of Prof. Leszek Kaczmarek (2008-2013). Dr Radwańska is honored by prestigious award from Polish Prime Minister for the Outstanding Habilitation (2013), Foundation for Polish Science POMOST grant for women (2010) and Marie Curie Reintegration Grant (2009).
Memory processes, including memory formation or extinction, are fundamental for brain function and they are affected in various psychiatric illnesses such as post-traumatic stress disorder or addiction. Currently, the molecular basis of memory processes is not sufficiently well understood to develop successful treatments for memory dysfunctions. Her team is studying molecular basis of memory processes. For experiments her team use transgenic mice, which allows to combine molecular and morphological analyses with behavioral studies. In particular Radwańska’s lab is interested in modeling alcohol addiction and cognitive impairments in laboratory animals. Toward this end they apply both behavioral analysis of transgenic mice in the IntelliCage system as well as patch clamp electrophysiology, confocal, electron and correlative 3D microscopy to study molecular, functional and structural alterations in different brain regions.
The long-term aim to her research is to develop insights for treatments for memory dysfunctions in psychiatric illnesses.