Behavioural tagging: Effect of novelty exploration on plasticity related molecular signatures

Abstract

Learning and memory are one of those frontier areas of neurobiology which attract us to investigate the intricacy of this process. Here, we aimed to investigate the general mechanism of "Behavioural Tagging and Capture" in long term memory (LTM) formation and to find the key factors playing role in consolidation of LTM. In this study, we've shown that not only plasticity related proteins (PRPs) but neurotransmitters and immediate early genes (IEGs) also play an important role in memory formation process. It's very well evident that memory traces can last longer if close in time novelty is introduced around memory encoding. Here our results point out that this novelty exploration acts as a modulator in memory consolidation by providing PRPs such as brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), enhancing neurotransmitters (Dopamine), IEGs (cFos) and some enzymes such as acetylcholinesterase (AChE), monoamine oxidase (MAO), sodium-potassium ATPase (Na⁺K⁺-ATPase). Therefore, by using a Novel Object Recognition task (NOR) in combination with novel task exposure, we evaluated the role of molecular markers in memory consolidation employing a behavioural tagging model. The purpose of the current study was first to evaluate the effect of novelty exposure around a single trail of NOR task in a critical time window on memory consolidation in rats after 24 h and second to determine the expression of BDNF, CREB, c-fos, AChE, MAO, Na⁺K⁺-ATPase as potential markers in the medial prefrontal cortex (mPFC) during memory formation. In the present study, to identify and validate the role of these molecular signatures in memory consolidation, infusion of the protein synthesis inhibitor Anisomycin (Ani) was done around the training session that causes a deficit in the formation of LTM when tested 24 h after weak encoding. Altogether, here we are providing the first comprehensive set of evidences indicating that BDNF, CREB, dopamine, some enzymes and c-fos role in modulating LTM by employing behavioural tagging model.

Keywords: Anisomycin; Behavioural tagging; Long term memory; Plasticity related proteins; Prefrontal cortex.