Painting memory engram by biologically active messengers –The molecular time travel for the search of memory

Abstract

Using MRI and PET methods, neuroscience has made significant progress in understanding the episodic events of the human brain under varied cognitive situations throughout the last century. However, the higher resolutions of the memory locus, which consists of a neuro-glial ensemble for episodic memory, are unclear and must be clarified. Additionally, attempts have been made to create new nano technologies for mapping complete brains and related engrams with single neuro-glial accuracy and resolution in the hopes of unlocking the secrets of the brain by delving into Brain Activity Map (BAM). This hypothetical research is the first of its kind to suggest a novel method for understanding episodic memory in mouse brains by mapping brain activity at the functional connectome (engram) level and focused on neuro-glia-ECM (Extracellular Matrix). I propose to paint the memory engram at the neuro glia-ECM canvas of the mouse brain by engineering and inserting novel "Biologically Active Messengers: Bidirectional Messengers (BM)s/ Alternative Clones (AC)s and Transcriptional/ Translational Messenger (TM)s" coupled with different colour tags into transgenic mice via Transposon and Recombination, followed by behavioural analysis and Clarity. The BMs will be produced in all neuro-glial cells via a bicistronic promoter (Neuro-glia specific promoter + Tetracycline Responsive Element) led by a tetracycline transactivator gene driven by an immediate early gene (c-Fos/ Arc), whereas the TMs will be expressed via an endogenous promoter. The viability of all constructions (BMs, ACs, and TMs) as well as the process of painting will be tested in cortical/ hippocampal culture by chemically generating long term potentiation (cLTP). Fear consolidation (Fear context and Recall by contextual cue) tests will be administered to adult transgenic mice, followed by Clarity coupled Immunostaining to investigate the neuro-glia-ECM ensemble after whole brain imaging using a Light Sheet Microscope. Finally, the steady state behaviour of normal mice will be compared to the episodic picture of a colourful painted engram. At both the functional connectome and activity levels, this holistic painting method will highlight cognition over multiple timelines of a working memory region. Bidirectional Messenger (Biological Boomerang) has huge implications in neuropsychiatric illness, generation of artificial blood, cancer treatment, and regenerative medicine in the near future, according to my intuition.