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Microcircuitory of neocortex in context of neurodegenerative diseases is vaguely defined. Regarded as an issue of public
health, neural degeneration in Alzheimerâ??s is still feebly understood ascribing to its profoundly complex microcircuitory.
Several attempts have been made to decipher various microneuronal pathways with the help of viral tracers like adenoassociated
virus, herpes simplex virus and many more, one such virus being VSV, owing to its relatively low virulence in
humans with rapid replication cycle and ease of delivery. We will hypothesize the use of VSV to study neural degeneration,
elucidate the microcircuitory involved and the minute receptor expression polymorphisms associated with cortical neurons in
case of susceptible cohorts for early and differential diagnosis. Pseudotyping VSV and substituting its G protein with that of a
laboratory â??fixedâ? strain of rabies virus, namely, CVS II (Ugolini, 2011) and introducing luciferase tagging for efficient tracing
of infected neurons will enable it to travel transsynaptically in a retrograde fashion across cortical neurons. The pseudotyped
VSV may target and infect neurons actively displaying the nACh receptor, whose surface expression tends to decrease with
progression of Alzheimerâ??s in affected cohorts. Metabolic viability of infected neurons could be maintained by manipulating
the pseudotyped VSVâ??s polymerases to decrease the rate of its replication in a highly regulated time frame. Decrease in the
nAChR expression may help us to determine the extent of viral tracer infection in targeted neurons as well as establish a
relation between receptor expression and disease progression to determine Alzheimerâ??s mircocuitory pathway.