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The main topic of our group is the study of the effects of
botulinum neurotoxins (BoNTs) in the brain. BoNTs (seven
serotypes, indicated A-G) are bacterial enzymes that block
transmitter release via the cleavage of specific components
of the vesicle fusion machinery. We recently found that BoNT/A
exhibits retrograde axonal transport following uptake at the
nerve terminal. This finding has implications for the
clinical uses of BoNT/A.
Our work demonstrates that BoNTs are powerful tools to block
neuronal communication in the brain for varying durations. We are exploiting the
silencing properties of BoNTs in different experimental
studies.
First, we are employing BoNTs to address the role of neural
activity during visual system development and plasticity. In
a recent study, we have shown that a BoNT/E-mediated,
transient unilateral silencing of rat striate cortex during
postnatal development has lasting effects on visual function
and plasticity. Indeed, visual abilities are permanently
reduced in the blocked hemisphere, and the critical period
for ocular dominance plasticity persists into adulthood.
Remarkably, these effects extend equally to the
contralateral uninjected side, revealing a role for
interhemispheric connections in cortical development.
Second, we have been evaluating the anticonvulsant and
antiepileptogenic properties of BoNT/E in rodent models of
temporal lobe epilepsy. Specifically, we have shown that
BoNT/E application to the hippocampus has anticonvulsant and
neuroprotective effects in rodent models of temporal lobe
seizures. |