Anatomically discrete functional effects of adenoviral clostridial light chain gene-based synaptic inhibition in the midbrain

Gene Therapy
Z ZhaoN M Boulis

Abstract

The gene for the Light Chain fragment of Tetanus Toxin (LC) induces synaptic inhibition by preventing the release of synaptic vesicles. The present experiment applied this approach within the rat midbrain in order to demonstrate that LC gene expression can achieve functionally and anatomically discrete effects within a sensitive brain structure. The deep layers of the superior colliculus/deep mesencephalic nucleus (dSC/DpMe) that are located in the rostral midbrain has been implicated in fear-induced increase of the acoustic startle reflex (fear potentiated startle) but exists in close proximity to neural structures important for a variety of critical functions. The dSC/DpMe of adult rats was injected bilaterally with adenoviral vectors for LC, green fluorescent protein, or vehicle. Synaptobrevin was depleted in brain regions of adenoviral LC expression. LC gene expression in the dSC/DpMe inhibited the increase in startle amplitude seen with the control viral infection, and blocked context-dependent potentiation of startle induced by fear conditioning. Although LC gene expression reduced the absolute amount of cue-specific fear potentiated startle, it did not decrease percent potentiated startle to a cue, nor did it reduce fear...Continue Reading

References

Aug 11, 2000·Toxicon : Official Journal of the International Society on Toxinology·O RossettoC Montecucco
Oct 12, 2002·Science·Jia LuoMatthew J During
Jan 15, 1955·Nature·V B BROOKSJ C ECCLES

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Citations

Jan 11, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jun YangNicholas M Boulis
Jul 19, 2011·Neurology Research International·Chalonda R HandyThais Federici
May 1, 2009·Neurosurgery·Jaimie M HendersonNicholas Boulis
Dec 2, 2020·Audiology Research·Annanya Soni, Abhishek Dubey

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