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VAChT knock-down mice show normal prepulse inhibition but disrupted long-term habituation
  • S. Schmid, Western University
  • E. Azzopardi, Western University
  • X. De Jaeger, Western University; Universidade Federal de Minas Gerais
  • Marco Prado
  • V. F. Prado, Western University
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The neurotransmitter acetylcholine (ACh) plays a crucial role in both the central and peripheral nervous system. Central cholinergic transmission is important for cognitive functions and cholinergic disruptions have been associated with different neural disorders. We here tested the role of cholinergic transmission in basic cognitive functions, i.e. in prepulse inhibition (PPI) and short-term habituation (STH) as well as long-term habituation (LTH) of startle using mice with a 65% knockdown (KD) of the vesicular ACh transporter (VAChT). These mice are slow in refilling cholinergic synaptic transmitter vesicles, leading to a reduced cholinergic tone. Prepulse inhibition has been assumed to be mediated by cholinergic projections from the midbrain to the reticular formation. Surprisingly, PPI and STH were normal in these mice, whereas LTH was disrupted. This disruption could be rescued by pre-testing injections of the ACh esterase inhibitor galantamine, but not by post-testing injections. The lack of a PPI deficit might be because of the fact that VAChT KD mice show disruptions mainly in prolonged cholinergic activity, therefore the transient activation by prepulse processing might not be sufficient to deplete synaptic vesicles. The disruption of LTH indicates that the latter depends on a tonic cholinergic inhibition. Future experiments will address which cholinergic cell group is responsible for this effect.


This is a draft of the Author Accepted Manuscript.

Citation Information
S. Schmid, E. Azzopardi, X. De Jaeger, Marco Prado, et al.. "VAChT knock-down mice show normal prepulse inhibition but disrupted long-term habituation" GENES BRAIN AND BEHAVIOR Vol. 10 Iss. 4 (2011) p. 457 - 464
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