PMID- 21401875
OWN - NLM
STAT- MEDLINE
DCOM- 20111007
LR  - 20220309
IS  - 1601-183X (Electronic)
IS  - 1601-183X (Linking)
VI  - 10
IP  - 4
DP  - 2011 Jun
TI  - VAChT knock-down mice show normal prepulse inhibition but disrupted long-term 
      habituation.
PG  - 457-64
LID - 10.1111/j.1601-183X.2011.00686.x [doi]
AB  - 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.
CI  - (c) 2011 The Authors. Genes, Brain and Behavior (c) 2011 Blackwell Publishing Ltd and 
      International Behavioural and Neural Genetics Society.
FAU - Schmid, S
AU  - Schmid S
AD  - Department of Anatomy and Cell Biology, Robarts Research Institute, Schulich 
      School of Medicine and Dentistry, University of Western Ontario, London, Ontario, 
      Canada. susanne.Schmid@schulich.uwo.ca
FAU - Azzopardi, E
AU  - Azzopardi E
FAU - De Jaeger, X
AU  - De Jaeger X
FAU - Prado, M A M
AU  - Prado MA
FAU - Prado, V F
AU  - Prado VF
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110315
PL  - England
TA  - Genes Brain Behav
JT  - Genes, brain, and behavior
JID - 101129617
RN  - 0 (Slc18a3 protein, mouse)
RN  - 0 (Vesicular Acetylcholine Transport Proteins)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/*metabolism
MH  - Acoustic Stimulation
MH  - Animals
MH  - Habituation, Psychophysiologic/*genetics
MH  - Mice
MH  - Mice, Knockout
MH  - Reflex, Startle/genetics
MH  - Sensory Gating/*genetics
MH  - Synaptic Transmission/genetics
MH  - Synaptic Vesicles/genetics/metabolism
MH  - Vesicular Acetylcholine Transport Proteins/*genetics/metabolism
EDAT- 2011/03/16 06:00
MHDA- 2011/10/08 06:00
CRDT- 2011/03/16 06:00
PHST- 2011/03/16 06:00 [entrez]
PHST- 2011/03/16 06:00 [pubmed]
PHST- 2011/10/08 06:00 [medline]
AID - 10.1111/j.1601-183X.2011.00686.x [doi]
PST - ppublish
SO  - Genes Brain Behav. 2011 Jun;10(4):457-64. doi: 10.1111/j.1601-183X.2011.00686.x. 
      Epub 2011 Mar 15.