TY - JOUR
T1 - RIM1α and interacting proteins involved in presynaptic plasticity mediate prepulse inhibition and additional behaviors linked to schizophrenia
AU - Blundell, Jacqueline
AU - Kaeser, Pascal S.
AU - Südhof, Thomas C.
AU - Powell, Craig M.
PY - 2010/4/14
Y1 - 2010/4/14
N2 - Several presynaptic proteins involved in neurotransmitter release in the CNS have been implicated in schizophrenia in human clinical genetic studies, in postmortem studies, and in studies of putative animal models of schizophrenia. The presynaptic protein RIM1α mediates presynaptic plasticity and cognitive function. We now demonstrate that mice deficient in RIM1α exhibit abnormalities in multiple schizophrenia-relevant behavioral tasks including prepulse inhibition, response to psychotomimetic drugs, and social interaction. These schizophrenia-relevant behavioral findings are relatively selective to RIM1α-deficient mice, as mice bearing mutations in the RIM1α binding partners Rab3A or synaptotagmin 1 only show decreased prepulse inhibition. In addition to RIM1α's involvement in multiple behavioral abnormalities, these data suggest that alterations in presynaptic forms of short-term plasticity are linked to alterations in prepulse inhibition, a measure of sensorimotor gating.
AB - Several presynaptic proteins involved in neurotransmitter release in the CNS have been implicated in schizophrenia in human clinical genetic studies, in postmortem studies, and in studies of putative animal models of schizophrenia. The presynaptic protein RIM1α mediates presynaptic plasticity and cognitive function. We now demonstrate that mice deficient in RIM1α exhibit abnormalities in multiple schizophrenia-relevant behavioral tasks including prepulse inhibition, response to psychotomimetic drugs, and social interaction. These schizophrenia-relevant behavioral findings are relatively selective to RIM1α-deficient mice, as mice bearing mutations in the RIM1α binding partners Rab3A or synaptotagmin 1 only show decreased prepulse inhibition. In addition to RIM1α's involvement in multiple behavioral abnormalities, these data suggest that alterations in presynaptic forms of short-term plasticity are linked to alterations in prepulse inhibition, a measure of sensorimotor gating.
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U2 - 10.1523/JNEUROSCI.0328-10.2010
DO - 10.1523/JNEUROSCI.0328-10.2010
M3 - Article
C2 - 20392954
AN - SCOPUS:77950970508
SN - 0270-6474
VL - 30
SP - 5326
EP - 5333
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 15
ER -