Early motor development is abnormal in complexin 1 knockout mice

Glynn, Dervila; Sizemore, Rachel J.; Morton, A. Jennifer

doi:10.1016/j.nbd.2006.10.011

Cited by 35 publications

(29 citation statements)

References 56 publications

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“…However, some reduction in general locomotor activity was seen in mutant mice, which is likely to be the first signs of the ataxia that is more clearly observed at 4–5 weeks of age. Interestingly, a detailed developmental study of the complexin-I knockout mouse has been carried out (41). These mice display ataxia as early as P7, which understandably affected motor control and exploration although additional neurodevelopmental milestones were also altered, including those related to sensory behaviour.…”

Section: Discussionmentioning

confidence: 99%

Interaction between environmental and genetic factors modulates schizophrenic endophenotypes in the Snap-25 mouse mutant blind-drunk

Oliver

Davies

2009

Human Molecular Genetics

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To understand the pathophysiology of neuropsychiatric disorders such as schizophrenia requires consideration of multiple genetic and non-genetic factors. However, very little is known about the consequences of combining models of synaptic dysfunction with controlled environmental manipulations. Therefore, to generate new insights into gene–environment interactions and complex behaviour, we examined the influence of variable prenatal stress (PNS) on two mouse lines with mutations in synaptosomal-associated protein of 25 kDa (Snap-25): the blind-drunk (Bdr) point mutant and heterozygous Snap-25 knockout mice. Neonatal development was analysed in addition to an assessment of adult behavioural phenotypes relevant to the psychotic, cognitive and negative aspects of schizophrenia. These data show that PNS influenced specific anxiety-related behaviour in all animals. In addition, sensorimotor gating deficits previously noted in Bdr mutants were markedly enhanced by PNS; significantly, these effects could be reversed with the application of anti-psychotic drugs. Moreover, social interaction abnormalities were observed only in Bdr animals from stressed dams but not in wild-type littermates or mutants from non-stressed mothers. These results show for the first time that combining a synaptic mouse point mutant with a controlled prenatal stressor paradigm produces both modified and previously unseen phenotypes, generating new insights into the interactions between genetics and the environment relevant to the study of psychiatric disease.

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Section: Discussionmentioning

confidence: 99%

Interaction between environmental and genetic factors modulates schizophrenic endophenotypes in the Snap-25 mouse mutant blind-drunk

Oliver

Davies

2009

Human Molecular Genetics

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“…This process will probably stop at the beginning of the third postnatal week, when the morphology of Purkinje cells nearly reaches its final state. Interestingly, this is also the stage at which mice begin to show complex motor behaviors, like running (Glynn et al, 2007). From that stage on, mutants that retain multiple climbing fiber innervation during adulthood, show deficient parallel fiber LTD and impaired motor learning (Aiba et al, 1994;Ichise et al, 2000;Hansel et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Homosynaptic Long-Term Synaptic Potentiation of the “Winner” Climbing Fiber Synapse in Developing Purkinje Cells

Bosman

Takechi²,

Hartmann³

et al. 2008

J. Neurosci.

101

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During the developmental formation of neuronal circuits, redundant synapses are eliminated and persisting synapses strengthened. In the immature cerebellum, climbing fiber-Purkinje cell synapses undergo a pronounced synaptic rewiring, from a multiple innervation around birth to a mono-innervation in adults. An early stage of this process consists in the differentiation of initially equally strong synapses into one "large" and several "small" synaptic inputs. By performing whole-cell recordings in Purkinje cells of rat cerebellar slices, we found that the coincident activation of a Purkinje cell and one of its afferent climbing fibers induces homosynaptic long-term synaptic potentiation (LTP). This LTP requires postsynaptic Ca 2ϩ signaling and involves an increase in the single channel conductance of the postsynaptic AMPA receptors. Interestingly, LTP occurs exclusively at large synaptic inputs. It is not observed at small inputs that are eventually eliminated. Thus, we identified a new form of LTP that is expressed uniquely and just for a restricted period of early development in the large climbing fiber inputs. Our results suggest that this LTP mediates the activity-dependent maturation of the "winner" climbing fiber.

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“…Complexin I knockout (Cplx1 −/− ) mice-which develop a severe adult-onset ataxia-show a delay in the onset of crawling and walking as well as reduced locomotor activity even though their early neurodevelopmental reflexes (i.e. surface righting, cliff aversion and negative geotaxis) are normal (Glynn et al, 2007). Transient delays in hindlimb placing and cliff aversion were observed in a mouse model (Mecp2 1lox ) for Rett syndrome (Picker et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Abnormal motor phenotype in the SMNΔ7 mouse model of spinal muscular atrophy

Butchbach

Edwards

Burghes

2007

Neurobiology of Disease

123

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Spinal muscular atrophy (SMA) is recessive motor neuron disease that affects motor neurons in the anterior horn of the spinal cord. SMA results from the reduction of SMN (survival motor neuron) protein. Even though SMN is ubiquitously expressed, motor neurons are more sensitive to the reduction in SMN than other cell types. We have previously generated mouse models of SMA with varying degrees of clinical severity. So as to more clearly understand the pathogenesis of motor neuron degeneration in SMA, we have characterized the phenotype of the SMNΔ7 SMA mouse which normally lives for 13.6 ± 0.7 days. These mice are smaller than their non-SMA littermates and begin to lose body mass at 10.4 ± 0.4 days. SMNΔ7 SMA mice exhibit impaired responses to surface righting, negative geotaxis and cliff aversion but not to tactile stimulation. Spontaneous motor activity and grip strength are also significantly impaired in SMNΔ7 SMA mice. In summary, we have demonstrated an impairment of neonatal motor responses in SMNΔ7 SMA mice. This phenotype characterization could be used to assess the effectiveness of potential therapies for SMA.

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Early motor development is abnormal in complexin 1 knockout mice

Cited by 35 publications

References 56 publications

Interaction between environmental and genetic factors modulates schizophrenic endophenotypes in the Snap-25 mouse mutant blind-drunk

Interaction between environmental and genetic factors modulates schizophrenic endophenotypes in the Snap-25 mouse mutant blind-drunk

Homosynaptic Long-Term Synaptic Potentiation of the “Winner” Climbing Fiber Synapse in Developing Purkinje Cells

Abnormal motor phenotype in the SMNΔ7 mouse model of spinal muscular atrophy

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