52 research outputs found
Preservation of long-term memory and synaptic plasticity despite short-term impairments in the Tc1 mouse model of Down syndrome
Down syndrome (DS) is a genetic disorder arising from the presence of a third copy of the human chromosome 21 (Hsa21). Recently, O’Doherty and colleagues in an earlier study generated a new genetic mouse model of DS (Tc1) that carries an almost complete Hsa21. Since DS is the most common genetic cause of mental retardation, we have undertaken a detailed analysis of cognitive function and synaptic plasticity in Tc1 mice. Here we show that Tc1 mice have impaired spatial working memory (WM) but spared long-term spatial reference memory (RM) in the Morris watermaze. Similarly, Tc1 mice are selectively impaired in short-term memory (STM) but have intact long-term memory (LTM) in the novel object recognition task. The pattern of impaired STM and normal LTM is paralleled by a corresponding phenotype in long-term potentiation (LTP). Freely-moving Tc1 mice exhibit reduced LTP 1 h after induction but normal maintenance over days in the dentate gyrus of the hippocampal formation. Biochemical analysis revealed a reduction in membrane surface expression of the AMPAR (α-amino-3-hydroxy-5-methyl-4-propionic acid receptor) subunit GluR1 in the hippocampus of Tc1 mice, suggesting a potential mechanism for the impairment in early LTP. Our observations also provide further evidence that STM and LTM for hippocampus-dependent tasks are subserved by parallel processing streams
Impairments in motor coordination without major changes in cerebellar plasticity in the Tc1 mouse model of Down syndrome
Down syndrome (DS) is a genetic disorder arising from the presence of a third copy of human chromosome
21 (Hsa21). Recently, O’Doherty et al. [An aneuploid mouse strain carrying human chromosome 21 with Down
syndrome phenotypes. Science 309 (2005) 2033–2037] generated a trans-species aneuploid mouse line (Tc1)
that carries an almost complete Hsa21. The Tc1 mouse is the most complete animal model for DS currently
available. Tc1 mice show many features that relate to human DS, including alterations in memory, synaptic
plasticity, cerebellar neuronal number, heart development and mandible size. Because motor deficits are
one of the most frequently occurring features of DS, we have undertaken a detailed analysis of motor behaviour
in cerebellum-dependent learning tasks that require high motor coordination and balance. In addition,
basic electrophysiological properties of cerebellar circuitry and synaptic plasticity have been investigated.
Our results reveal that, compared with controls, Tc1 mice exhibit a higher spontaneous locomotor activity,
a reduced ability to habituate to their environments, a different gait and major deficits on several measures
of motor coordination and balance in the rota rod and static rod tests. Moreover, cerebellar long-term
depression is essentially normal in Tc1 mice, with only a slight difference in time course. Our observations
provide further evidence that support the validity of the Tc1 mouse as a model for DS, which will help us to
provide insights into the causal factors responsible for motor deficits observed in persons with DS
Dynamical model of sequential spatial memory: winnerless competition of patterns
We introduce a new biologically-motivated model of sequential spatial memory
which is based on the principle of winnerless competition (WLC). We implement
this mechanism in a two-layer neural network structure and present the learning
dynamics which leads to the formation of a WLC network. After learning, the
system is capable of associative retrieval of pre-recorded sequences of spatial
patterns.Comment: 4 pages, submitted to PR
Analysis of the intraspinal calcium dynamics and its implications on the plasticity of spiking neurons
The influx of calcium ions into the dendritic spines through the
N-metyl-D-aspartate (NMDA) channels is believed to be the primary trigger for
various forms of synaptic plasticity. In this paper, the authors calculate
analytically the mean values of the calcium transients elicited by a spiking
neuron undergoing a simple model of ionic currents and back-propagating action
potentials. The relative variability of these transients, due to the stochastic
nature of synaptic transmission, is further considered using a simple Markov
model of NMDA receptos. One finds that both the mean value and the variability
depend on the timing between pre- and postsynaptic action-potentials. These
results could have implications on the expected form of synaptic-plasticity
curve and can form a basis for a unified theory of spike time-dependent, and
rate based plasticity.Comment: 14 pages, 10 figures. A few changes in section IV and addition of a
new figur
Ntab, a novel non-coding RNA abundantly expressed in rat brain
We have identified a novel transcript that is abundantly and specifically expressed in both the adult and developing rat CNS. Within the full-length cDNA sequence we were unable to identify a clear open reading frame. Moreover, we were unable to detect any protein product derived from the full-length cDNA sequence using an in vitro translation assay. Therefore, we suggest this gene is one of a growing number of non-coding mRNA-like RNA transcripts that exert their cellular functions directly as an RNA. We have named this novel gene Ntab for non-coding transcript abundantly expressed in brain (accession number AY035551). In addition, in some regions of the brain we find evidence for RNA accumulation in cellular processes at some distance from the soma. These findings suggest that Ntab is actively transported and may function within cellular processes. Since Ntab is a targeted non-coding RNA, such cellular functions could include the targeting and/or regulation of localised translation of other mRNA species
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