Abstract
All individuals with Down syndrome (DS) have a varying but significant degree of cognitive disability. Although hippocampal deficits clearly play an important role, behavioral studies also suggest that deficits within the neocortex contribute to somatosensory deficits and impaired cognition in DS. Using thalamocortical slices from the Ts65Dn mouse model of DS, we investigated the intrinsic and network properties of regular spiking neurons within layer 4 of the somatosensory cortex. In these neurons, the membrane capacitance was increased and specific membrane resistance decreased in slices from Ts65Dn mice. Examination of combined active and passive membrane properties suggests that trisomic layer 4 neurons are less excitable than those from euploid mice. The frequencies of excitatory and inhibitory spontaneous synaptic activities were also reduced in Ts65Dn neurons. With respect to network activity, spontaneous network oscillations (Up states) were shorter and less numerous in the neocortex from Ts65Dn mice when compared to euploid. Up states evoked by electrical stimulation of the ventrobasal nucleus (VBN) of the thalamus were similarly affected in Ts65Dn mice. Additionally, monosynaptic EPSCs and polysynaptic IPSCs evoked by VBN stimulation were significantly delayed in layer 4 regular spiking neurons from Ts65Dn mice. These results indicate that, in the Ts65Dn model of DS, the overall electrophysiological properties of neocortical neurons are altered leading to aberrant network activity within the neocortex. Similar changes in DS individuals may contribute to sensory and cognitive dysfunction and therefore may implicate new targets for cognitive therapies in this developmental disorder.
Highlights
Down syndrome (DS), which results from triplication of genes on human chromosome 21 (Hsa21) is associated with significant cognitive deficits mainly in spatial cognition mediated by the hippocampus (Chapman and Hesketh 2000; Pennington et al 2003; Edgin et al 2010; Haydar and Reeves 2012)
Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society
We examined whether intrinsic properties of regular spiking (RS) neurons in the somatosensory cortex of trisomic Ts65Dn mice were altered when compared with their littermates
Summary
Down syndrome (DS), which results from triplication of genes on human chromosome 21 (Hsa21) is associated with significant cognitive deficits mainly in spatial cognition mediated by the hippocampus (Chapman and Hesketh 2000; Pennington et al 2003; Edgin et al 2010; Haydar and Reeves 2012). Morphological and functional abnormalities throughout the nervous system but within the hippocampus have been implicated as contributing factors to diminished cognitive capabilities in DS individuals (Sylvester 1983; Ferrer and Gullotta 1990; Pinter et al 2001; Smigielska-Kuzia et al 2011). The neocortex contributes significantly to cognition at many levels including working memory Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
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