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Abstract Introduction The Ts65Dn mouse is the most widely used animal model of Down syndrome (DS). Differences in autonomic regulation of heart rate variability (HRV) in individuals with DS have been hypothesized. Pharmacological studies in animal models may help us understand mechanisms underlying observed changes in HRV in people with DS. Objective To investigate the use a new, noninvasive technique to assess cardiac autonomic modulation in Ts65Dn mice under the effect of adrenergic and cholinergic agonists. Method We recorded electrocardiograms (ECGs) from 12 Ts65Dn and 12 euploid control mice. A 30‐min baseline recording was followed by the injection of an adrenergic (isoproterenol [Iso]) or cholinergic (carbachol [CCh]) agonist. Heart rate and HRV were analyzed using a series of methods customized for mice. Results and Discussion The ECG apparatus described here allowed us to detect noninvasively long series of heartbeats in freely‐moving animals. During baseline conditions, the yield of detectable heartbeats was 3%–27% of the estimated total number of events, which increased to 35%–70% during the 15‐min period after either Iso or CCh injections. Ts65Dn mice displayed a robust enhanced Iso‐induced negative chronotropic rebound response compared with euploid control mice. We observed a significantly smaller CCh response in Ts65Dn versus control euploid mice in the 6‐ to 10‐min‐interval postcarbachol injection. Conclusion This work showed that the techniques described here are sufficient for this type of study. However, future studies involving the use of more selective pharmacological agents and/or genetic manipulations will be key to advance a mechanistic understanding of cardiac autonomic regulation in DS.

Introduction: The Ts65Dn mouse is the most widely used animal model of Down syndrome (DS). Differences in autonomic regulation of heart rate variability (HRV) in individuals with DS have been hypothesized. Pharmacological studies in animal models may help us understand mechanisms underlying observed changes in HRV in people with DS. Objective: To investigate the use a new, noninvasive technique to assess cardiac autonomic modulation in Ts65Dn mice under the effect of adrenergic and cholinergic agonists. Method: We recorded electrocardiograms (ECGs) from 12 Ts65Dn and 12 euploid control mice. A 30‐min baseline recording was followed by the injection of an adrenergic (isoproterenol [Iso]) or cholinergic (carbachol [CCh]) agonist. Heart rate and HRV were analyzed using a series of methods customized for mice. Results and Discussion: The ECG apparatus described here allowed us to detect noninvasively long series of heartbeats in freely‐moving animals. During baseline conditions, the yield of detectable heartbeats was 3%–27% of the estimated total number of events, which increased to 35%–70% during the 15‐min period after either Iso or CCh injections. Ts65Dn mice displayed a robust enhanced Iso‐induced negative chronotropic rebound response compared with euploid control mice. We observed a significantly smaller CCh response in Ts65Dn versus control euploid mice in the 6‐ to 10‐min‐interval postcarbachol injection. Conclusion: This work showed that the techniques described here are sufficient for this type of study. However, future studies involving the use of more selective pharmacological agents and/or genetic manipulations will be key to advance a mechanistic understanding of cardiac autonomic regulation in DS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]