Neurophysiological and Behavioral Effects of Anti-Orexinergic Treatments in a Mouse Model of Huntington's Disease.

Huntington's disease (HD) is associated with sleep and circadian disturbances in addition to hallmark motor and cognitive impairments. Electrophysiological studies on HD mouse models have revealed an aberrant oscillatory activity at the beta frequency, during sleep, that is associated with HD pathology. Moreover, HD animal models display an abnormal sleep-wake cycle and sleep fragmentation.

Altered hippocampal information coding and network synchrony in APP-PS1 mice.

β-amyloid is hypothesized to harm neural function and cognitive abilities by perturbing synaptic transmission and plasticity in Alzheimer's disease (AD). To assess the impact of this pathology on hippocampal neurons' ability to encode flexibly environmental information across learning, we performed electrophysiological recordings of CA1 hippocampal unit activity in AD transgenic mice as they acquired an action-reward association in a spatially defined environment; the behavioral task enabled the precise timing of discrete and intentional behaviors of the animal. We found that the proportion of behavioral task-sensitive cells in wild-type (WT) mice typically increased, whereas the proportion of place cells decreased with learning.

Sleep Physiology Alterations Precede Plethoric Phenotypic Changes in R6/1 Huntington's Disease Mice.

In hereditary neurodegenerative Huntington's disease (HD), there exists a growing consideration that sleep and circadian dysregulations may be important symptoms. It is not known, however, whether sleep abnormalities contribute to other behavioral deficits in HD patients and mouse models. To determine the precise chronology for sleep physiology alterations and other sensory, motor, psychiatric and cognitive symptoms of HD, the same R6/1 HD transgenics and their wild-type littermates were recorded monthly for sleep electroencephalogram (EEG) together with a wide range of behavioral tests according to a longitudinal plan.

β oscillation during slow wave sleep and rapid eye movement sleep in the electroencephalogram of a transgenic mouse model of Huntington's disease.

Study Objectives: To search for early abnormalities in electroencephalogram (EEG) during sleep which may precede motor symptoms in a transgenic mouse model of hereditary neurodegenerative Huntington's disease (HD).

Design: In the R6/1 transgenic mouse model of HD, rhythmic brain activity in EEG recordings was monitored longitudinally and across vigilance states through the onset and progression of disease.

Measurements And Results: Mice with chronic electrode implants were recorded monthly over wake-sleep cycles (4 hours), beginning at 9-11 weeks (presymptomatic period) through 6-7 months (symptomatic period).

Evolution of hippocampal spatial representation over time in mice.

To investigate the intriguing and paradoxical contrast between the time-limited role of the hippocampus in memory consolidation and its permanent contribution to spatial memory as revealed by place cell activity, we carefully monitored the temporal evolution of the same set of place cells in normal naïve mice throughout their familiarization to a spatial context and their consolidation of memory about space. Over six daily recording sessions, despite their widely reported stability, we observed gradual changes in hippocampal place fields and cell firing patterns. These changes were interpreted in terms of both improvement and impoverishment of spatial codes: improvement due to intrinsic place cell plasticity, and impoverishment as a consequence of attentional filtering of allocentric spatial information reaching the hippocampus due to the procedural behavioral requirements of the task, or to hippocampal disengagement as learning progresses.