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The amyloid-β (Aβ) oligomer is considered one of the major pathogens responsible for neuronal and synaptic loss in Alzheimer's disease (AD) brains. Although the neurotoxic mechanisms of Aβ have been widely investigated, experimental evidence for the direct linkage between neural signaling and cognitive impairments in association with peptide oligomers is lacking. Here, we conducted an auditory oddball paradigm utilizing an Aβ-infused Alzheimer's disease mouse model and interpreted the results based on Y-maze behavioral tests. We acutely injected Aβ oligomers into the intracerebroventricular brain region of normal mice to induce Aβ-associated cognitive impairments. During the auditory oddball paradigm, electroencephalograms (EEG) were recorded from frontal and parietal cortex of Aβ-infused and control mice. The event-related potentials (ERPs) elicited by auditory stimuli showed no significant difference in Aβ-infused mice compared to control mice. On the other hand, the differential ERP signature elicited by oddball sound stimuli was destructed in the Aβ-infused mice group. We noticed that ERP traces to standard and deviant tones were not significantly different in the Aβ group, while the control group showed differences in the amplitude of ERP components. In particular, the difference in the first negative component (N1) between standard and deviant tone, which indexes the sensory memory system, was significantly reduced in the parietal cortex of Aβ-infused mice. These findings demonstrate the direct influence of Aβ oligomers on the functional integrity of cortical areas in vivo. Furthermore, the N1 amplitude difference may provide a potential marker of sensory memory deficits in a mouse model of AD and yield additional targets for drug assessment in AD. [ABSTRACT FROM AUTHOR]

The mouse model is an important research tool in neurosciences to examine brain function and diseases with genetic perturbation in different brain regions. However, the limited techniques to map activated brain regions under specific experimental manipulations has been a drawback of the mouse model compared to human functional brain mapping. Here, we present a functional brain mapping method for fast and robust in vivo brain mapping of the mouse brain. The method is based on the acquisition of high density electroencephalography (EEG) with a microarray and EEG source estimation to localize the electrophysiological origins. We adapted the Fieldtrip toolbox for the source estimation, taking advantage of its software openness and flexibility in modeling the EEG volume conduction. Three source estimation techniques were compared: Distribution source modeling with minimum-norm estimation (MNE), scanning with multiple signal classification (MUSIC), and single-dipole fitting. Known sources to evaluate the performance of the localization methods were provided using optogenetic tools. The accuracy was quantified based on the receiver operating characteristic (ROC) analysis. The mean detection accuracy was high, with a false positive rate less than 1.3% and 7% at the sensitivity of 90% plotted with the MNE and MUSIC algorithms, respectively. The mean center-to-center distance was less than 1.2 mm in single dipole fitting algorithm. Mouse microarray EEG source localization using microarray allows a reliable method for functional brain mapping in awake mouse opening an access to cross-species study with human brain. [ABSTRACT FROM AUTHOR]

The thalamocortical system plays a key role in the breakdown or emergence of consciousness, providing bottom-up information delivery from sensory afferents and integrating top-down intracortical and thalamocortical reciprocal signaling. A fundamental and so far unanswered question for cognitive neuroscience remains whether the thalamocortical switch for consciousness works in a discontinuous manner or not. To unveil the nature of thalamocortical system phase transition in conjunction with consciousness transition, ketamine/xylazine was administered unobtrusively to ten mice under a forced working test with motion tracker, and field potentials in the sensory and motor-related cortex and thalamic nuclei were concomitantly collected. Sensory and motor-related thalamocortical networks were found to behave continuously at anesthesia induction and emergence, as evidenced by a sigmoidal response function with respect to anesthetic concentration. Hyperpolarizing and depolarizing susceptibility diverged, and a non-discrete change of transitional probability occurred at transitional regimes, which are hallmarks of continuous phase transition. The hyperpolarization curve as a function of anesthetic concentration demonstrated a hysteresis loop, with a significantly higher anesthetic level for transition to the down state compared to transition to the up state. Together, our findings concerning the nature of phase transition in the thalamocortical system during consciousness transition further elucidate the underlying basis for the ambiguous borderlines between conscious and unconscious brains. Moreover, our novel analysis method can be applied to systematic and quantitative handling of subjective concepts in cognitive neuroscience.