Substance specific EEG patterns in mice undergoing slow anesthesia induction.

The exact mechanisms and the neural circuits involved in anesthesia induced unconsciousness are still not fully understood. To elucidate them valid animal models are necessary. Since the most commonly used species in neuroscience are mice, we established a murine model for commonly used anesthetics/sedatives and evaluated the epidural electroencephalographic (EEG) patterns during slow anesthesia induction and emergence. Forty-four mice underwent surgery in which we inserted a central venous catheter and implanted nine intracranial electrodes above the prefrontal, motor, sensory, and visual cortex. After at least one week of recovery, mice were anesthetized either by inhalational sevoflurane or intravenous propofol, ketamine, or dexmedetomidine. We evaluated the loss and return of righting reflex (LORR/RORR) and recorded the electrocorticogram. For spectral analysis we focused on the prefrontal and visual cortex. In addition to analyzing the power spectral density at specific time points we evaluated the changes in the spectral power distribution longitudinally. The median time to LORR after start anesthesia ranged from 1080 [1st quartile: 960; 3rd quartile: 1080]s under sevoflurane anesthesia to 1541 [1455; 1890]s with ketamine. Around LORR sevoflurane as well as propofol induced a decrease in the theta/alpha band and an increase in the beta/gamma band. Dexmedetomidine infusion resulted in a shift towards lower frequencies with an increase in the delta range. Ketamine induced stronger activity in the higher frequencies. Our results showed substance-specific changes in EEG patterns during slow anesthesia induction. These patterns were partially identical to previous observations in humans, but also included significant differences, especially in the low frequencies. Our study emphasizes strengths and limitations of murine models in neuroscience and provides an important basis for future studies investigating complex neurophysiological mechanisms.

Altered sleep behavior strengthens face validity in the ArcAß mouse model for Alzheimer's disease.

Demographic changes will expand the number of senior citizens suffering from Alzheimer's disease (AD). Key aspects of AD pathology are sleep impairments, associated with onset and progression of AD. AD mouse models may provide insights into mechanisms of AD-related sleep impairments. Such models may also help to establish new biomarkers predicting AD onset and monitoring AD progression. The present study aimed to establish sleep-related face validity of a widely used mouse model of AD (ArcAß model) by comprehensively characterizing its baseline sleep/wake behavior. Chronic EEG recordings were performed continuously on four consecutive days in freely behaving mice. Spectral and temporal sleep/wake parameters were assessed and analyzed. EEG recordings showed decreased non-rapid eye movement sleep (NREMS) and increased wakefulness in transgenic mice (TG). Vigilance state transitions were different in TG mice when compared to wildtype littermates (WT). During NREMS, TG mice had lower power between 1 and 5 Hz and increased power between 5 and 30 Hz. Sleep spindle amplitudes in TG mice were lower. Our study strongly provides sleep-linked face validity for the ArcAß model. These findings extend the potential of the mouse model to investigate mechanisms of AD-related sleep impairments and the impact of sleep impairments on the development of AD.

Altered sleep behavior in a genetic mouse model of impaired fear extinction.

Sleep disturbances are a common complaint of anxiety patients and constitute a hallmark feature of post-traumatic stress disorder (PTSD). Emerging evidence suggests that poor sleep is not only a secondary symptom of anxiety- and trauma-related disorders but represents a risk factor in their development, for example by interfering with emotional memory processing. Fear extinction is a critical mechanism for the attenuation of fearful and traumatic memories and multiple studies suggest that healthy sleep is crucial for the formation of extinction memories. However, fear extinction is often impaired in anxiety- and trauma-related disorders-an endophenotype that is perfectly modelled in the 129S1/SvImJ inbred mouse strain. To investigate whether these mice exhibit altered sleep at baseline that could predispose them towards maladaptive fear processing, we compared their circadian sleep/wake patterns to those of typically extinction-competent C57BL/6 mice. We found significant differences regarding diurnal distribution of sleep and wakefulness, but also sleep architecture, spectral features and sleep spindle events. With regard to sleep disturbances reported by anxiety- and PTSD patients, our findings strengthen the 129S1/SvImJ mouse models' face validity and highlight it as a platform to investigate novel, sleep-focused diagnostic and therapeutic strategies. Whether the identified alterations causally contribute to its pathological anxiety/PTSD-like phenotype will, however, have to be addressed in future studies.

Combined implanted central venous access and cortical recording electrode array in freely behaving mice.

Establishing a long-lasting, functioning venous access in a non-anesthetized mouse is very challenging at least. Since we needed a reliable venous access to titrate intravenous anesthetics, we refined and combined previously described methods. The tunneling of the catheter from the cranial to the pectoral wound, the fixation of the catheter in the external jugular vein with two sutures, and a tissue adhesive allowed us to combine this method with the implantation of intracranial recording electrodes. With this approach we neither have to restrain the animal causing excessive stress nor do we need an additional anesthetic, interfering with the effects of the intravenous anesthetic. This approach can help to establish a greater understanding of the concept of consciousness by identifying the neural circuits which mediate the effect of intravenous anesthetics. In addition - due to the flexible design of the recording electrode array - our approach can also be applied to investigate further neuroscientific hypotheses.•Establishment of a reliable chronical venous access for the application in freely behaving mice.•The jugular venous access can be combined with all kinds of neurobiological recording and application designs.•The design of the venous access allows chronic combinations with telemetric and tether-bound systems.