The pros and cons of using automated sleep scoring in sleep research.

Sleep scoring plays a pivotal role both in sleep research and in clinical practice. Traditionally, this process has relied on manual scoring by human experts, but it is marred by time constraints, and inconsistencies between different scorers. Consequently, the quest for more efficient and reliable approaches has sparked a great interest in the realm of automatic sleep-scoring methods. In this article, we provide an exploration of the merits and drawbacks of automatic sleep scoring, alongside the pressing challenges and critical considerations that demand attention in this evolving field.

CBD lengthens sleep but shortens ripples and leads to intact simple but worse cumulative memory.

Cannabidiol (CBD) is on the rise as over-the-counter medication to treat sleep disturbances, anxiety, pain, and epilepsy due to its action on the excitatory/inhibitory balance in the brain. However, it remains unclear if CBD also leads to adverse effects on memory via changes of sleep macro- and microarchitecture. To investigate the effect of CBD on sleep and memory consolidation, we performed two experiments using the object space task testing for both simple and cumulative memory in rats. We show that oral CBD administration extended the sleep period but changed the properties of rest and non-REM sleep oscillations (delta, spindle, ripples). Specifically, CBD also led to less long (>100 ms) ripples and, consequently, worse cumulative memory consolidation. In contrast, simple memories were not affected. In sum, we can confirm the beneficial effect of CBD on sleep; however, this comes with changes in oscillations that negatively impact memory consolidation.

Increased cortical plasticity leads to memory interference and enhanced hippocampal-cortical interactions.

Our brain is continuously challenged by daily experiences. Thus, how to avoid systematic erasing of previously encoded memories? While it has been proposed that a dual-learning system with 'slow' learning in the cortex and 'fast' learning in the hippocampus could protect previous knowledge from interference, this has never been observed in the living organism. Here, we report that increasing plasticity via the viral-induced overexpression of RGS14414 in the prelimbic cortex leads to better one-trial memory, but that this comes at the price of increased interference in semantic-like memory. Indeed, electrophysiological recordings showed that this manipulation also resulted in shorter NonREM-sleep bouts, smaller delta-waves and decreased neuronal firing rates. In contrast, hippocampal-cortical interactions in form of theta coherence during wake and REM-sleep as well as oscillatory coupling during NonREM-sleep were enhanced. Thus, we provide the first experimental evidence for the long-standing and unproven fundamental idea that high thresholds for plasticity in the cortex protect preexisting memories and modulating these thresholds affects both memory encoding and consolidation mechanisms.

Sleep scoring in rodents: Criteria, automatic approaches and outstanding issues.

There is nothing we spend as much time on in our lives as we do sleeping, which makes it even more surprising that we currently do not know why we need to sleep. Most of the research addressing this question is performed in rodents to allow for invasive, mechanistic approaches. However, in contrast to human sleep, we currently do not have shared and agreed upon standards on sleep states in rodents. In this article, we present an overview on sleep stages in humans and rodents and a historical perspective on the development of automatic sleep scoring systems in rodents. Further, we highlight specific issues in rodent sleep that also call into question some of the standards used in human sleep research.

Learning shifts the preferred theta phase of gamma oscillations in CA1.

Hippocampal neuronal oscillations reflect different cognitive processes and can therefore be used to dissect the role of hippocampal subfields in learning and memory. In particular, it has been suggested that encoding and retrieval is associated with slow gamma (25-55 Hz) and fast gamma (60-100 Hz) oscillations, respectively, which appear in a nested manner at specific phases of the ongoing theta oscillations (4-12 Hz). However, the relationship between memory demand and the theta phase of gamma oscillations remains unclear. Here, we assessed the theta phase preference of gamma oscillations in the CA1 region, at the starting and junction zones of a T-maze, while rats were learning an appetitive task. We found that the theta phase preference of slow gamma showed a ~180° phase shift when animals switched from novice to skilled performance during task acquisition. This phase-shift was not present at the junction zone, where animals chose a right or left turn within the T-maze, suggesting that a recall/decision process had already taken place at the starting zone. Our findings indicate that slow gamma oscillations support both encoding and retrieval, depending on the theta phase at which they occur. These properties are particularly evident prior to cognitive engagement in an acquired spatial task.

Experience-Dependency of Reliance on Local Visual and Idiothetic Cues for Spatial Representations Created in the Absence of Distal Information.

Spatial encoding in the hippocampus is based on a range of different input sources. To generate spatial representations, reliable sensory cues from the external environment are integrated with idiothetic cues, derived from self-movement, that enable path integration and directional perception. In this study, we examined to what extent idiothetic cues significantly contribute to spatial representations and navigation: we recorded place cells while rodents navigated towards two visually identical chambers in 180° orientation via two different paths in darkness and in the absence of reliable auditory or olfactory cues. Our goal was to generate a conflict between local visual and direction-specific information, and then to assess which strategy was prioritized in different learning phases. We observed that, in the absence of distal cues, place fields are initially controlled by local visual cues that override idiothetic cues, but that with multiple exposures to the paradigm, spaced at intervals of days, idiothetic cues become increasingly implemented in generating an accurate spatial representation. Taken together, these data support that, in the absence of distal cues, local visual cues are prioritized in the generation of context-specific spatial representations through place cells, whereby idiothetic cues are deemed unreliable. With cumulative exposures to the environments, the animal learns to attend to subtle idiothetic cues to resolve the conflict between visual and direction-specific information.

Activity-dependent switch of GABAergic inhibition into glutamatergic excitation in astrocyte-neuron networks.

Interneurons are critical for proper neural network function and can activate Ca2+ signaling in astrocytes. However, the impact of the interneuron-astrocyte signaling into neuronal network operation remains unknown. Using the simplest hippocampal Astrocyte-Neuron network, i.e., GABAergic interneuron, pyramidal neuron, single CA3-CA1 glutamatergic synapse, and astrocytes, we found that interneuron-astrocyte signaling dynamically affected excitatory neurotransmission in an activity- and time-dependent manner, and determined the sign (inhibition vs potentiation) of the GABA-mediated effects. While synaptic inhibition was mediated by GABAA receptors, potentiation involved astrocyte GABAB receptors, astrocytic glutamate release, and presynaptic metabotropic glutamate receptors. Using conditional astrocyte-specific GABAB receptor (Gabbr1) knockout mice, we confirmed the glial source of the interneuron-induced potentiation, and demonstrated the involvement of astrocytes in hippocampal theta and gamma oscillations in vivo. Therefore, astrocytes decode interneuron activity and transform inhibitory into excitatory signals, contributing to the emergence of novel network properties resulting from the interneuron-astrocyte interplay.