Biology subjects

Genzel, L.

Publications and source records attributed to Genzel, L..

15 recordsLinked to original sources

bioRxiv2025

Uncovering Sleep's Hippocampal-Cortical Dialogue: The Role of Deltas' and Spindles' Cross-Area Synchronization and Ripple Subtypes

Hippocampal ripples, critical for sleep-related memory consolidation, are heterogeneous events with various sources and functions. Here we applied principal component analysis to identify ripple sub-types and relate them to hippocampal-cortical interactions as well as their role in consolidating simple and complex semantic-like memories in rats. Three main ripple types were discovered: baseline, large-input, and small-input ripples. Small-input ripples, were associated with increased prefrontal cortex to hippocampus connectivity, followed hippocampal delta waves, and were sufficient for simple learning. In contrast, large-input ripples exhibited increased hippocampus to prefrontal cortex connectivity, occurred during hippocampal spindles together as a doublet with a small-input ripple, and were critical for complex memory consolidation. Finally, learning induced heightened coupling between hippocampal delta and spindle oscillations and their cortical counterparts, consequently leading to an increased synchronization of ripples with cortical oscillations. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/644132v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@b94b1borg.highwire.dtl.DTLVardef@f1fff0org.highwire.dtl.DTLVardef@1da0c00org.highwire.dtl.DTLVardef@4a0008_HPS_FORMAT_FIGEXP M_FIG C_FIG Significance StatementThis pioneering, data-driven approach is the first to connect distinct ripple sub-types to precise cross- brain computational states, revealing their role in consolidating various types of memories.

neuroscience↗

bioRxiv2024

Differential Contributions of CA3 and Entorhinal Cortex Inputs to Ripple Patterns in the Hippocampus Under Cannabidiol

Cannabidiol (CBD), increasingly recognized for its potential to treat insomnia, notably extends NonREM sleep phases and modifies sleep-associated ripple dynamics. Utilizing a threshold-based approach, our study differentiated distinct ripple types in rats, clarifying the contributions of intra-hippocampal (CA3) and cortical (mEC) regions to these events. The findings reveal that CBD primarily influences the CA3s input to the CA1, resulting in an increased occurrence of short ripples predominantly induced by cortical (mEC) activity and a corresponding decrease in long, intra-hippocampal sharp-wave-ripples. This study highlights the critical interplay between the CA3 and entorhinal cortex dynamics in shaping the characteristics of hippocampal ripples under the influence of CBD.

neuroscience↗

bioRxiv2024

The TD drive - A parametric, open-source implant for multi-area electrophysiological recordings in behaving and sleeping rats

Intricate interactions between multiple brain areas underlie most functions attributed to the brain. The process of learning, as well as formation and consolidation of memories are two examples that rely heavily on functional connectivity across the brain. In addition, investigating hemispheric similarities and/or differences goes hand in hand with these multi-area interactions. Electrophysiological studies trying to further elucidate these complex processes thus depend on recording brain activity at multiple locations simultaneously and often in a bilateral fashion. Presented here is a 3D-printable implant for rats, named TD drive, capable of symmetric, bilateral wire electrode recordings, currently in up to ten distributed brain areas simultaneously. The open-source design was created employing parametric design principles, allowing prospective users to easily adapt the drive design to their needs by simply adjusting high-level parameters, such as anterior-posterior and medio-lateral coordinates of the recording electrode locations. The implant design was validated in n = 20 Lister Hooded rats that performed different tasks. The implant was compatible with tethered sleep recordings and open field recordings (Object Exploration) as well as wireless recording in a large maze (HexMaze 9x5 m) using two different commercial recording systems and headstages. In sum, presented here is the adaptable design and assembly of a new electrophysiological implant facilitating fast preparation and implantation.

neuroscience↗

bioRxiv2023

CBD lengthens sleep, 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 via changes of sleep macro- and microarchitecture. To investigate the effect of CBD on sleep and sleep-related memory consolidation, we performed two experiments using the Object Space Task testing both simple and cumulative memory in rats. We show that oral CBD administration extended the sleep period but changed the properties of NonREM sleep oscillations (delta, spindle, ripples). Specifically, CBD also led to less long (>100ms) 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 NonREM oscillations that negatively impact memory consolidation.

neuroscience↗

bioRxiv2022

Learning Fast and Slow: 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 protects preexisting memories and modulating these thresholds affects both memory encoding and consolidation mechanisms.

neuroscience↗

bioRxiv2022

Defensive and offensive behaviors in social interaction settings in a Kleefstra syndrome mouse model

Kleefstra syndrome in humans is characterized by general delay in development, intellectual disability and autistic features. The mouse model of this disease (Ehmt1+/-) expresses anxiety, autistic-like traits, and aberrant social interactions with non-cagemates. To investigate how Ehmt1+/- mice behave with unfamiliar conspecifics, we allowed adult, male animals to freely interact for 10 minutes in a neutral, novel environment within a host-visitor setting. In 17 out of 74 trials there were defensive and offensive behaviors. Our key finding was that Ehmt1+/- mice displayed defensive postures, attacking and biting; in contrast, wild-type (WT) interacting with other WT did not enact such behaviors. Further, if there was a fight between an Ehmt1+/- and a WT mouse, it was always the Ehmt1+/- who initiated these behaviors.

neuroscience↗

bioRxiv2021

Spindle - slow oscillation coupling correlates with memory performance and connectivity changes in a hippocampal network after sleep

After experiences are encoded, post-encoding reactivations during sleep have been proposed to mediate long-term memory consolidation. Spindle-slow oscillation coupling during NREM sleep is a candidate mechanism through which a hippocampal-cortical dialogue may strengthen a newly formed memory engram. Here, we investigated the role of fast spindle- and slow spindle-slow oscillation coupling in the consolidation of spatial memory in humans with a virtual water maze task involving allocentric and egocentric learning strategies. Furthermore, we analyzed how resting-state functional connectivity evolved across learning, consolidation, and retrieval of this task using a data-driven approach. Our results show task-related connectivity changes in the executive control network, the default mode network, and the hippocampal network at post-task rest. The hippocampal network could further be divided into two subnetworks of which only one showed modulation by sleep. Decreased functional connectivity in this subnetwork was associated with higher spindle-slow oscillation coupling power, which was also related to better memory performance at test. Overall, this study contributes to a more holistic understanding of the functional resting-state networks and the mechanisms during sleep associated to spatial memory consolidation.

neuroscience↗

bioRxiv2021

Circadian modulation of human sleep spindle frequency

Homeostatic and circadian processes play a pivotal role in determining sleep structure, timing and quality. In sharp contrast with the wide accessibility of the EEG index of sleep homeostasis, an electrophysological measure of the circadian modulation of sleep is still non-available. Evidence suggests that sleep spindle frequencies decelerate during biological night. In order to test the feasibility of measuring this marker in common polysomnographic protocols, the Budapest-Munich database of sleep records (N = 251 healthy subjects, 122 females, age range: 4-69 years), as well as an afternoon nap sleep record database (N = 112 healthy subjects, 30 females, age range: 18-30 years) were analysed by the Individual Adjustment Method of sleep spindle analysis. Slow and fast sleep spindle frequencies were characterized by U-shaped overnight dynamics, with highest values in the first and the fourth-to-fifth sleep cycle and the lowest values in the middle of the sleeping period (cycles 2-3). Age-related attenuation of sleep spindle deceleration was evident. Estimated phases of the nadirs in sleep spindle frequencies were advanced in children as compared to other age groups. Additionally, nap sleep spindles were faster than night sleep spindles (0.57 and 0.39 Hz difference for slow and fast types, respectively). The fine frequency resolution analysis of sleep spindles is a feasible method of measuring the assumed circadian modulation of sleep. Moreover, age-related attenuation of circadian sleep modulation might be measurable by assessing the overnight dynamics in sleep spindle frequency. Phase of the minimal sleep spindle frequency is a putative biomarker of chronotype.

neuroscience↗

bioRxiv2020

Schema-induced shifts in mice navigational strategies are unveiled by a minimal behavioral model of spatial exploration.

Shifts in spatial patterns produced during the execution of a navigational task can be used to track the effects of the accumulation of knowledge and the acquisition of structured information about the environment. Here we provide a quantitative analysis of mice behavior while performing a novel goal localization task in a large, modular arena, the HexMaze. To demonstrate the effects of different forms of previous knowledge we first obtain a precise statistical characterization of animals paths with sub-trial resolution and over different phases of learning. The emergence of a flexible representation of the task is accompanied by a progressive improvement of performance, mediated by multiple, multiplexed time scales. We then use a generative mathematical model of the animal behavior to isolate the specific contributions to the final navigational strategy. We find that animal behavior can be accurately reproduced by the combined effect of a goal-oriented component, becoming stronger with the progression of learning, and of a random walk component, producing choices unrelated to the task and only partially weakened in time.

neuroscience↗

bioRxiv2020

Sleep leads to system-wide neural changes independent of allo- and egocentric spatial training in humans and rats

Sleep is important for memory consolidation, especially the process of systems consolidation should occur during sleep. While a significant amount of research has been done in regards to the effect of sleep on behavior and certain mechanisms during sleep, until now evidence is lacking that sleep leads to consolidation across the system. Here, we investigated the role of sleep in consolidation of spatial memory in the watermaze in both rats and humans using allocentric and egocentric based training. Combining behavior with immediate early gene expression analysis in rodents and functional MR imaging in humans, elucidated similar behavioral and neural effects in both species. Rats and humans showed a benefit of sleep on behavior. Interestingly, sleep led to systems-wide retrieval network in both species in both training conditions. Thus, we provide cross-species evidence for memory consolidation on the system-level occurring during sleep. Significance StatementProcesses occurring during sleep such as memory reactivations are proposed to lead to consolidation from the initial hippocampal memory representation to long-lasting cortical representations, this is known as systems consolidation. By combining behavioral measurements in the watermaze with immediate early gene expression analysis in rats and function magnetic resonance imaging in humans, we could show a benefit of sleep on behavioral memory performance. And, sleep lead to systems-wide changes in the retrieval network. These results are the first direct evidence supporting the role of sleep for systems-wide memory consolidation in both rats and humans.

neuroscience↗

bioRxiv2019

The Object Space Task reveals a dissociation between semantic-like and episodic-like memory in a mouse model of Kleefstra Syndrome

Kleefstra syndrome is a disorder caused by a mutation in the EHMT1 gene characterized in humans by general developmental delay, mild to severe intellectual disability and autism. Here, we characterized semantic- and episodic-like memory in the Ehmt1+/- mouse model using the Object Space Task. We combined conventional behavioral analysis with automated analysis by deep-learning networks, a session-based computational learning model and a trial-based classifier. Ehmt1 +/- mice showed more anxiety-like features and generally explored objects less, but the difference decreased over time. Interestingly, when analyzing memory-specific exploration, Ehmt1 +/- show increased expression of semantic-like memory, but a deficit in episodic-like memory. A similar dissociation of semantic and episodic memory performance has been previously reported in humans with autism. Using our automatic classifier to differentiate between genotypes, we found that semantic-like memory features are better suited for classification than general exploration differences. Thus, detailed behavioral classification with the Object Space Task produced a more detailed behavioral phenotype of the Ehmt1 +/- mouse model.\n\nOne Sentence SummaryEhmt1 +/- mice show decreased exploration and episodic-like memory but increased semantic-like memory In the Object Space Task. (143 of 150)

neuroscience↗

bioRxiv2019

Experience-dependent changes to cortico-hippocampal networks during NREM sleep

Memory reactivation during NonREM-ripples is thought to communicate new information to a systems-wide network. Cortical high frequency events have also been described that co-occur with ripples. Focusing on NonREM sleep after different behaviors, both hippocampal ripples and parietal high frequency oscillations were detected. A bimodal frequency distribution was observed in the parietal high frequency events, faster and slower, with increases in prefrontal directionality measured by Granger causality analysis specifically seen during the fast parietal oscillations. Furthermore, fast events activated prefrontal-parietal cortex whereas slow events activated hippocampal-parietal areas. Finally, there was a learning-induced increase in both number and size of fast high frequency events. These patterns were not seen after novelty exposure or foraging, but occurred after the learning of a new goal location in a maze. Disruption of either sleep or hippocampal ripples impaired long-term memory consistent with these having a role in memory consolidation.

neuroscience↗

bioRxiv2018

The Hex-Maze: A previous knowledge task for mice

New information is rarely learned in isolation, instead most of what we experience can be incorporated into or uses previous knowledge networks in some form. However, most rodent laboratory tasks assume the animal to be naive with no previous experience influencing the results. Previous knowledge in form of a schema can facilitate knowledge acquisition and accelerate systems consolidation: memories become more rapidly hippocampal independent and instead rely more on the prefrontal cortex. Here, we developed a new spatial navigation task where food locations are learned in a large, gangway maze - the HexMaze. Analysing performance across sessions as well as on specific trials, we can show simple memory effects as well as multiple effects of previous knowledge accelerating both online learning and performance increases over offline periods. Importantly, we are the first to show that schema build-up is dependent on how much time passes, not how often the animal is trained.

animal behavior and cognition↗

bioRxiv2017

The Object Space Task for mice and rats

Declarative memory encompasses representations of specific events as well as knowledge extracted by accumulation over multiple episodes. To investigate how these different sorts of memories are created, we developed a new behavioral task in rodents. The task consists of three distinct conditions (stable, overlapping, random). Rodents are exposed to multiple sample trials, in which they explore objects in specific spatial arrangements. In the stable condition, the locations are constant during all sample trials; in the test trial, one objects location is changed. In the random condition, object locations are presented in the sample phase without a specific spatial pattern. In the overlapping condition, one location is shared (overlapping) between all trials while the other location changes during sample trials. We show that in the overlapping condition, instead of only remembering the last sample trial, rodents form a cumulative memory of the sample trials.\n\nHere we could show that both mice and rats can accumulate information across multiple trials and express a long-term abstracted memory.

animal behavior and cognition↗

bioRxiv2017

2D:4D and spatial abilities: From rats to humans

Variance in spatial abilities are thought to be determined by in utero levels of testosterone and oestrogen, measurable in adults by the length ratio of the 2nd and 4th digit (2D:4D). We confirmed the relationship between 2D:4D and spatial performance using rats in two different tasks (paired-associate task and watermaze) and replicated this in humans. We further clarified anatomical and functional brain correlates of the association between 2D:4D and spatial performance in humans.

neuroscience↗