Biology subjects

Kropff, E.

Publications and source records attributed to Kropff, E..

4 recordsLinked to original sources

bioRxiv2025

Audiovisual gamma stimulation enhances hippocampal neurogenesis and neural circuit plasticity in aging mice

Gamma oscillations are disrupted in various neurological disorders, including Alzheimers disease (AD). In AD mouse models, non-invasive audiovisual stimulation (AuViS) at 40 Hz enhances gamma oscillations, clears amyloid-beta, and improves cognition. We investigated mechanisms of circuit remodeling underlying these restorative effects by leveraging the sensitivity of hippocampal neurogenesis to activity in middle-aged wild-type mice. AuViS increased progenitor cell proliferation, neuronal differentiation and morphological maturation of newborn granule cells, promoting their synaptic integration. While visual or auditory stimuli alone induced dendritic growth, axonal changes required combined audiovisual stimulation. The actions of AuViS involved neurotrophin pathways, as shown by the lack of effect upon TrkB signaling blockade. These results reveal widespread plasticity mechanisms triggered by AuViS, a therapeutic approach currently proposed for treating neurological disorders in humans.

neuroscience↗

bioRxiv2024

The dentate gyrus provides flexibility for efficient spatial navigation

The hippocampus plays a critical role in spatial navigation and declarative memory. The dentate gyrus is the neurogenic region of the hippocampal formation and it has long been implicated in the fine separation of similar contexts or close object locations. However, it is unclear how an accurate discrimination could be beneficial to a goal-guided behavior in a changing environment. Therefore, we used chemogenetic inhibition to study the role of the dentate gyrus in a goal-guided spatial navigation paradigm over a familiar but dynamic crossword maze. Mice were challenged to localize a novel reward location from alternative pathways in two versions of the task with particular configurations in each experimental day. In the simple task, the two optimal paths to the goal shared some segments in their trajectory. In a more complex task, optimal trajectories demanded completely different directions to the reward location. Overall, mice with chemogenetic inhibition of the dentate gyrus were able to learn all the routes regardless the complexity of the task, similarly to control animals. However, after having solved a first route in the complex task, mice with dentate gyrus inhibition displayed an impairment to efficiently navigate over the alternate path. Our results demonstrate a role of the dentate gyrus in cognitive flexibility required to reach a goal in a changing familiar environment.

animal behavior and cognition↗

bioRxiv2022

Unique potential of immature adult-born neurons for the remodeling of CA3 spatial maps

Mammalian hippocampal circuits undergo extensive remodeling through adult neurogenesis. While this process has been widely studied, the specific contribution of adult-born granule cells (aGCs) to spatial operations in the hippocampus remains unknown. Here we show that optogenetic activation of 4-week-old (young) aGCs in free-foraging mice produces a non- reversible reconfiguration of spatial maps in proximal CA3, while rarely evoking neural activity. Stimulation of the same neuronal cohort on subsequent days recruits CA3 neurons with increased efficacy but fails to induce further remapping. In contrast, stimulation of 8- week-old (mature) aGCs can reliably activate CA3 cells but produce no alterations in spatial maps. Our results reveal a unique role of young aGCs in remodeling CA3 representations, a potential that can be depleted and is lost with maturation. This ability could contribute to generate orthogonalized downstream codes supporting pattern separation.

neuroscience↗

bioRxiv2022

Modeled grid cells aligned by a flexible attractor

Entorhinal grid cells implement a spatial code with hexagonal periodicity, signaling the position of the animal within an environment. Grid maps of cells belonging to the same module share spacing and orientation, only differing in relative two-dimensional spatial phase, which could result from being part of a two-dimensional attractor guided by path integration. However, this architecture has the drawbacks of being complex to construct and rigid, path integration allowing for no deviations from the hexagonal pattern such as the ones observed under a variety of experimental manipulations. Here we show that a simpler one-dimensional attractor is enough to align grid cells equally well. Using topological data analysis, we show that the resulting population activity is a sample of a torus, while the ensemble of maps preserves features of the network architecture. The flexibility of this low dimensional attractor allows it to negotiate the geometry of the representation manifold with the feedforward inputs, rather than imposing it. More generally, our results represent a proof of principle against the intuition that the architecture and the representation manifold of an attractor are topological objects of the same dimensionality, with implications to the study of attractor networks across the brain.

neuroscience↗