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Monyer, H.

Publications and source records attributed to Monyer, H..

8 recordsLinked to original sources

Distinct medial septal GABAergic pathways differentially regulate spatial memory and network activity

Septal GABAergic projection neurons form distinct pathways to subregions of the hippocampal formation, including the hippocampus proper and the medial and lateral entorhinal cortices. Parvalbumin (PV+) and calbindin expressing (CB+) projections target different types of interneurons and thereby differentially regulate neuronal activity in the downstream area. Consistent with the idea of dissociable functional roles, inhibition of septal PV+ neurons impairs reference memory whereas inhibition of septal CB+ neurons impairs both reference and working memory. Here, we show that these functions are differentially supported by specific projection pathways: PV+ projections to the dorsal hippocampus and medial entorhinal cortex (MEC) support reference memory, whereas CB+ projections to the MEC support both reference and working memory. At the network level, septal PV+, but not CB+, neurons regulate theta oscillations. Together, these findings further define the roles of septal PV+ and CB+ pathways in orchestrating network activity and supporting specific forms of memory.

neuroscience↗

Prior experience dynamically determines differential cue weighting in the medial entorhinal cortex

Spatial navigation depends on integrating multiple cue sets whose influence is determined primarily by their inferred reliability. Here we investigated how cue weighting in the medial entorhinal cortex is updated based on previous experience at different time scales (minutes vs. days). In mice recorded in light and darkness while manipulating coherence between distal room cues and local arena cues, grid cells displayed stable firing fields in darkness only when prior light experience maintained coherent cue relationships. Grid activity remained anchored to local cues, and stability continuously increased by repeated exposure. In contrast, mice that experienced cue mismatch in light showed markedly reduced grid stability in darkness. Strikingly, re-establishing cue coherence produced only partial recovery, whereas a single exposure to cue mismatch abolished reliance on local cues. The reference frame shift at different time scales reflects a dynamic balance between flexibility and stability determined by a conservative cue weighting strategy.

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Shared early impairments of medial entorhinal cortex function across distinct Alzheimer's disease etiologies

The medial entorhinal cortex (MEC) harbors diverse spatially and object-tuned cell types essential for spatial coding and episodic memory, and is among the earliest regions affected in neurodegenerative diseases. Here, we examined how early neurodegeneration alters MEC cellular coding, network dynamics, and behavior in two Alzheimer mouse models of distinct etiology. Specifically, we performed in vivo electrophysiology, immunohistochemistry and behavioral assays in models that reflect the manifestation of a tauopathy and amyloidopathy, respectively, to identify common impairments. In both models, the earliest deficits manifested as instability of spatial context representations at the cellular and behavioral level. These impairments preceded model-specific disruptions in grid cell coding and altered theta oscillations. We further identified reduced parvalbumin-positive (PV+) septal projections as a likely contributor to MEC dysfunction. In contrast, object-vector coding remained intact, highlighting spatial context instability as an early marker of MEC impairment.

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Oxytocin facilitates social behavior of female rats via selective modulation of interneurons in the medial prefrontal cortex

The hypothalamic neuropeptide oxytocin is best known for its prosocial behavioral effects. However, the precise anatomical and cellular targets for oxytocin in the cortex during social behavior remain elusive. Here we show that oxytocin neurons project directly to the medial prefrontal cortex where evoked axonal oxytocin release facilitates social behaviors in adult female rats. In conjunction, we report that local oxytocin receptor-expressing (OTR+) cells are predominantly interneurons, whose activation promotes social interaction. Notably, this prosocial effect persists even under physiological challenge (hunger), pointing to a dedicated prosocial circuit capable of overriding primary survival drives. We further demonstrate that activation of these OTR+ interneurons inhibits principal cells specifically projecting to the basolateral amygdala, thus providing a putative mechanism of selective oxytocin action in this sociability-promoting cortical network.

neuroscience↗

Grid cells perform path integration in multiple reference frames during self-motion-based navigation

With their periodic firing pattern, grid cells are considered a fundamental unit of a neural network performing path integration. The periodic firing patterns of grid cells have been observed mainly during behaviors with little navigational demands, and the firing patterns of grid cells in animals navigating 2D environments using path integration are largely unknown. Here, we recorded the activity of grid cells in mice performing the AutoPI task, a task assessing homing based on path integration. Using artificial deep neural networks to decode the animals moment-to-moment movement vectors, we found that grid cells perform path integration over short trajectories and change their reference frames within single trials. More specifically, grid cell modules re-anchor to a task-relevant object via a translation of the grid pattern. The code for movement direction in grid modules drifts as the animal navigates using self-motion cues, and this drift predicts the homing direction of the mouse. These results reveal the computations in grid cell circuits during self-motion-based navigation.

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Spatial transcriptomics map of the embryonic mouse brain: a tool to explore neurogenesis

The developing brain has a well-organized anatomical structure comprising different types of neural and non-neural cells. Stem cells, progenitors, and newborn neurons tightly interact with their neighbouring cells and tissue microenvironment, and this intricate interplay ultimately shapes the output of neurogenesis. Given the relevance of spatial cues during brain development, we acknowledge the necessity for a spatial transcriptomics map accessible to the neurodevelopmental community. To fulfil this need, we generated spatially-resolved RNAseq data from E13.5 mouse brain sections immunostained for mitotic active neural and vascular cells. Unsupervised clustering defined specific cell type populations of diverse lineages and differentiation states. Differential expression analysis revealed unique transcriptional signatures across specific brain areas, uncovering novel features inherent to particular anatomical domains. Finally, we integrated existing single-cell RNAseq datasets into our Spatial Transcriptomics map, adding tissue context to single-cell RNAseq data. In summary, we provide a valuable tool that enables the exploration and discovery of unforeseen molecular players involved in neurogenesis, particularly in the crosstalk between different cell types. Summary StatementDi Marco, Vazquez-Marin et al. provide an open-access spatial transcriptomics atlas of the embryonic mouse brain. This spatial map enables the exploration and discovery of gene functions within tissue context.

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Distinct spatial maps and multiple object codes in the lateral entorhinal cortex

The lateral entorhinal cortex (LEC) is a major cortical input area to the hippocampus and it is crucial for associative object-place-context memories. An unresolved question is whether these associations are performed exclusively in the hippocampus or also upstream thereof. Anatomical evidence suggests that the LEC processes both object and spatial information. We here describe a gradient of spatial selectivity along the antero-posterior axis of the LEC. We demonstrate that the LEC generates distinct spatial maps for different contexts that are independent of object coding and vice versa, thus providing evidence for pure spatial and pure object codes upstream of the hippocampus. Whilst space and object coding occur by and large separately in the LEC, we identified neurons that encode for space and objects conjunctively. Together, these findings point to a scenario in which the LEC sustains both distinct space and object coding as well as associative space-object coding.

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Septal GABAergic Inputs to CA1 Govern Contextual Memory Retrieval

Whether projections from the medial septum regulate the function of the CA1 hippocampus in episodic memory retrieval is not known. Here we show that septal GABAergic inputs to CA1 promote contextual fear memory, blocking the activation of parvalbumin-rich interneurons to facilitate Erk/MAP-kinase signaling in pyramidal cells during retrieval. Thus, suppression of feed-forward inhibition onto CA1 by septal GABAergic neurons gates contextual fear behavior.

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