Biology subjects

Mosser, C.-A.

Publications and source records attributed to Mosser, C.-A..

7 recordsLinked to original sources

bioRxiv2024

Predictive Coding of Reward in the Hippocampus

A fundamental objective of the brain is to anticipate future outcomes1-7. This process requires learning the states of the world as well as the transitional relationships between those states. The hippocampal cognitive map is believed to be one such internal model8. However, evidence for predictive coding9-12 and reward sensitivity13-19 in the hippocampal neuronal representation suggests that its role extends beyond purely spatial representation. In fact, it raises the question of what kind of spatial representation is most useful for learning and maximizing future rewards? Here, we track the evolution of reward representation over weeks as mice learn to solve a cognitively demanding reward-based task. Our findings reveal a highly organized restructuring of hippocampal reward representations during the learning process. Specifically, we found multiple lines of evidence, both at the population and single-cell levels, that hippocampal representation becomes predictive of reward over weeks. Namely, both population-level information about reward and the percentage of reward-tuned neurons decrease over time. At the same time, the representation of the animals choice and reward approach period (the period between choice and reward) increased over time. By tracking individual reward cells across sessions, we found that neurons initially tuned for reward shifted their tuning towards choice and reward approach periods, indicating that reward cells backpropagate their tuning to anticipate reward with experience. These findings underscore the dynamic nature of hippocampal representations, highlighting their critical role in learning through the prediction of future outcomes.

neuroscience↗

bioRxiv2023

A population code for idiothetic representations in the hippocampal-septal circuit

The hippocampus is a higher-order brain structure responsible for encoding new episodic memories and predicting future outcomes. In absence of external stimuli, neurons in the hippocampus express sequential activities which have been proposed to support path integration by tracking elapsed time, distance traveled, and other idiothetic variables. On the other hand, with sufficient external sensory inputs, hippocampal neurons can fire with respect to allocentric cues. Previously, these idiothetic codes have been described in conditions where running speed is clamped experimentally. To this day, the exact determinants of idiothetic representations during free navigation remain unclear. Additionally, whether CA1 and CA3 temporal and distance codes are transmitted downstream to the lateral septum has not been established. Here, we develop an unsupervised model trained to compress neural information with minimal loss, and find that we can efficiently decode elapsed time and distance traveled from low-dimensional embeddings of neural activity in freely moving mice. We also developed unbiased information metrics that are minimally sensitive to quantization parameters and enable comparisons across modalities and brain regions. In more than 30,000 CA1 pyramidal neurons, we show that spatiotemporal information is represented as a mixture of idiothetic and allocentric information, the balance of which is dictated by task demand and environmental conditions. In particular, we find that a subset of CA1 pyramidal neurons encode the spatiotemporal distance to rewards. Single cell and population statistics across the hippocampal-septal circuit reveal that idiothetic variables emerge in CA1 and are integrated postsynaptically in the lateral septum. Finally, we implement a computational model trained to replicate real world neural activity, and find that grid cells could provide a plausible input for CA1 representations of time and distance. Altogether, our results suggest that hippocampal CA1 continuously integrates both idiothetic and allocentric signals depending on task demand and available cues, and these high-level representations are effectively transmitted to downstream regions.

neuroscience↗

bioRxiv2021

Extended experience reveals distinct representational dynamics governing the CA1 spatial code

The hippocampus is thought to mediate episodic memory through the instantiation and reinstatement of context-specific cognitive maps. However, recent longitudinal experiments have challenged this view, reporting that most hippocampal cells change their tuning properties over days even in the same environment. Often referred to as representational drift, these dynamics raise multiple questions about the representational capacity and content of the hippocampal code. One such question is whether and how these dynamics impact the contextual code. To address this, here we imaged large CA1 populations over more than a month of daily experience as freely behaving mice participated in an extended geometric morph paradigm. We find that long-timescale changes in population activity occurred orthogonally to the representation of context in network space, allowing for consistent readout of contextual information across weeks. Together, these results demonstrate that long-timescale changes to the CA1 spatial code preserve the relative structure of contextual representation.

neuroscience↗

bioRxiv2020

Conjunctive spatial and idiothetic codes are topographically organized in the lateral septum

The hippocampal spatial codes relevance for downstream neuronal populations - particularly its major subcortical output the lateral septum (LS) - is still poorly understood. Here, using calcium imaging combined with unbiased analytical methods, we functionally characterized and compared the spatial tuning of LS GABAergic cells to those of dorsal CA3 and CA1 cells. We identified a significant number of LS cells that are modulated by place, speed, acceleration, and direction, as well as conjunctions of these properties, directly comparable to hippocampal CA1 and CA3 spatially modulated cells. Interestingly, Bayesian decoding of position based on LS spatial cells reflected the animals location as accurately as decoding using the activity of hippocampal pyramidal cells. A portion of LS cells showed stable spatial codes over the course of multiple days, potentially reflecting long-term episodic memory. The distributions of cells exhibiting these properties formed gradients along the anterior-posterior and dorsal-ventral axes of the LS, directly reflecting the topographical organization of hippocampal inputs to the LS. Finally, we show using trans-synaptic tracing that LS neurons receiving CA3 and CA1 excitatory input send projections to the hypothalamus and medial septum, regions that are not targeted directly by principal cells of the dorsal hippocampus. Together, our findings demonstrate that the LS accurately and robustly represents spatial, directional as well as self-motion information and is uniquely positioned to relay this information from the hippocampus to its downstream regions, thus occupying a key position within a distributed spatial memory network.

neuroscience↗

bioRxiv2020

The McGill-Mouse-Marmoset Platform: A Standardized Approach for High-throughput Imaging of Neuronal Dynamics During Behavior

Understanding the rules that govern neuronal dynamics throughout the brain to subserve behavior and cognition remain one of the biggest challenges in neuroscience research. Recent technical advances enable the recording of increasingly larger neuronal populations to produce increasingly more sophisticated datasets. Despite bold and important open-science and data-sharing policies, these datasets tend to include unique data acquisition methods, behavior, and file structures. Discrepancies between experimental protocols present several key challenges including the analysis of the data itself, comparison of data collected between laboratories, and for the comparison of dynamics between brain regions and species. Here, we discuss our recent efforts to create a standardized and high-throughput research platform to address these issues. The McGill-Mouse-Marmoset (M3) platform combines miniscope calcium imaging recording in both mice and marmosets with standardized touchscreen-based behavioral testing. The goal is to curate an open-source and standardized framework for acquiring, analyzing, and accessing high-quality data of the neuronal dynamics that underly cognition throughout the brain in mice, marmosets, and models of disease. We end with a discussion of future developments and a call for users to adopt this standardized approach.

neuroscience↗

bioRxiv2019

Fat food exacerbates post-prandial hypothalamic inflammation involving GFAP+ cells and microglia

In humans, obesity was associated with brain inflammation and glial cell proliferation. Studies in rodents showed that glial cell proliferation occurs within 24 hours of high-fat diet (HFD) consumption, before obesity development. This proliferation was mainly observed in the hypothalamus (HT), a crucial brain structure for controlling body weight. Therefore, we sought to characterize the post-prandial HT inflammatory response to 1-3-6 hours exposure to a standard diet and HFD. HFD exposure increased gene expression of astrocyte and microglial marker (GFAP and Iba1) compare to standard treated mice and induced morphological modifications of microglial cells in HT. This remodeling was associated with higher expression of inflammatory genes and differential activation of hypothalamic neuropeptides involved in energy balance regulation. DREADD and PLX5622 technologies, used to modulate GFAP-positive or microglial cells activity respectively, showed that both glial cell types are involved in hypothalamic post-prandial inflammation, but in a different time frame and with a diet specificity Thus, an exacerbated post-prandial inflammation in brain might predispose individuals to obesity and needs to be characterized to address this worldwide crisis.

neuroscience↗

bioRxiv2019

Biphasic impact of prenatal inflammation and macrophage depletion on the wiring of neocortical inhibitory circuits

The etiology of neurodevelopmental disorders is linked to defects in Parvalbumin (PV)-expressing cortical interneurons and to prenatal immune challenges. Mouse models of maternal immune activation (MIA) and microglia deficits increase the postnatal density of PV interneurons, raising the question of their functional integration. Here, we show that MIA and embryonic depletion of macrophages including microglia, have a two-step impact on PV interneurons wiring onto their excitatory target neurons in the barrel cortex. In adults, both challenges reduced the inhibitory drive from PV interneurons, as reported in neurodevelopmental disorders. In juveniles, however, we found an increased density of PV neurons, an enhanced strength of unitary connections onto excitatory cells and an aberrant horizontal inhibition with a reduced lateral propagation of sensory inputs in vivo. Our results provide a novel framework for understanding the impact of prenatal immune challenges onto the developmental trajectory of inhibitory circuits that leads to pathological brain wiring.

neuroscience↗