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Lechelon, M.

Publications and source records attributed to Lechelon, M..

2 recordsLinked to original sources

The Towers Foraging Park: A Flexible Naturalistic Framework to Study Learning, Decision-Making, and Motor Control in Freely Moving Mice

Adaptive behavior depends on a variety of brain functions, such as learning, decision-making, spatial navigation and motor control, which have been studied using two main strategies. Trial-based tasks allow their mechanistic dissection but tend to generate highly stereotypical behavior, whereas open-field investigations capture naturalistic dynamics with less experimental control. To leverage the strengths of both approaches, we developed a behavioral framework which recreates dilemmas faced by animals during patch foraging. In the Tower Foraging Park (TFP), mice harvest rewards along square towers (patches) by making quarter-turns around them in a single direction (exploit) and alternating between towers (explore) as patches eventually deplete. Within a couple of sessions, naive mice performed quarter-turns in the rewarded direction with increasing vigor and reduced variability, and switched towers after short exploitation bouts. When the harvest direction was reversed, mice rapidly adapted their turning direction, with quarter-turn trajectory variability and speed becoming decoupled. Mice subjected to daily reversals adapted progressively faster, revealing meta-learning. When the next rewarding tower became harder to locate, all trained mice increased exploitation duration, although metalearners outperformed animals trained under stable contingencies. Altogether, the TFP produced behavior consistent with foraging theory and revealed new processes facilitating flexible foraging: meta-learning and the decoupling of movement variability and speed. Moreover, because the TFP accommodates diverse protocol variants, adheres to FAIR principles, and is fully compatible with modern neurophysiological techniques, it provides a promising platform for mechanistic investigations of brain functions underlying adaptive behavior while maintaining ethological validity.

animal behavior and cognition↗

Light-inducible T cell engagers trigger, tune and shape the activation of primary T cells

To mount appropriate responses, T cells integrate complex sequences of receptor stimuli perceived during transient interactions with antigen presenting cells. Although it has been hypothesized that the dynamics of these interactions influence the outcome of T cell activation, methodological limitations have hindered its formal demonstration. Here, we have engineered the Light-inducible T cell engager (LiTe) system, a recombinant optogenetics-based molecular tool targeting the T Cell Receptor (TCR). The LiTe system constitutes a reversible molecular switch displaying exquisite reactivity. As proof of concept, we dissect how specific temporal patterns of TCR stimulation shape T cell activation patterns. We established that CD4+ T cells respond to intermittent TCR stimulation more efficiently than their CD8+ T cells counterparts and provide evidence that distinct sequences of TCR stimulation encode different cytokine programs. Finally, we show that the LiTe system could be exploited to create light-activated bispecific T cell engagers and manipulate tumor cell killing. Overall, the LiTe system provides new opportunities to understand how T cells integrate TCR stimulations and to trigger T cell cytotoxicity with a high spatiotemporal control.

immunology↗