Search bioRxiv⌕ Search

Biology subjects

Bouchet, M.

Publications and source records attributed to Bouchet, M..

3 recordsLinked to original sources

Mice-side bias: Deliberative decision making in a model of rule revision reveals 'myside' confirmation bias-like cognitive processes in mice.

Confirmation or myside bias--over-valuation of novel information which confirms previously internalized cognitive content (prior beliefs, rules of conduct, etc.) and corresponding under-valuation of disconfirming novel information--constitutes a serious obstacle to adaptive revision of our beliefs, especially in ambiguous or complex epistemic environments. Indeed, myside bias has become a particularly pernicious fact of societal cohesion, contributing to the propagation of fake news, to social polarization, and even to the replication crisis in experimental science. By contrast, relatively little is understood about either its neurocognitive underpinnings or its evolution, one reason for this being that the potential presence of myside bias-like tendencies in non-human animals has never been directly tested. Hence, in order to advance research in both of these directions, we designed a novel mouse model of everyday-like rule revision such that the dynamic model environment would be sufficient to call out myside bias-like behaviors providing that mice did indeed possess the particular kind of competing neurocognitive processes necessary for it to manifest. Here, we both validate that model and provide the first behavioral descriptions of myside confirmation bias-like deliberative profiles in a non-human animal. Notably, we observe that this bias does not manifest in a merely unreflective or heuristic/ system 1 manner but rather also emerges through and indeed increases deliberative behaviors, especially in contexts of low representational resolution. Several other parallels with findings from human studies of myside bias are also detailed in the discussion.

neuroscience↗

To deliberate, remember; to anticipate, forget: Cognitive deliberation profiles underpinning active forgetting-dependent everyday-like memory performance in young and aged mice.

Recalling a specific past episode that will enable us to decide which action is suited to a given present situation is a core element of everyday life. A wealth of research has demonstrated that such selective remembering is dependent upon a capacity to inhibit or provisionally forget related yet inappropriate memory episodes which could orient behavior in unwilled directions. Everyday-like memory (EdM) refers to this type of common organizational mnemonic capacity, known to deteriorate significantly with age, putatively as a result of decline in the cognitive capacity for selective inhibition or active forgetting. Moreover, this memory retrieval-concomitant active forgetting comes at the cost of genuine amnesic weakening of the inhibited episodes, a phenomenon referred to as retrieval-induced forgetting (RIF). In the present study, we introduce a novel characterization of our previously validated mouse model of EdM in terms of the existing active forgetting and RIF literature. We also introduce novel behavioral analyses of the deliberation processes elicited by EdM challenge and use detailed multi-factorial explorations to reveal how these processes are impacted by age, temporal retention demand, difficulty of EdM challenge, and anticipation of trial outcome. Our observations indicate that deliberation requires remembering while accurate anticipation--in which a critical age-related deficit is also observed--requires active forgetting. Our results represent a significant advance towards unifying our understanding of the neurocognitive processes underpinning everyday-like memory, RIF, mnemonic deliberation, anticipatory function, and how they all are impacted by the physiological ageing process. In parallel, we present preliminary results using a transgenic mouse model which point to a fundamental role for the endocannabinoid system (eCS) in active forgetting and EdM, thereby demonstrating that deeper investigation of previously characterized age-related decline of the eCS should be a pre-clinical priority with a view to developing treatments for age-related decline of EdM function.

animal behavior and cognition↗

The post-transcriptional regulation of TFs in immature motoneurons shapes the axon-muscle connectome

Temporal factors expressed sequentially in neural stem cells, such as RNA binding proteins (RBPs) or transcription factors (TFs), are key elements in the generation of neuronal diversity. The molecular mechanism underlying how the temporal identity of stem cells is decoded into their progeny to generate neuronal diversity is largely unknown. Here, we used genetic and new computational tools to study with precision the unique fates of the progeny of a stem cell producing 29 morphologically distinct leg motoneurons (MNs) in Drosophila. We identified 40 TFs expressed in this MN lineage, 15 of which are expressed in a combinatorial manner in immature MNs just before their morphological differentiation. By following TF expression patterns at an earlier developmental stages, we discovered 19 combinatorial codes of TFs that were progressively established in immature MNs as a function of their birth order. The comparison of the RNA and protein expression profiles of 6 TFs revealed that post-transcriptional regulation plays an essential role in shaping these TF codes. We found that the two known RBPs, Imp and Syp, expressed sequentially in neuronal stem cells, are upstream regulators of the TF codes. Both RBPs are key players in the construction of axon-muscle connectome through the post-transcriptional regulation of 5 of the 6 TFs examined. By deciphering the function of Imp in the immature MNs with respect to the stem cell of the same lineage, we propose a model where RBPs shape the morphological fates of MNs through post-transcriptional regulation of TF codes in immature MNs. Taken together, our study reveals that immature MNs are plastic cells that have the potential to acquire many morphological fates. The molecular basis of MN plasticity originates in the broad expression of different TF mRNA, that are post-transcriptionally shaped into TF codes by Imp and Syp, and potentially by other RBPs that remain to be discovered, to determine their morphological fates.

developmental biology↗