Biology subjects

Delord, B.

Publications and source records attributed to Delord, B..

5 recordsLinked to original sources

bioRxiv2026

Kainate receptors are critical for permissivity to sustained, disorganized and network-wide pathological activity in the epileptic dentate gyrus

In temporal lobe epilepsy, the dentate gyrus (DG) undergoes extensive reorganization through recurrent mossy fiber (rMF) sprouting, involving both AMPA and kainate receptors (KARs) at granule cell-to-granule cell (GC-GC) recurrent synapses. While KARs are known to enhance neural excitability, their specific contribution to the dynamics of the epileptogenic GC-GC network remains poorly understood. Here, by building and assessing a DG network model endowed with KARs, we revealed that the slow excitatory postsynaptic potentials (EPSPs) they mediate, in synergy with persistent sodium currents, profoundly reshape epileptogenic dynamics by facilitating the conditions for pathological activity, through two complementary mechanisms. Regarding input processing, KARs extended the window for temporal integration in GCs, favoring the initiation of network aberrant activities in response to more dispersed input patterns. Concerning network interactions, KARs reduced the number of sprouted connections needed for the development of epileptiform discharges. In fact, the extension of the structural and functional parameter region driving epileptiform activity was effective both for their initiation and, critically, their sustained maintenance. Moreover, KARs drove a striking transition in network behaviour, from partially organized collective dynamics to a highly disordered regime. In their presence, massive firing propagated through the DG network, disrupting spatial and temporal spiking patterns. This resulted in increased activity dimensionality and entropy, together with reduced mutual information between neurons. Altogether, our results suggest that KARs are not merely amplifiers of network excitation but critical determinants that fundamentally reshape the dynamical landscape, rendering the sprouted DG network permissive to self-sustaining pathological activity.

neuroscience↗

bioRxiv2025

Dopaminergic mechanisms of dynamical social specialization in mouse microsocieties

Social organization and division of labor are fundamental to animal societies, but how do these structures emerge from individual interactions, and what role does neuromodulation play in shaping them? Using behavioral tracking in a semi-natural environment, neural recordings, and computational models integrating reinforcement and social learning, we show that groups of three isogenic mice spontaneously develop specialized roles while solving a foraging task requiring individual decisions under social constraints. Moreover, these roles are shaped by dopaminergic activity in the ventral tegmental area. Strikingly, despite minor sex-differences in behavior when mice were tested alone, male triads formed stable worker-scrounger relationships driven by competition, whereas female triads adopted uniform, cooperative strategies. Model analysis revealed how intra- and inter-sex parameter differences in resource exploitation, combined with contingent and dynamic social interactions, drive behavioral specialization and labor division. Most notably, it highlighted how contingency, amplified by competition, magnifies individual differences and shapes social profiles. The plastic, adaptive nature of social organization within triads was confirmed by manipulating dopaminergic cell activity, which reshaped social roles and altered group structure. Our findings support a feedback loop where social context shapes neural states, which in turn reinforce behavioral specialization and stabilize social structures.

neuroscience↗

bioRxiv2022

Biophysical control of neural trajectories under disordered brain dynamics

Neural representations rely on the ability of neuronal assemblies to display organized spiking patterns, despite being embedded within noisy networks. These structured patterns arise from attractor dynamics due to activity reverberation promoted by learnt assembly connectivity. Yet, attractor dynamics have been assessed either under low-noise conditions or in highly idealized neuronal assemblies. Here, in a spiking recurrent neural network model displaying asynchronous irregular noise, we show that realistic spike timing-dependent plasticity (STDP) imposes either low controllability of attractor recall (when STDP is strong), low stability of attractor maintenance (when STDP is low), or both. Moreover, STDP-built attractors display low independence, i.e., they perturb activity in the surrounding network. These constraints may favor self-generated representation switches essential for cognitive flexibility but dampening cognitive reliability. We reveal, by contrast, that several biophysical mechanisms alleviate these issues through a common dynamical principle, protecting excitatory-driven attractorial dynamics from inhibitory-driven spontaneous fluctuations. Amongst biophysical determinants, intrinsic properties were most efficient to increase controllability, stability and independence of attractor dynamics. Specifically, spike-triggered calcium-activated conductances improved reliability by mitigating reliance on connectivity, even at low conductance levels, i.e., in the absence of cell-autonomous intrinsic bistability. Finally, we show that the mechanisms we identify operate over a large repertoire of static (e.g., Hebbian or ring) and dynamic (e.g., sequences) attractors, with uni- and bidirectional propagation. Altogether, these results pinpoint synaptic and intrinsic synergy as a generic principle to regulate attractor reliability, as a function of the cognitive demand.

neuroscience↗

bioRxiv2022

Dopamine builds and reveals reward-associated latent behavioral attractors

Phasic variations in dopamine levels are interpreted as a teaching signal reinforcing rewarded behaviors. However, behavior also depends on the online, neuromodulatory effect of phasic dopamine signaling. Here, we unravel a new neurodynamical principle that reconciles these roles. In a biophysical recurrent network-based decision architecture, we showed that dopamine-mediated synaptic plasticity stabilized neural assemblies representing rewarded locations as latent, local attractors. Dopamine-modulated synaptic excitability activated these attractors online, and they became accessible as internal goals, even from remote animal positions. We experimentally validated these predictions in mice, using optogenetics, by demonstrating that online dopamine signaling specifically attracts animals toward rewarded locations, without off-target motor effects. We therefore propose that online dopamine signaling reveals potential goals by widening and deepening the basin of dopamine-built attractors representing rewards.

neuroscience↗

bioRxiv2020

Local inhibitory control of frontal network metastability underlies the temporal signature of cognitive states

Cortical neural dynamics organizes over multiple anatomical and temporal scales. The mechanistic origin of the temporal organization and its contribution to cognition remain unknown. Here we demonstrate the cause of this organization by studying a specific temporal signature (autocorrelogram time constant and latency) of neural activity. In monkey frontal areas, recorded during flexible cognitive decisions, temporal signatures display highly specific area-dependent ranges, as well as anatomical and cell-type distributions. Moreover, temporal signatures are functionally adapted to behaviorally relevant timescales. Fine-grained biophysical network models, constrained to account for temporal signatures, reveal that after-hyperpolarization potassium and inhibitory GABA-B conductances critically determine areas specificity. They mechanistically account for temporal signatures by organizing activity into metastable states, with inhibition controlling state stability and transitions. As predicted by models, state durations non-linearly scale with temporal signatures in monkey, matching behavioral timescales. Thus, local inhibitory-controlled metastability constitutes the dynamical core specifying the temporal organization of cognitive functions in frontal areas.

neuroscience↗