Biology subjects

Boraud, T.

Publications and source records attributed to Boraud, T..

4 recordsLinked to original sources

bioRxiv2024

Reward-driven adaptation of movements requires strong recurrent basal ganglia-cortical loops

The basal ganglia (BG) are a collection of subcortical nuclei involved in motor control, sensorimotor integration, and procedural learning. They play a key role in the acquisition and adaptation of movements, a process driven by dopamine-dependent plasticity at cortico-striatal projections, which serve as BG input. However, BG output is not necessary for executing many well-learned movements. This raises a fundamental question: how can plasticity at BG input contribute to the acquisition and adaptation of movements which execution does not require BG output? Existing models of BG function often neglect the feedback dynamics within cortico-BG-thalamo-cortical circuitry and do not capture the interaction between the cortex and BG in movement generation and adaptation. In this work, we address the above question in a theoretical model of the BG-thalamo-cortical multiregional network, incorporating anatomical, physiological, and behavioral evidence. We examine how its dynamics influence the execution and reward-based adaptation of reaching movements. We demonstrate how the BG-thalamo-cortical network can shape cortical motor output through the combination of three mechanisms: (i) the diverse dynamics emerging from its closed-loop architecture, (ii) attractor dynamics driven by recurrent cortical connections, and (iii) reinforcement learning via dopamine-dependent cortico-striatal plasticity. Our study highlights the role of the cortico-BG-thalamo-cortical feedback in efficient visuomotor adaptation. It also suggests a mechanism for early-stage acquisition of reaching movements through motor babbling. More generally, our model explains how the BG-cortical network refines motor output through its intricate closed-loop dynamics and dopamine-dependent plasticity at cortico-striatal synapses. Significance statementThe basal ganglia (BG) are essential for learning and adapting movements, yet their output is often unnecessary for executing well-learned actions. This paradox challenges existing models of BG function. Here, we present a biologically grounded model of the cortico-BG-thalamo-cortical loop, showing how this closed-loop network supports efficient motor adaptation and early movement acquisition. Our findings reveal that dopamine-driven plasticity, recurrent cortical dynamics, and feedback from the BG together shape motor output, even when BG output is not directly required for execution. This work provides a unified framework explaining how the BG-cortical circuit contributes to both learning and refinement of goal-directed actions.

neuroscience↗

bioRxiv2024

On the epistemic role of hippocampal cells: the case of splitter cells

During the past decades, hippocampal formation has undergone extensive studies, leading researchers to identify a vast collection of cells with functional properties. Several investigations, supported by carefully crafted models, have examined the origin of such cells. The most recent models hypothesize that temporal sequences underlie the observed spatial properties. We aim at investigating whether a random recurrent structure is sufficient to allow such latent sequence to appear. To do so, we simulated an agent with egocentric sensory inputs that must navigate and alternate choices at intersections. We were subsequently able to identify several splitter cells inside the model. Remarkably, when we systematically lesioned the identified splitter cells, the models behavioral performance remained intact: in the vast majority of cases, new splitter cells re-emerged through network reorganization, while in the remaining cases, the task was solved without any detectable splitter cells, demonstrating that splitter cells are not necessary to the task resolution. Position, orientation, and decision representations could also be successfully decoded from the reservoir activity, even after repeated lesioning. Subspace alignment analysis further revealed that this reorganization preserves the task-relevant population geometry while redistributing activity within the null sub-space, with the trajectory-encoding dimension rotating in neuron space across lesions. Together, these findings demonstrate that splitter cell activity is primarily task-driven and does not derive from a specific architecture or learning rule: splitter cells emerge generically across random recurrent networks that successfully solve the task, across a broad and robust range of dynamical parameters, and are not necessary for task performance. Our results therefore challenge the notion of functional necessity for specific neural populations.

neuroscience↗

bioRxiv2020

In vivo electrophysiological validation of DREADD-based inhibition of pallidal neurons in the non-human primate.

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are widely used in rodents to manipulate neuronal activity and establish causal links between structure and function. Their utilization in non-human primates (NHPs) is however limited and their efficacy still debated. Here, we tested DREADD expression in the NHP external globus pallidus (GPe) and electrophysiologically validated DREADD-based inhibition of GPe neurons in the anesthetized monkey.To do so, we performed intracerebral injections of viral construct expressing hM4Di receptor under a neuron-specific promoter into the GPe. Then, we recorded the neuronal activity in the DREADD-transduced (test condition) and DREADD-free (control condition) GPe of two anesthetized animals following local intra-GPe microinjection of clozapine-N-oxide (CNO). In total, 19 and 8 well-isolated and stable units were recorded in the DREADD-transduced and DREADD-free GPe, respectively. Overall, we found that almost half (9/19) of the units modulated their activity following CNO injection in DREADD-transduced GPe. Surprisingly, neuronal activity of the GPe units exhibited diverse patterns in timing and polarity (increase/decrease) of firing rate modulations during and after CNO injection. Nevertheless, decreases were exclusive and stronger after CNO injection. In contrast, only one unit modulated its activity after CNO injection in DREADD-free GPe. Moreover, post-mortem histochemical analysis revealed that hM4Di DREADDs were expressed at high level in the GPe neurons located in the vicinity of the viral construct injection sites. Our results therefore show in vivo DREADD-based inhibition of pallidal neurons in the NHP model and reinforce the view that DREADD technology can be effective in NHPs.

neuroscience↗

bioRxiv2017

Dual Competition between the Basal Ganglia and the Cortex: from Action-Outcome to Stimulus-Response

Action-outcome (A-O) and stimulus-response (S-R) processes that are two forms of instrumental conditioning that are important components of decision making and action selection. The former adapts its response according to the outcome while the latter is insensitive to the outcome. An unsolved question is how these two processes emerge, cooperate and interact inside the brain in order to issue a unique behavioral answer. Here we propose a model of the interaction between the cortex, the basal ganglia and the thalamus based on a dual competition. We hypothesize that the striatum, the subthalamic nucleus, the internal pallidum (GPi), the thalamus, and the cortex are involved in closed feedback loops through the hyperdirect and direct pathways. These loops support a competition process that results in the ability for the basal ganglia to make a cognitive decision followed by a motor decision. Considering lateral cortical interactions (short range excitation, long range inhibition), another competition takes place inside the cortex allowing this latter to make a cognitive and a motor decision. We show how this dual competition endows the model with two regimes. One is oriented towards action-outcome and is driven by reinforcement learning, the other is oriented towards stimulus-response and is driven by Hebbian learning. The final decision is made according to a combination of these two mechanisms with a gradual transfer from the former to the latter. We confirmed these theoretical results on primates using a two-armed bandit task and a reversible bilateral inactivation of the internal part of the globus pallidus.

neuroscience↗