Biology subjects

Vandecasteele, M.

Publications and source records attributed to Vandecasteele, M..

4 recordsLinked to original sources

bioRxiv2025

The gut-brain vagal axis governs mesolimbic dopamine dynamics and reward events

Reward-related processes have traditionally been ascribed to neural circuits centered on the dopamine (DA) system. While exteroceptive stimuli, such as food and drugs of abuse, are well-established activators of DA-neuron activity, growing evidence indicates that interoceptive signals also play a critical role in modulating reward. Among these, the gut-brain vagal axis has emerged as a key pathway, yet its precise contribution to mesolimbic DA-dependent signaling, dynamics and behaviors remains poorly defined. Here, we combine complementary ex vivo and in vivo approaches across multiple scales to investigate how the gut-brain vagal axis regulates DA dynamics and reward-related behaviors. We show that gut-brain vagal tone is essential for gating mesolimbic DA system activity and functions, modulating DA-dependent molecular and cellular processes, and scaling both food- and drugs-induced reinforcement. These findings challenge the traditional brain-centric view of reward processing, supporting a more unified and integrated model in which gut-derived and vagus-mediated interoceptive signals are pivotal in intrinsically shaping motivation and reinforcement. By uncovering the influence of gut-brain vagal communication on mesolimbic DA functions, this work offers new insights into the neurobiological mechanisms underlying both adaptive and maladaptive reward processes, with broad implications for eating disorders and addiction.

neuroscience↗

bioRxiv2024

A novel critic signal in identified midbrain dopaminergic neurons of mice training inoperant tasks

Classically, midbrain dopaminergic neuron activity is triggered by unexpected rewards, then, upon learning, by reward-predictive conditioned stimuli. When expected rewards are withheld, firing is inhibited. This activity occurs too late to directly affect the neuronal circuitry underlying decision-making, inspiring the development of temporal difference (TD) reinforcement learning models. To test for more timely critical feedback during decision-making and learning, we recorded optogenetically identified dopaminergic, putative GABAergic and other neurons of the ventral tegmental area (VTA) and substantia nigra pars compacta in mice training in visual and olfactory discrimination tasks. The mice often adhered to unrewarded and untrained task strategies (e.g., spatial alternation) rather than making random choices. In order to probe for reward/punishment predictive activity, a delay was imposed between nose-poke choices and signals for reward or punishment. As animals performed below criterion levels, dopaminergic and other neurons firing rates signaled correct versus incorrect choices immediately after choices, but prior to the onset of trial outcome signals. Thus, this activity signaled the rewarded rule even as the mice performed other unrewarded strategies. Putative GABAergic neurons fired during nose-poke choices, potentially reducing network activity prior to reward prediction signals. This reward predictive activity could serve as a critic signal expressed immediately after choices are made, priming the network for canonical DA reward/punishment activity, facilitating network functional modifications. This is consistent with a role for dopamine in arbitration between brain modules to choose among diverse strategies during goal-directed behavior. These findings suggest extensions of theoretical formulations interpreting dopaminergic neuronal activity. Significance statementModels of dopaminergic influence on circuit modifications during learning evoke mechanisms dealing with the delay between neural activity leading up to choices, and when the reinforcing outcome actually occurs. Here, as mice trained in sensory discrimination tasks with a delay between behavioral responses and reinforcement signals, they performed several unrewarded behavioral strategies. Simultaneously, dopaminergic nuclei neurons instead reflected the current task rule, predicting whether the choice was correct or not, providing an immediate "critic" signal prior to canonical trial outcome signals. This provides evidence for brain mechanisms to overcome innate or acquired habits to perform behaviors optimizing positive outcomes.

neuroscience↗

bioRxiv2022

Rhythmic oscillations in the midbrain dopaminergic nuclei in mice

Dopamine release in the forebrain by midbrain ventral tegmental nucleus (VTA) and substantia nigra pars compacta (SNpc) neurons is implicated in reward processing, goal-directed learning, and decision-making. Rhythmic oscillations of neural excitability underlie coordination of network processing, and have been reported in these dopaminergic nuclei at several frequency bands. This paper provides a comparative characterization of several frequencies of oscillations of local field potential and single unit activity, highlighting some behavioral correlates. We recorded from optogenetically identified dopaminergic sites in mice training in operant olfactory and visual discrimination tasks. Rayleigh and Pairwise Phase Consistency (PPC) analyses revealed some VTA/SNc neurons phase-locked to each frequency range, with fast spiking interneurons (FSIs) prevalent at 1-2.5 Hz (slow) and 4 Hz bands, and dopaminergic neurons predominant in the theta band. More FSIs than dopaminergic neurons were phase-locked in the slow and 4 Hz bands during many task events. The highest incidence of phase-locking in neurons was in the slow and 4 Hz bands, and occurred during the delay between the operant choice and trial outcome (reward or punishment) signals. These data provide a basis for further examination of rhythmic coordination of activity of dopaminergic nuclei with other brain structures, and its impact for adaptive behavior.

neuroscience↗

bioRxiv2018

Opto-activation of cortical somatostatin interneurons alleviates parkinsonian symptoms

Deep brain stimulation of the subthalamic nucleus is a symptomatic treatment of Parkinsons disease but benefits only to a minority of patients due to stringent eligibility criteria. To investigate new targets for less invasive therapies, we aimed at elucidating key mechanisms supporting deep brain stimulation efficiency. Here, using in vivo electrophysiology, optogenetics and modeling, we found that subthalamic stimulation normalizes pathological hyperactivity of motor cortex pyramidal cells, while concurrently activating somatostatin and inhibiting parvalbumin interneurons. In vivo opto-activation of cortical somatostatin interneurons alleviates motor symptoms in a parkinsonian mouse model. A mathematical model highlights how the decrease in pyramidal neurons activity can restore information processing capabilities. Overall, these results demonstrate that activation of cortical somatostatin interneurons may constitute a less invasive alternative than subthalamic stimulation.\n\nOne-sentence SummaryDeep brain stimulation recruits cortical somatostatin interneurons, and their opto-activation is beneficial in Parkinsons.

neuroscience↗