Biology subjects

Alves da Silva, J.

Publications and source records attributed to Alves da Silva, J..

3 recordsLinked to original sources

bioRxiv2022

Dynamic refinement of behavioral structure mediates dopamine-dependent credit assignment

Animals exhibit a diverse behavioral repertoire when exploring new environments and can learn which actions or action sequences produce positive outcomes. Dopamine release upon encountering reward is critical for reinforcing reward-producing actions1-3. However, it has been challenging to understand how credit is assigned to the exact action that produced dopamine release during continuous behavior. We investigated this problem with a novel self-stimulation paradigm in which specific spontaneous movements triggered optogenetic stimulation of dopaminergic neurons. Dopamine self-stimulation rapidly and dynamically changes the structure of the entire behavioral repertoire. Initial stimulations reinforced not only the stimulation-producing target action, but also actions similar to target and actions that occurred a few seconds before stimulation. Repeated pairings led to gradual refinement of the behavioral repertoire to home in on the target. Reinforcement of action sequences revealed further temporal dependencies of refinement. Action pairs spontaneously separated by long time intervals promoted a stepwise credit assignment, with early refinement of actions most proximal to stimulation and subsequent refinement of more distal actions. Thus, a retrospective reinforcement mechanism promotes not only reinforcement, but gradual refinement of the entire behavioral repertoire to assign credit to specific actions and action sequences that lead to dopamine release.

neuroscience↗

bioRxiv2021

Transient dopamine neuron activity precedes and encodes the vigor of contralateral movements

Dopamine neurons (DANs) in the substantia nigra pars compacta (SNc) have been related to movement vigor, and loss of these neurons leads to bradykinesia in Parkinsons disease. However, it remains unclear whether DANs encode a general motivation signal or modulate movement kinematics. We imaged activity of SNc DANs in mice trained in a novel operant task which relies on individual forelimb sequences. We uncovered that a similar proportion of SNc DANs increased their activity before ipsi- vs. contralateral sequences. However, the magnitude of this activity was higher for contralateral actions, and was related to contralateral but not ipsilateral sequence length. In contrast, the activity of reward-related DANs, largely distinct from those modulated by movement, was not lateralized. Finally, unilateral dopamine depletion impaired contralateral, but not ipsilateral, sequence length. These results indicate that movement-initiation DANs encode more than a general motivation signal, and invigorate kinematic aspects of contralateral movements. TeaserTransient activity in substantia nigra compacta dopamine neurons encodes contralateral, but not ipsilateral action vigor.

neuroscience↗

bioRxiv2019

Light-entrained and brain-tuned circadian circuits regulate ILC3 and gut homeostasis

Group 3 innate lymphoid cells (ILC3) are major regulators of inflammation, infection, microbiota composition and metabolism1. ILC3 and neuronal cells were shown to interact at discrete mucosal locations to steer mucosal defence2,3. Nevertheless, whether neuroimmune circuits operate at an organismal level, integrating extrinsic environmental signals to orchestrate ILC3 responses remains elusive. Here we show that light-entrained and brain-tuned circadian circuits regulate enteric ILC3, intestinal homeostasis, gut defence and the host lipid metabolism. We found that enteric ILC3 display circadian expression of clock genes and ILC3-related transcription factors. ILC3-autonomous ablation of the circadian regulator Arntl led to disrupted gut ILC3 homeostasis, impaired epithelial reactivity, deregulated microbiome, increased susceptibility to bowel infection and disrupted lipid metabolism. Loss of ILC3-intrinsic Arntl shaped the gut postcode receptors of ILC3. Strikingly, light-dark cycles, feeding rhythms and microbial cues differentially regulated ILC3 clocks, with light signals as major entraining cues of ILC3. Accordingly, surgical- and genetically-induced deregulation of brain rhythmicity led to disrupted circadian ILC3 oscillations, deregulated microbiome and altered lipid metabolism. Our work reveals a circadian circuitry that translates environmental light cues into enteric ILC3, shaping intestinal health, metabolism and organismal homeostasis.

immunology↗