Search bioRxiv⌕ Search

Biology subjects

Costa, R. M.

Publications and source records attributed to Costa, R. M..

41 records · Page 3Linked to original sources

SUSTAINED DOPAMINERGIC PLATEAUS AND NORADRENERGIC DEPRESSIONS BIAS TRANSITIONS INTO EXPLOITATIVE BEHAVIORAL STATES

We are constantly faced with the trade-off between exploiting actions with known outcomes and exploring alternative actions whose outcomes may be better. This balance has been hypothesized to rely on dopaminergic neurons of the substantia nigra pars compacta (SNc)1 and noradrenergic neurons of the locus coeruleus (LC)2-3. We developed a behavioral paradigm to capture exploitative and exploratory states, and imaged calcium dynamics in genetically-identified dopaminergic SNc neurons and noradrenergic LC neurons during state transitions. During exploitative states, characterized by motivated repetition of the same action choice, we found dichotomous changes in baseline activity in SNc and LC, with SNc showing higher and LC showing lower sustained activity. These sustained neural states emerged from the accumulation of lengthened positive responses and hysteretic dynamics in SNc networks, and lengthened negative responses in LC. Sustained activity could not be explained by classical reinforcement learning parameters, and in SNc but not LC, emerged in subpopulations coding for response vigor. Manipulating the sustained activity of SNc and LC revealed that dopaminergic activity primarily mediates engagement and motivation, whereas noradrenergic activity modulates action selection. These data uncover the emergence of sustained neural states in dopaminergic and noradrenergic networks that mediate dissociable aspects of exploitative bouts.

neuroscience↗

An amygdala circuit mediates experience-dependent momentary exploratory arrests

Exploration of novel environments ensures survival and evolutionary fitness. This behavior is expressed through exploratory bouts and arrests, which change dynamically based on experience. Neural circuits mediating exploratory behavior should therefore integrate experience and use it to select the proper behavioral output. Using a spatial exploration assay, we uncovered an experience-dependent increase of momentary arrests in visited locations where animals previously arrested. Quantitative analyses of neuronal calcium activity in freely-exploring mice revealed that a large neuronal ensemble in basolateral amygdala is active during self-paced behavioral arrests. This ensemble was recruited in an experience-dependent manner, and closed-loop optogenetic manipulation of these neurons revealed that they are sufficient and necessary to drive experience-dependent arrests. Additionally, we found that neurons in the basolateral amygdala projecting to central amygdala mediate these momentary arrests. These findings uncover an amygdala circuit that mediates momentary exploratory arrests in familiar places, without changing place preference or anxiety/fear-like behaviors.

neuroscience↗

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↗

Right-sided brain lesions predominate among patients with lesional mania: evidence from a systematic review and pooled lesion analysis

BackgroundDespite claims that lesional mania is associated with right-hemisphere lesions, supporting evidence is scarce, and association with specific brain areas has not been demonstrated.\n\nAimsTo test whether focal brain lesions in lesional mania are more often right-than left-sided, and if lesions converge on areas relevant to mood regulation.\n\nMethodsWe performed a systematic literature search (PROSPERO registration CRD42016053675) on PubMed and Web-Of-Science, using terms that reflected diagnoses and structures of interest, and lesional mechanisms. Two researchers reviewed the articles separately according to PRISMA Guidelines, to select reports of adult-onset hypomania, mania or mixed state following a focal brain lesion. When available, eligible lesion images were manually traced onto the corresponding slices of MNI space, and lesion topography analyzed using standard brain atlases. Pooled-analyses of individual patient data were performed.\n\nResultsData from 207 lesional mania patients was extracted from 110 reports. Among patients with focal lesions (N=197) more patients had lesions involving the right (84.3%) than the left (34.5%) hemisphere. Among 54 lesion images that were available, right-sided predominance of lesions was confirmed, and found to be was conserved across multiple brain regions, including the temporal lobe, fusiform gyrus and thalamus. These, in addition to several frontal lobe areas, were also identified as preferential lesion sites in comparisons with control lesions.\n\nConclusionsPooled-analyses, based on the most comprehensive dataset of lesional mania available to date, confirm a preferential association with right-hemisphere lesions, while suggesting that several brain areas/circuits, relevant to mood regulation, are most frequently affected.

neuroscience↗

Single-Trial Inhibition of Anterior Cingulate Disrupts Model-based Reinforcement Learning in a Two-step Decision Task.

The anterior cingulate cortex (ACC) is implicated in learning the value of actions, but it remains poorly understood whether and how it contributes to model-based mechanisms that use action-state predictions and afford behavioural flexibility. To isolate these mechanisms, we developed a multi-step decision task for mice in which both action-state transition probabilities and reward probabilities changed over time. Calcium imaging revealed ramps of choice-selective neuronal activity, followed by an evolving representation of the state reached and trial outcome, with different neuronal populations representing reward in different states. ACC neurons represented the current action-state transition structure, whether state transitions were expected or surprising, and the predicted state given chosen action. Optogenetic inhibition of ACC blocked the influence of action-state transitions on subsequent choice, without affecting the influence of rewards. These data support a role for ACC in model-based reinforcement learning, specifically in using action-state transitions to guide subsequent choice. HighlightsO_LIA novel two-step task disambiguates model-based and model-free RL in mice. C_LIO_LIACC represents all trial events, reward representation is contextualised by state. C_LIO_LIACC represents action-state transition structure, predicted states, and surprise. C_LIO_LIInhibiting ACC impedes action-state transitions from influencing subsequent choice. C_LI

neuroscience↗