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Barrot, M.

Publications and source records attributed to Barrot, M..

3 recordsLinked to original sources

tVTA controls dual dopaminergic inputs to the external Globus Pallidus

Midbrain dopamine (DA) neurons critically regulate basal ganglia function through their widespread projections. While the nigrostriatal pathway is well characterized and represents the dominant source of DA in the basal ganglia, other nuclei such as the external Globus Pallidus (GPe) also receive dopaminergic innervation, yet no consensus exists about its precise anatomical origin. In addition, the GABAergic tail of the ventral tegmental area (tVTA) provides a major inhibitory input to midbrain DA neurons, but its influence over DA pathways to the GPe remains unknown. In the rat, we combined retrograde tracing, immunohistochemistry, and ex vivo electrophysiology to identify distinct populations of DA neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) that project to the GPe and display distinct electrophysiological properties. Using optogenetics and electrophysiology, we also demonstrate that these GPe-projecting DA neurons receive powerful inhibitory input from the tVTA. Together, our findings define both the origin and inhibitory control of dopaminergic innervation to the GPe, revealing a previously unrecognized disynaptic circuit (tVTA[->]DA[->]GPe) that refines our understanding of basal ganglia circuit function.

neuroscience↗

The basolateral amygdala-anterior cingulate pathway contributes to depression and its comorbidity with chronic pain

While depression and chronic pain are frequently comorbid, underlying neuronal circuits, and their relevance for the understanding of psychopathology, remain poorly defined. Here we show in mice that hyperactivity of the neuronal pathway linking the basolateral amygdala to the anterior cingulate cortex is essential for chronic pain-induced depression. In naive animals, we demonstrate that activation of this pathway is sufficient to trigger depressive-like behaviors, as well as transcriptomic alterations that recapitulate core molecular features of depression in the human brain. These alterations notably impact gene modules related to myelination and the oligodendrocyte lineage. Among these, we show that Sema4a, a hub gene significantly upregulated in both mice and humans in the context of altered mood, is necessary for the emergence of depressive-like behaviors. Overall, these results place the BLA-ACC pathway at the core of pain and depression comorbidity, and unravel the role of impaired myelination and Sema4a in mood control.

neuroscience↗

Midbrain and lateral nucleus accumbens dopamine depletion affects free-choice high-fat high-sugar diet preference in male rats

Dopamine influences food intake behavior. Reciprocally, food intake, especially of palatable dietary items, can modulate dopamine-related brain circuitries. Among these reciprocal impacts, it has been observed that an increased intake of dietary fat results in blunted dopamine signaling and, to compensate this lowered dopamine function, caloric intake may subsequently increase. To determine how dopamine regulates food preference we did 6-hydroxydopamine (6-OHDA) lesions, depleting dopamine in specific brain regions in male Sprague Dawley rats. The food preference was assessed by providing the rats with free choice access to control diet, fat, 20% sucrose and tap water. Rats with midbrain lesions targeting the substantia nigra (which is also a model of Parkinsons disease) consumed fewer calories, as reflected by a decrease in control diet intake, but they surprisingly displayed an increase in fat intake, without change in the sucrose solution intake compared to sham animals. To determine which of the midbrain dopamine projections may contribute to this effect, we next compared the impact of 6-OHDA lesions of terminal fields, targeting the dorsal striatum, the lateral nucleus accumbens and the medial nucleus accumbens. We found that 6-OHDA lesion of the lateral nucleus accumbens, but not of the dorsal striatum or the medial nucleus accumbens, led to increased fat intake. These findings indicate a role for lateral nucleus accumbens dopamine in regulating food preference, in particularly the intake of fat. HIGHLIGHTSO_LIDopamine influences fat intake C_LIO_LIAnimal model of Parkinsons disease display lower kcal intake but increased fat choice C_LIO_LIDopamine depletion in the lateral nucleus accumbens favors fat intake C_LI

neuroscience↗