The hippocampus’s dorsal and ventral parts are involved in different operative circuits, the functions of which vary in time during the night and day cycle. These functions are altered in epilepsy. Since energy production is tailored to function, we hypothesized that energy production would be space- and time-dependent in the hippocampus and that such an organizing principle would be modified in epilepsy. Using metabolic imaging and metabolite sensing ex vivo, we show that the ventral hippocampus favors aerobic glycolysis over oxidative phosphorylation as compared to the dorsal part in the morning in control mice. In the afternoon, aerobic glycolysis is decreased and oxidative phosphorylation increased. In the dorsal hippocampus, the metabolic activity varies less between these two times but is weaker than in the ventral. Thus, the energy metabolism is different along the dorsoventral axis and changes as a function of time in control mice. In an experimental model of epilepsy, we find a large alteration of such spatiotemporal organization. In addition to a general hypometabolic state, the dorsoventral difference disappears in the morning, when seizure probability is low. In the afternoon, when seizure probability is high, the aerobic glycolysis is enhanced in both parts, the increase being stronger in the ventral area. We suggest that energy metabolism is tailored to the functions performed by brain networks, which vary over time. In pathological conditions, the alterations of these general rules may contribute to network dysfunctions.
Primary cilia (PC) are microtubule-based protrusions of the cell membrane transducing molecular signals during brain development. Here, we report that PC are required for maintenance of Substantia nigra (SN) dopaminergic (DA) neurons highly vulnerable in Parkinson’s disease (PD). Targeted blockage of ciliogenesis in differentiated DA neurons impaired striato-nigral integrity in adult mice. The relative number of SN DA neurons displaying a typical auto-inhibition of spontaneous activity in response to dopamine was elevated under control metabolic conditions, but not under metabolic stress. Strikingly, in the absence of PC, the remaining SN DA neurons were less vulnerable to the PD neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP). Our data indicate conserved PC-dependent neuroadaptive responses to DA lesions in the striatum. Moreover, PC control the integrity and dopamine response of a subtype of SN DA neurons. These results reinforce the critical role of PC as sensors of metabolic stress in PD and other disorders of the dopamine system.
Energy production, mostly via glycolysis and oxidative phosphorylation, which is at the core of cell function, varies in a circadian manner. Whether energy production is tailored to the functional needs of the networks remains poorly understood. The dorsal and ventral part of the hippocampus are involved in different functional circuits. Using metabolic imaging and metabolite sensing, we show that the ventral hippocampus favors aerobic glycolysis over oxidative phosphorylation as compared to the dorsal part in the morning. However, in the afternoon, aerobic glycolysis is decreased and oxidative phosphorylation increased in the ventral hippocampus. In the dorsal hippocampus, the metabolic activity varies less between these two times but is still weaker than in the ventral. Thus, energy metabolism is different in space (along the dorso-ventral axis) and time (in a circadian manner) in the hippocampus. A similar analysis in an experimental model of epilepsy revealed a large alteration of such spatio-temporal organization. In addition to a general hypometabolic state, the spatial difference disappeared in the morning, when seizure probability is low. In the afternoon, when seizure probability is high, the aerobic glycolysis was enhanced in both parts but this increase was stronger in the ventral area. We suggest that energy metabolism is tailored to the functions performed by brain networks, which vary in space and time. In pathological conditions, the alterations of these general rules may contribute to network dysfunctions. *
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