In the context of HPC platforms, individual nodes nowadays consist in heterogenous processing resources such as GPU units and multicores. Those resources share communication and storage resources, inducing complex co-scheduling effects, and making it hard to predict the exact duration of a task or of a communication. To cope with these issues, runtime dynamic schedulers such as StarPU have been developed. These systems base their decisions at runtime on the state of the platform and possibly on static priorities of tasks computed offline. In this paper, our goal is to quantify performance variability in the context of HPC heterogeneous nodes, by focusing on very regular dense linear algebra kernels. Then, we analyze the impact of this variability on a dynamic runtime scheduler such as StarPU, in order to analyze whether the strategies that have been designed in the context of MapReduce applications to cope with stragglers could be transferred to HPC systems, or if the dynamic nature of runtime schedulers is enough to cope with actual performance variations.

Our recent study demonstrated the critical role of the mesolimbic dopamine (DA) circuit and its brain-derived neurotropic factor (BDNF) signaling in mediating neuropathic pain. The present study aims to investigate the functional role of GABA-ergic inputs from the lateral hypothalamus to the ventral tegmental area (LHGABA→VTA) in regulating the mesolimbic DA circuit and its BDNF signaling underlying physiological and pathological pain. We demonstrated that optogenetic manipulation of the LHGABA→VTA projection bi-directionally regulated pain sensation in naïve male mice. Optogenetic inhibition of this projection generated an analgesic effect in mice with pathological pain induced by chronic constrictive injury (CCI) of the sciatic nerve and persistent inflammatory pain by Complete Freund's Adjuvant. Trans-synaptic viral tracing revealed a monosynaptic connection between LH GABA-ergic neurons and VTA GABA-ergic neurons. Functionally,in vivocalcium/neurotransmitter imaging showed an increased DA neuronal activity, decreased GABA-ergic neuronal activity in the VTA, and increased dopamine release in the NAc, in response to optogenetic activation of the LHGABA→VTA projection. Furthermore, repeated activation of the LHGABA→VTA projection was sufficient to increase the expression of mesolimbic BDNF protein, an effect seen in mice with neuropathic pain. Inhibition of this circuit induced a decrease in mesolimbic BDNF expression in CCI mice. Interestingly, the pain behaviors induced by activation of the LHGABA→VTA projection could be prevented by pretreatment with intra-NAc administration of ANA-12, a TrkB receptor antagonist. These results demonstrated that LHGABA→VTA projection regulated pain sensation by targeting local GABA-ergic interneurons to disinhibit the mesolimbic DA circuit and regulating accumbal BDNF release.Significance StatementThe mesolimbic dopamine (DA) system its brain-derived neurotropic factor (BDNF) signaling has been implicated in pain regulation, however, underlying mechanisms remain poorly understood. The lateral hypothalamus (LH) sends the different afferent fibers into and strongly influences function of mesolimbic DA system. Here, utilizing cell type- and projection-specific viral tracing, optogenetics, in vivo calcium and neurotransmitter imaging, our current study identified the LHGABA-VTA projection as a novel neural circuit for pain regulation, possibly by targeting the VTA GABA-ergic neurons to disinhibit mesolimbic pathway-specific DA release and BDNF signaling. This study provides a better understanding of the role of LH and the mesolimbic DA system in physiological and pathological pain.

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