Classical studies of attention have identified areas of parietal and frontal cortex as sources of attentional control. Recently, a ventral region in the macaque temporal cortex, the posterior infero-temporal dorsal area PITd, has been suggested as a third attentional control area. This raises the question of whether and how spatially distant areas coordinate a joint focus of attention. Here we tested the hypothesis that parieto-frontal attention areas and PITd are directly interconnected. By combining functional MRI with ex-vivo high-resolution diffusion MRI, we found that PITd and dorsal attention areas are all directly connected through three specific fascicles. These results ascribe a new function, the communication of attention signals, to two known fiber-bundles, highlight the importance of vertical interactions across the two visual streams, and imply that the control of endogenous attention, hitherto thought to reside in macaque dorsal cortical areas, is exerted by a dorso-ventral network.
All data generated or analysed during this study are included in the manuscript and supporting files. Source data for Figures 2, 3, 4, 5, have been made available via the Open Science Framework (https://osf.io/8ks5t/).
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: Our Protocols protocol has been approved by The Rockefeller University, Institutional Animal Care and Use Committee. In vivo imaging procedures were performed at the Center for Advanced Imaging of Bremen University. They conformed to the National Institutes of Health Guide for Use and Care of Laboratory Animals, regulations for the welfare of experimental animals issued by the federal government of Germany,and stipulations of local Bremen authorities
© 2019, Sani et al.
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Preclinical and clinical studies show that mild to moderate hypothermia is neuroprotective in sudden cardiac arrest, ischemic stroke, perinatal hypoxia/ischemia, traumatic brain injury, and seizures. Induction of hypothermia largely involves physical cooling therapies, which induce several clinical complications, while some molecules have shown to be efficient in pharmacologically induced hypothermia (PIH). Neurotensin (NT), a 13 amino acid neuropeptide that regulates body temperature, interacts with various receptors to mediate its peripheral and central effects. NT induces PIH when administered intracerebrally. However, these effects are not observed if NT is administered peripherally, due to its rapid degradation and poor passage of the blood-brain barrier (BBB). We conjugated NT to peptides that bind the low-density lipoprotein receptor (LDLR) to generate ‘vectorized’ forms of NT with enhanced BBB permeability. We evaluated their effects in epileptic conditions following peripheral administration. One of these conjugates, VH-N412, displayed improved stability, binding potential to both the LDLR and NTSR-1, rodent/human cross-reactivity and improved brain distribution. In a mouse model of kainate (KA)-induced status epilepticus (SE), VH-N412 elicited rapid hypothermia associated with anticonvulsant effects, potent neuroprotection, and reduced hippocampal inflammation. VH-N412 also reduced sprouting of the dentate gyrus mossy fibers and preserved learning and memory skills in the treated mice. In cultured hippocampal neurons, VH-N412 displayed temperature-independent neuroprotective properties. To the best of our knowledge, this is the first report describing the successful treatment of SE with PIH. In all, our results show that vectorized NT may elicit different neuroprotection mechanisms mediated by hypothermia and/or by intrinsic neuroprotective properties.
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