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The proposed mechanisms of sleep-dependent memory consolidation involve the overnight regulation of neural activity at both synaptic and whole-network levels. Now, there is a lack of in vivo data in humans elucidating if, and how, sleep and its varied stages balance neural activity, and if such recalibration benefits memory. We combined electrophysiology with in vivo two-photon calcium imaging in rodents as well as intracranial and scalp electroencephalography (EEG) in humans to reveal a key role for non-oscillatory brain activity during rapid eye movement (REM) sleep to mediate sleep-dependent recalibration of neural population dynamics. The extent of this REM sleep recalibration predicted the success of overnight memory consolidation, expressly the modulation of hippocampal-neocortical activity, favoring remembering rather than forgetting. The findings describe a non-oscillatory mechanism how human REM sleep modulates neural population activity to enhance long-term memory.

In the isolated rat middle cerebral artery (MCA) we investigated the role of nitric oxide (NO)/ cGMP in the vasodilatory response to extraluminal acidosis. Acidosis increased vessel diameter from 140 [+ or -] 27 [micro]m (pH 7.4) to 187 [+ or -] 30 [micro]m (pH 7.0, P [is less than] 0.01). NO synthase (NOS) inhibition by [N.sup.[Omega]]-nitro-L-arginine (L-NNA, 10 [micro]M) reduced baseline diameter (103 [+ or -] 20 [micro]m, P [is less than] 0.01) and attenuated response to acidosis (9 [+ or -] 8 [micro]m). Application of the NO-donors 3-morpholinosydnonimine (1 [micro]M) or S-nitroso-N-acetylpenicillamine (1 [micro]M), or of 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP, 100 [micro]M) reestablished pre-L-NNA diameter at pH 7.4 and reversed L-NNA-induced attenuation of the vessel response to acidosis. Restoration of pre-L-NNA diameter (pH 7.4) by papaverine (20 [micro]M) or nimodipine (30 nM) had no effect on the attenuated response to acidosis. Guanylyl cyclase inhibition with 1H-[1,2,4] oxadiazolo [4,3-a]-quinoxalin-1-one (5 [micro]M) or NOS-inhibition with 7-nitroindazole (7-NI, 100 [micro]M) reduced baseline vessel diameter (109 [+ or -] 8 or 127 [+ or -] 11 [micro]m, respectively) and vasodilation to acidosis, and restoration of baseline diameter with 8-BrcGMP (30 [micro]M) completely restored dilation to pH 7.0. Chronic denervation of NOS-containing perivascular nerves in vivo 14 days before artery isolation significantly reduced pH-dependent reactivity in vitro (diameter increase sham: 48 [+ or -] 14 [micro]m, denervated: 14 [+ or -] 8 [micro]m), and 8-BrcGMP (30 [micro]M) restored dilation to pH 7.0 (denervated: 49 [+ or -] 31 [micro]m). Removal of the endothelium did not change vasodilation to acidosis. We conclude that NO, produced by neuronal NOS of perivascular nerves, is a modulator in the pH-dependent vasoreactivity. acidosis; endothelium; isolated cerebral artery; nitric oxide synthase; rat; soluble guanylyl cyclase

Inflammation is a vital process for the injured tissue restoration and one of its hallmarks is inflammatory hyperalgesia. The cyclooxygenase (COX) pathway is strongly related to the inflammatory and painful process. Usually, the COX-1 isoform is described as homeostatic, while COX-2 is characterized as inducible in inflammatory conditions. Although it is well known that neutrophil cells are the first to arrive at the inflamed site and the major source of COX-2 is still unknown, the specific role of neutrophil-derived COX-2 in the pain process is. Thus, in the present study, we demonstrate for the first time that neutrophil-derived COX-2 plays a key role in peripheral inflammatory hyperalgesia. Conditional knockout mice for COX-2 in neutrophils (COX-2 fl/fl: Mrp8cre±) exhibited higher pain sensitivity after carrageenan (CG) injection and long-lasting IL-1β-induced hyperalgesia compared with the control group (COX-2 fl/fl). Also, CG-induced inflammation in COX-2 fl/fl: Mrp8cre± mice showed COX-1 overexpression, and increased neutrophil migration and pro-inflammatory cytokines (e.g., IL-1β and CXCL1). These findings revealed that neutrophil COX-2 has an important role in the regulation of inflammatory hyperalgesia. [ABSTRACT FROM AUTHOR]