Prolonged drought periods over the last four decades increase flood intensity in southern Africa.

In semi-arid sub-Saharan Africa, climate change and the intensification of human activities have altered the hydrological balance and modified the recurrence of extreme hydroclimatic events, such as droughts and floods. The geomorphological heterogeneity of river catchments across the region, the variable human pressure, and the lack of continuous hydroclimatic data preclude the definition of proper mitigation strategies, with a direct effect on the sustainability of rural communities. Here, for the first time in Africa, we characterize hydrological extreme events using a multidisciplinary approach that includes sedimentary data from dams. We focus on the Limpopo River basin to evaluate which factors control flood magnitude since the 1970. Extreme flood events were identified across the basin in 1988-89, 1995-96, 1999-2000, 2003-04, 2010-11, 2013-14 and 2016-17. The statistical analysis of sedimentary flood records revealed a dramatic increase in their magnitude over the studied period. A positive correlation between maximum river flow and antecedent prolonged drought conditions was found in South Africa and Mozambique. Most importantly, since 1980, we observed the likely decoupling of extreme floods from the magnitude of La Niña events, suggesting that the natural interannual variability driven by El Niño-Southern Oscillation (ENSO) has been disrupted by climate changes and human activities.

Quantifying heterogeneity in ecohydrological partitioning in urban green spaces through the integration of empirical and modelling approaches.

Urban green spaces (UGS) can help mitigate hydrological impacts of urbanisation and climate change through precipitation infiltration, evapotranspiration and groundwater recharge. However, there is a need to understand how precipitation is partitioned by contrasting vegetation types in order to target UGS management for specific ecosystem services. We monitored, over one growing season, hydrometeorology, soil moisture, sapflux and isotopic variability of soil water under contrasting vegetation (evergreen shrub, evergreen conifer, grassland, larger and smaller deciduous trees), focussed around a 150-m transect of UGS in northern Scotland. We further used the data to develop a one-dimensional model, calibrated to soil moisture observations (KGE's generally > 0.65), to estimate evapotranspiration and groundwater recharge. Our results evidenced clear inter-site differences, with grassland soils experiencing rapid drying at the start of summer, resulting in more fractionated soil water isotopes. Contrastingly, the larger deciduous site saw gradual drying, whilst deeper sandy upslope soils beneath the evergreen shrub drained rapidly. Soils beneath the denser canopied evergreen conifer were overall least responsive to precipitation. Modelled ecohydrological fluxes showed similar diversity, with median evapotranspiration estimates increasing in the order grassland (193 mm) < evergreen shrub (214 mm) < larger deciduous tree (224 mm) < evergreen conifer tree (265 mm). The evergreen shrub had similar estimated median transpiration totals as the larger deciduous tree (155 mm and 128 mm, respectively), though timing of water uptake was different. Median groundwater recharge was greatest beneath grassland (232 mm) and lowest beneath the evergreen conifer (128 mm). The study showed how integrating observational data and simple modelling can quantify heterogeneities in ecohydrological partitioning and help guide UGS management.

Synapse-Specific Modulation of Synaptic Responses by Brain States in Hippocampal Pathways.

Synaptic changes play a major role in memory processes. Modulation of synaptic responses by brain states remains, however, poorly understood in hippocampal networks, even in basal conditions. We recorded evoked synaptic responses at five hippocampal pathways in freely moving male rats. We showed that, at the perforant path to dentate gyrus (PP-DG) synapse, responses increase during wakefulness compared with sleep. At the Schaffer collaterals to CA1 (SC-CA1) synapse, responses increase during non-REM sleep (NREM) compared with the other states. During REM sleep (REM), responses decreased at the PP-DG and SC-CA1 synapses compared with NREM, while they increased at the fornix to nucleus accumbens synapse (Fx-NAc) during REM compared with the other states. In contrast, responses at the fornix to medial PFC synapse (Fx-PFC) and at the fornix to amygdala synapse (Fx-Amy) were weakly modulated by vigilance states. Extended sleep periods led to synaptic changes at PP-DG and Fx-Amy synapses but not at the other synapses. Synaptic responses were also linked to local oscillations and were highly correlated between Fx-PFC and Fx-NAc but not between Fx-Amy and these synapses. These results reveal synapse-specific modulations that may contribute to memory consolidation during the sleep-wake cycle.SIGNIFICANCE STATEMENT Surprisingly, the cortical network dynamics remains poorly known at the synaptic level. We tested the hypothesis that brain states would modulate synaptic changes in the same way at different cortical connections. To tackle this issue, we implemented an approach to explore the synaptic behavior of five connections upstream and downstream the rat hippocampus. Our study reveals that synaptic responses are modulated in a highly synapse-specific manner by wakefulness and sleep states as well as by local oscillations at these connections. Moreover, we found rapid synaptic changes during wake and sleep transitions as well as synaptic down and upregulations after extended periods of sleep. These synaptic changes are likely related to the mechanisms of sleep-dependent memory consolidation.

Defects in Mouse Cortical Glutamate Uptake Can Be Unveiled In Vivo by a Two-in-One Quantitative Microdialysis.

Extracellular glutamate levels are maintained low by efficient transporters, whose dysfunction can cause neuronal hyperexcitability, excitotoxicity, and neurological disease. While many methods estimate glutamate uptake in vitro/ex vivo, a limited number of techniques address glutamate transport in vivo. Here, we used in vivo microdialysis in a two-in-one approach combining reverse dialysis of isotopic glutamate to measure uptake ability and zero-flow (ZF) methods to quantify extracellular glutamate levels. The complementarity of both techniques is discussed on methodological and anatomical basis. We used a transgenic mouse model of human disease, expressing low levels of the EAAT-2/GLT1 glutamate transporter, to validate our approach in a relevant animal model. As expected, isotopic analysis revealed an overall decrease in glutamate uptake, while the ZF method unveiled higher extracellular glutamate levels in these mice. We propose a sensitive and expedite two-in-one microdialysis approach that is sufficiently robust to reveal significant differences in neurotransmitter uptake and extracellular levels through the analysis of a relatively low number of animals.

Multimodal Imaging with NanoGd Reveals Spatiotemporal Features of Neuroinflammation after Experimental Stroke.

The purpose of this study is to propose and validate a preclinical in vivo magnetic resonance imaging (MRI) tool to monitor neuroinflammation following ischemic stroke, based on injection of a novel multimodal nanoprobe, NanoGd, specifically designed for internalization by phagocytic cells. First, it is verified that NanoGd is efficiently internalized by microglia in vitro. In vivo MRI coupled with intravenous injection of NanoGd in a permanent middle cerebral artery occlusion mouse model results in hypointense signals in the ischemic lesion. In these mice, longitudinal two-photon intravital microscopy shows NanoGd internalization by activated CX3CR1-GFP/+ cells. Ex vivo analysis, including phase contrast imaging with synchrotron X-ray, histochemistry, and transmission electron microscopy corroborate NanoGd accumulation within the ischemic lesion and uptake by immune phagocytic cells. Taken together, these results confirm the potential of NanoGd-enhanced MRI as an imaging biomarker of neuroinflammation at the subacute stage of ischemic stroke. As far as it is known, this work is the first to decipher the working mechanism of MR signals induced by a nanoparticle passively targeted at phagocytic cells by performing intravital microscopy back-to-back with MRI. Furthermore, using a gadolinium-based rather than an iron-based contrast agent raises future perspectives for the development of molecular imaging with emerging computed tomography technologies.

Working and Reference Memory Tasks Trigger Opposed Long-Term Synaptic Changes in the Rat Dentate Gyrus.

Long-term storage of information into memory is supposed to rely on long-term synaptic plasticity processes. The detection of such synaptic changes after training in long-term/reference memory (RM) tasks has yet been scarce, variable and only studied on a short time scale. Short-term or working memory (WM) is largely known to depend on persistent neuronal activity or short-term plasticity. However, processing information into WM could also involve long-term synaptic changes that could be responsible for the erasure/forgetting of items previously stored in WM and acting as proactive interference. In order to study long-term synaptic changes associated with RM or WM, we trained chronically implanted rats in 3 different radial maze tasks: a classical RM task and 2 WM tasks involving different levels of proactive interference. Synaptic responses in the dentate gyrus were recorded during 2 × 24 h in freely moving rats after training. We found that consolidation of long-term information leads first to a delayed synaptic potentiation, occurring 9 h after RM training that is replaced by a synaptic depression once the RM rule is fully acquired. In contrast, optimal information processing into WM triggers a synaptic depression immediately after training and lasting 3 h that could act as a mechanism for interference erasure/forgetting.

Ketamine/xylazine and barbiturates modulate microglial morphology and motility differently in a mouse model.

Microglia, the resident immune cells of the brain, are highly ramified and motile and their morphology is strongly linked to their function. Microglia constantly monitor the brain parenchyma and are crucial for maintaining brain homeostasis and fine-tuning neuronal networks. Besides affecting neurons, anesthetics may have wide-ranging effects mediated by non-neuronal cells and in particular microglia. We thus examined the effect of two commonly used anesthetic agents, ketamine/xylazine and barbiturates, on microglial motility and morphology. A combination of two-photon in vivo imaging and electroencephalography (EEG) recordings in unanesthetized and anesthetized mice as well as automated analysis of ex vivo sections were used to assess morphology and dynamics of microglia. We found that administration of ketamine/xylazine and pentobarbital anesthesia resulted in quite distinct EEG profiles. Both anesthetics reduced microglial motility, but only ketamine/xylazine administration led to reduction of microglial complexity in vivo. The change of cellular dynamics in vivo was associated with a region-dependent reduction of several features of microglial cells ex vivo, such as the complexity index and the ramification length, whereas thiopental altered the size of the cytoplasm. Our results show that anesthetics have considerable effects on neuronal activity and microglial morphodynamics and that barbiturates may be a preferred anesthetic agent for the study of microglial morphology. These findings will undoubtedly raise compelling questions about the functional relevance of anesthetics on microglial cells in neuronal physiology and anesthesia-induced neurotoxicity.

Correction: Differential recordings of local field potential: A genuine tool to quantify functional connectivity.

[This corrects the article DOI: 10.1371/journal.pone.0209001.].

Differential recordings of local field potential: A genuine tool to quantify functional connectivity.

Local field potential (LFP) recording is a very useful electrophysiological method to study brain processes. However, this method is criticized for recording low frequency activity in a large area of extracellular space potentially contaminated by distal activity. Here, we theoretically and experimentally compare ground-referenced (RR) with differential recordings (DR). We analyze electrical activity in the rat cortex with these two methods. Compared with RR, DR reveals the importance of local phasic oscillatory activities and their coherence between cortical areas. Finally, we show that DR provides a more faithful assessment of functional connectivity caused by an increase in the signal to noise ratio, and of the delay in the propagation of information between two cortical structures.

Highly Dynamic Spatiotemporal Organization of Low-Frequency Activities During Behavioral States in the Mouse Cerebral Cortex.

Although low-frequency (LF < 10 Hz) activities have been considered as a hallmark of nonrapid eye movement (NREM) sleep, several studies have recently reported LF activities in the membrane potential of cortical neurons from different areas in awake mice. However, little is known about the spatiotemporal organization of LF activities across cortical areas during wakefulness and to what extent it differs during NREM sleep. We have thus investigated the dynamics of LF activities across cortical areas in awake and sleeping mice using chronic simultaneous local field potential recordings. We found that LF activities had higher amplitude in somatosensory and motor areas during quiet wakefulness and decreased in most areas during active wakefulness, resulting in a global state change that was overall correlated with motor activity. However, we also observed transient desynchronization of cortical states between areas, indicating a more local state regulation. During NREM sleep, LF activities had higher amplitude in all areas but slow-wave activity was only poorly correlated across cortical areas. Despite a maximal amplitude during NREM sleep, the coherence of LF activities between areas that are not directly connected dropped from wakefulness to NREM sleep, potentially reflecting a breakdown of long-range cortical integration associated with loss of consciousness.

Levels of Interference in Long and Short-Term Memory Differentially Modulate Non-REM and REM Sleep.

STUDY OBJECTIVES: It is commonly accepted that sleep is beneficial to memory processes, but it is still unclear if this benefit originates from improved memory consolidation or enhanced information processing. It has thus been proposed that sleep may also promote forgetting of undesirable and non-essential memories, a process required for optimization of cognitive resources. We tested the hypothesis that non-rapid eye movement sleep (NREMS) promotes forgetting of irrelevant information, more specifically when processing information in working memory (WM), while REM sleep (REMS) facilitates the consolidation of important information. METHODS: We recorded sleep patterns of rats trained in a radial maze in three different tasks engaging either the long-term or short-term storage of information, as well as a gradual level of interference. RESULTS: We observed a transient increase in REMS amount on the day the animal learned the rule of a long-term/reference memory task (RM), and, in contrast, a positive correlation between the performance of rats trained in a WM task involving an important processing of interference and the amount of NREMS or slow wave activity. Various oscillatory events were also differentially modulated by the type of training involved. Notably, NREMS spindles and REMS rapid theta increase with RM training, while sharp-wave ripples increase with all types of training. CONCLUSIONS: These results suggest that REMS, but also rapid oscillations occurring during NREMS would be specifically implicated in the long-term memory in RM, whereas NREMS and slow oscillations could be involved in the forgetting of irrelevant information required for WM.

Whisking-Related Changes in Neuronal Firing and Membrane Potential Dynamics in the Somatosensory Thalamus of Awake Mice.

The thalamus transmits sensory information to the neocortex and receives neocortical, subcortical, and neuromodulatory inputs. Despite its obvious importance, surprisingly little is known about thalamic function in awake animals. Here, using intracellular and extracellular recordings in awake head-restrained mice, we investigate membrane potential dynamics and action potential firing in the two major thalamic nuclei related to whisker sensation, the ventral posterior medial nucleus (VPM) and the posterior medial group (Pom), which receive distinct inputs from brainstem and neocortex. We find heterogeneous state-dependent dynamics in both nuclei, with an overall increase in action potential firing during active states. Whisking increased putative lemniscal and corticothalamic excitatory inputs onto VPM and Pom neurons, respectively. A subpopulation of VPM cells fired spikes phase-locked to the whisking cycle during free whisking, and these cells may therefore signal whisker position. Our results suggest differential processing of whisking comparing thalamic nuclei at both sub- and supra-threshold levels.

Integrating petrography, mineralogy and hydrochemistry to constrain the influence and distribution of groundwater contributions to baseflow in poorly productive aquifers: insights from Gortinlieve catchment, Co. Donegal, NW Ireland.

Identifying groundwater contributions to baseflow forms an essential part of surface water body characterisation. The Gortinlieve catchment (5 km(2)) comprises a headwater stream network of the Carrigans River, itself a tributary of the River Foyle, NW Ireland. The bedrock comprises poorly productive metasediments that are characterised by fracture porosity. We present the findings of a multi-disciplinary study that integrates new hydrochemical and mineralogical investigations with existing hydraulic, geophysical and structural data to identify the scales of groundwater flow and the nature of groundwater/bedrock interaction (chemical denudation). At the catchment scale, the development of deep weathering profiles is controlled by NE-SW regional scale fracture zones associated with mountain building during the Grampian orogeny. In-situ chemical denudation of mineral phases is controlled by micro- to meso-scale fractures related to Alpine compression during Palaeocene to Oligocene times. The alteration of primary muscovite, chlorite (clinochlore) and albite along the surfaces of these small-scale fractures has resulted in the precipitation of illite, montmorillonite and illite-montmorillonite clay admixtures. The interconnected but discontinuous nature of these small-scale structures highlights the role of larger scale faults and fissures in the supply and transportation of weathering solutions to/from the sites of mineral weathering. The dissolution of primarily mineral phases releases the major ions Mg, Ca and HCO3 that are shown to subsequently form the chemical makeup of groundwaters. Borehole groundwater and stream baseflow hydrochemical data are used to constrain the depths of groundwater flow pathways influencing the chemistry of surface waters throughout the stream profile. The results show that it is predominantly the lower part of the catchment, which receives inputs from catchment/regional scale groundwater flow, that is found to contribute to the maintenance of annual baseflow levels. This study identifies the importance of deep groundwater in maintaining annual baseflow levels in poorly productive bedrock systems.

A phantom and animal study of temperature changes during fMRI with intracerebral depth electrodes.

BACKGROUND: MRI is routinely used in patients undergoing intracerebral electroencephalography (icEEG) in order to precisely locate the position of intracerebral electrodes. In contrast, fMRI has been considered unsafe due to suspected greater risk of radiofrequency-induced (RF) tissue heating at the vicinity of intracerebral electrodes. We determined the possible temperature change at the tip of such electrodes during fMRI sessions in phantom and animals. METHODS: A human-shaped torso phantom and MRI-compatible intracerebral electrodes approved for icEEG in humans were used to mimic a patient with four intracerebral electrodes (one parasagittal and three coronal). Six rabbits were implanted with one or two coronal electrodes. MRI-induced temperature changes at the tip of electrodes were measured using a fibre-optic thermometer. All experiments were performed on Siemens Sonata 1.5T scanner. RESULTS: For coronally implanted electrodes with wires pulled posteriorly to the magnetic bore, temperature increase recorded during EPI sequences reached a maximum of 0.6°C and 0.9°C in phantom and animals, respectively. These maximal figures were decreased to 0.2°C and 0.5°C, when electrode wires were connected to cables and amplifier. When electrode wires were pulled anteriorly to the magnetic bore, temperature increased up to 1.3°C in both phantom and animals. Greater temperature increases were recorded for the single electrode implanted parasagitally in the phantom. CONCLUSION: Variation of the temperature depends on the electrode and wire position relative to the transmit body coil and orientation of the constant magnetic field (B0). EPI sequence with intracerebral electrodes appears as safe as standard T1 and T2 sequence for implanted electrodes placed perpendicular to the z-axis of the magnetic bore, using a 1.5T MRI system, with the free-end wires moving posteriorly, in phantom and animals.

A functional magnetic resonance imaging study of pathophysiological changes responsible for mirror movements in Parkinson's disease.

Mirror movements correspond to involuntary movements observed in the limb contralateral to the one performing voluntary movement. They can be observed in Parkinson's disease (PD) but their pathophysiology remains unclear. The present study aims at identifying their neural correlates in PD using functional magnetic resonance imaging. Ten control subjects and 14-off drug patients with asymmetrical right-sided PD were included (8 with left-sided mirror movements during right-hand movements, and 6 without mirror movements). Between-group comparisons of BOLD signal were performed during right-hand movements and at rest (p<0.005 uncorrected). The comparison between PD patients with and without mirror movements showed that mirror movements were associated with an overactivation of the insula, precuneus/posterior cingulate cortex bilaterally and of the left inferior frontal cortex and with a deactivation of the right dorsolateral prefrontal cortex, medial prefrontal cortex, and pre-supplementary motor area and occipital cortex. These data suggest that mirror movements in Parkinson's disease are promoted by: 1- a deactivation of the non-mirroring inhibitory network (dorsolateral prefrontal cortex, pre-supplementary motor area); 2- an overactivation of prokinetic areas (notably the insula). The concomitant overactivation of a proactive inhibitory network (including the posterior cingulate cortex and precuneus) could reflect a compensatory inhibition of mirror movements.

Multimodal convergence within the intraparietal sulcus of the macaque monkey.

The parietal cortex is highly multimodal and plays a key role in the processing of objects and actions in space, both in human and nonhuman primates. Despite the accumulated knowledge in both species, we lack the following: (1) a general description of the multisensory convergence in this cortical region to situate sparser lesion and electrophysiological recording studies; and (2) a way to compare and extrapolate monkey data to human results. Here, we use functional magnetic resonance imaging (fMRI) in the monkey to provide a bridge between human and monkey studies. We focus on the intraparietal sulcus (IPS) and specifically probe its involvement in the processing of visual, tactile, and auditory moving stimuli around and toward the face. We describe three major findings: (1) the visual and tactile modalities are strongly represented and activate mostly nonoverlapping sectors within the IPS. The visual domain occupies its posterior two-thirds and the tactile modality its anterior one-third. The auditory modality is much less represented, mostly on the medial IPS bank. (2) Processing of the movement component of sensory stimuli is specific to the fundus of the IPS and coincides with the anatomical definition of monkey ventral intraparietal area (VIP). (3) A cortical sector within VIP processes movement around and toward the face independently of the sensory modality. This amodal representation of movement may be a key component in the construction of peripersonal space. Overall, our observations highlight strong homologies between macaque and human VIP organization.

Correlation of diffusion and metabolic alterations in different clinical forms of multiple sclerosis.

Diffusion tensor imaging (DTI) and MR spectroscopic imaging (MRSI) provide greater sensitivity than conventional MRI to detect diffuse alterations in normal appearing white matter (NAWM) of Multiple Sclerosis (MS) patients with different clinical forms. Therefore, the goal of this study is to combine DTI and MRSI measurements to analyze the relation between diffusion and metabolic markers, T2-weighted lesion load (T2-LL) and the patients clinical status. The sensitivity and specificity of both methods were then compared in terms of MS clinical forms differentiation. MR examination was performed on 71 MS patients (27 relapsing remitting (RR), 26 secondary progressive (SP) and 18 primary progressive (PP)) and 24 control subjects. DTI and MRSI measurements were obtained from two identical regions of interest selected in left and right centrum semioval (CSO) WM. DTI metrics and metabolic contents were significantly altered in MS patients with the exception of N-acetyl-aspartate (NAA) and NAA/Choline (Cho) ratio in RR patients. Significant correlations were observed between diffusion and metabolic measures to various degrees in every MS patients group. Most DTI metrics were significantly correlated with the T2-LL while only NAA/Cr ratio was correlated in RR patients. A comparison analysis of MR methods efficiency demonstrated a better sensitivity/specificity of DTI over MRSI. Nevertheless, NAA/Cr ratio could distinguish all MS and SP patients groups from controls, while NAA/Cho ratio differentiated PP patients from controls. This study demonstrated that diffusivity changes related to microstructural alterations were correlated with metabolic changes and provided a better sensitivity to detect early changes, particularly in RR patients who are more subject to inflammatory processes. In contrast, the better specificity of metabolic ratios to detect axonal damage and demyelination may provide a better index for identification of PP patients.

Density and frequency caudo-rostral gradients of sleep spindles recorded in the human cortex.

STUDY OBJECTIVE: This study aims at providing a quantitative description of intrinsic spindle frequency and density (number of spindles/min) in cortical areas using deep intracerebral recordings in humans. PATIENTS OR PARTICIPANTS: Thirteen patients suffering from pharmaco-resistant focal epilepsy and investigated through deep intracortical EEG in frontal, parietal, temporal, occipital, insular, and limbic cortices including the hippocampus were included. METHODS: Spindle waves were detected from the ongoing EEG during slow wave sleep (SWS) by performing a time-frequency analysis on filtered signals (band-pass filter: 10-16 Hz). Then, spindle intrinsic frequency was determined using a fast Fourier transform, and spindle density (number of spindles per minute) was computed. RESULTS: Firstly, we showed that sleep spindles were recorded in all explored cortical areas, except temporal neocortex. In particular, we observed the presence of spindles during SWS in areas such as the insular cortex, medial parietal cortex, occipital cortex, and cingulate gyrus. Secondly, we demonstrated that both spindle frequency and density smoothly change along the caudo-rostral axis, from fast frequent posterior spindles to slower and less frequent anterior spindles. Thirdly, we identified the presence of spindle frequency oscillations in the hippocampus and the entorhinal cortex. CONCLUSIONS: Spindling activity is widespread among cortical areas, which argues for the fundamental role of spindles in cortical functions. Mechanisms of caudo-rostral gradient modulation in spindle frequency and density may result from a complex interplay of intrinsic properties and extrinsic modulation of thalamocortical and corticothalamic neurons.

Implementation of an absolute brain 1H-MRS quantification method to assess different tissue alterations in multiple sclerosis.

Magnetic resonance spectroscopy has emerged as a sensitive modality to detect early and diffuse alterations in multiple sclerosis. Recently, the hypothesis of neurodegenerative pathogenesis has highlightened the interest for measurement of metabolites concentrations, to gain specificity, in a large brain volume encompassing different tissue alterations. Therefore, we proposed in this paper the implementation of an absolute quantification method based on localized spectroscopy at short (30 ms) and long (135 ms) echo time of a volume including normal appearing white matter, cortical gray matter, and lesions. First, methodological developments were implemented including external calibration, and corrections of phased-array coil sensitivity and cerebrospinal fluid volume contribution. Second, these improvements were validated and optimized using an original methodology based on simulations of brain images with lesions. Finally, metabolic alterations were assessed in 65 patients including 26 relapsing-remitting, 17 primary-progressive (PP), 22 secondary-progressive (SP) patients, and in 23 normal subjects. Results showed increases of choline, creatine, and myo-inositol concentrations in PP and SP patients compared to controls, whereas the concentration of N-acetyl compounds remained constant. The major finding of this study was the identification of Cho concentration and Cho/tNA ratio as putative markers of progressive onset, suggesting interesting perspectives in detection and followup of neurodegenerative processes.

Paradoxical (REM) sleep deprivation causes a large and rapidly reversible decrease in long-term potentiation, synaptic transmission, glutamate receptor protein levels, and ERK/MAPK activation in the dorsal hippocampus.

STUDY OBJECTIVES: It has been shown that wake (W) and slow wave sleep (SWS) modulate synaptic transmission in neocortical projections. However the impact of paradoxical sleep (PS) quantities on synaptic transmission remains unknown. We examined whether PS modulated the excitatory transmission and expression of glutamate receptor subtypes and phosphorylated extracellular signal-regulated kinases (p-ERK1/2). DESIGN: PS deprivation (PSD) was carried out with the multiple platforms method on adult male Sprague-Dawley rats. LTP, late-LTP, and synaptic transmission were studied in the dorsal and ventral hippocampus of controls, 75-h PSD and 150-min PS rebound (PSR). GluR1 and NR1 protein and mRNA expression were evaluated by western blot and real-time PCR. p-ERK1/2 level was quantified by western blot and immunohistochemistry. MEASUREMENT AND RESULTS: PSD decreased synaptic transmission and LTP selectively in dorsal CA1 and PSR rescued these deficits. PSD-induced synaptic modifications in CA1 were associated with a decrease in GluR1, NR1, and p-ERK1/2 levels in dorsal CA1 without change in GluR1 and NR1 mRNA expression. Regression analysis shows that LTP is positively correlated with both PS quantities and SWS episodes duration, whereas synaptic transmission and late-LTP are positively correlated with PS quantities and negatively correlated with SWS quantities. CONCLUSIONS: These findings unveil previously unrecognized roles of PSD on synaptic transmission and LTP in the dorsal, but not in the ventral, hippocampus. The fact that the decrease in protein expression of GluR1 and NR1 was not associated with a change in mRNA expression of these receptors suggests that a sleep-induced modulation of translational mechanisms occurs in dorsal CA1.