Efficacy of nonselective optogenetic control of the medial septum over hippocampal oscillations: the influence of speed and implications for cognitive enhancement

Optogenetics holds great promise for both the dissection of neural circuits and the evaluation of theories centered on the temporal organizing properties of oscillations that underpin cognition. To date, no studies have examined the efficacy of optogenetic stimulation for altering hippocampal oscillations in freely moving wild-type rats, or how these alterations would affect performance on behavioral tasks. Here, we used an AAV virus to express ChR2 in the medial septum (MS) of wild-type rats, and optically stimulated septal neurons at 6 Hz and 30 Hz. We measured the corresponding effects of these stimulations on the oscillations of the MS and hippocampal subfields CA1 and CA3 in three different contexts: (1) With minimal movement while the rats sat in a confined chamber; (2) Explored a novel open field; and (3) Learned and performed a T-maze behavioral task. While control yellow light stimulation did not affect oscillations, 6-Hz blue light septal stimulations altered hippocampal theta oscillations in a manner that depended on the animal's mobility and speed. While the 30 Hz blue light septal stimulations only altered theta frequency in CA1 while the rat had limited mobility, it robustly increased the amplitude of hippocampal signals at 30 Hz in both regions in all three recording contexts. We found that animals were more likely to make a correct choice during Day 1 of T-maze training during both MS stimulation protocols than during control stimulation, and that improved performance was independent of theta frequency alterations

Changing the size of a mirror-reflected hand moderates the experience of embodiment but not proprioceptive drift: a repeated measures study on healthy human participants.

Mirror visual feedback is used for reducing pain and visually distorting the size of the reflection may improve efficacy. The findings of studies investigating size distortion are inconsistent. The influence of the size of the reflected hand on embodiment of the mirror reflection is not known. The aim of this study was to compare the effect of magnifying and minifying mirror reflections of the hand on embodiment measured using an eight-item questionnaire and on proprioceptive drift. During the experiment, participants (n = 45) placed their right hand behind a mirror and their left hand in front of a mirror. Participants watched a normal-sized, a magnified and a minified reflection of the left hand while performing synchronised finger movements for 3 min (adaptive phase). Measurements of embodiment were taken before (pre) and after (post) synchronous movements of the fingers of both hands (embodiment adaptive phase). Results revealed larger proprioceptive drift post-adaptive phase (p = 0.001). Participants agreed more strongly with questionnaire items associated with location, ownership and agency of the reflection of the hand post-adaptive phase (p < 0.001) and when looking at the normal-sized reflection (p < 0.001). In conclusion, irrespective of size, watching a reflection of the hand while performing synchronised movements enhances the embodiment of the reflection of the hand. Magnifying and minifying the reflection of the hand has little effect on proprioceptive drift, but it weakens the subjective embodiment experience. Such factors need to be taken into account in future studies using this technique, particularly when assessing mirror visual feedback for pain management

James Hutton’s geological tours of Scotland : romanticism, literary strategies, and the scientific quest

This article explores a somewhat neglected part of the story of the emergence of geology as a science and discourse in the late eighteenth century – James Hutton’s posthumously published accounts of the geological tours of Scotland that he undertook in the years 1785 to 1788 in search of empirical evidence in support of his theory of the Earth and that he intended to include in the projected third volume of his Theory of the Earth of 1795. The article brings some of the assumptions and techniques of literary criticism to bear on Hutton’s scientific travel writing in order to open up new connections between geology, Romantic aesthetics and eighteenth-century travel writing about Scotland. Close analysis of Hutton’s accounts of his field trips to Glen Tilt, Galloway and Arran, supplemented by later accounts of the discoveries at Jedburgh and Siccar Point, reveals the interplay between desire, travel and the scientific quest and foregrounds the textual strategies that Hutton uses to persuade his readers that they share in the experience of geological discovery and interpretation as ‘virtual witnesses’. As well as allowing us to revisit the interrelation between scientific theory and discovery, this article concludes that Hutton was a much better writer than he has been given credit for and suggests that if these geological tours had been published in 1795 they would have made it impossible for critics to dismiss him as an armchair geologist

Functional Network Changes in Hippocampal CA1 after Status Epilepticus Predict Spatial Memory Deficits in Rats

Status epilepticus (SE) is a common neurological emergency, which has been associated with subsequent cognitive impairments. Neuronal death in hippocampal CA1 is thought to be an important mechanism of these impairments. However, it is also possible that functional interactions between surviving neurons are important. In this study we recorded in vivo single-unit activity in the CA1 hippocampal region of rats while they performed a spatial memory task. From these data we constructed functional networks describing pyramidal cell interactions. To build the networks, we used maximum entropy algorithms previously applied only to in vitro data. We show that several months following SE pyramidal neurons display excessive neuronal synchrony and less neuronal reactivation during rest compared with those in healthy controls. Both effects predict rat performance in a spatial memory task. These results provide a physiological mechanism for SE-induced cognitive impairment and highlight the importance of the systems-level perspective in investigating spatial cognition

Discovery of mating in the major African livestock pathogen Trypanosoma congolense

The protozoan parasite, Trypanosoma congolense, is one of the most economically important pathogens of livestock in Africa and, through its impact on cattle health and productivity, has a significant effect on human health and well being. Despite the importance of this parasite our knowledge of some of the fundamental biological processes is limited. For example, it is unknown whether mating takes place. In this paper we have taken a population genetics based approach to address this question. The availability of genome sequence of the parasite allowed us to identify polymorphic microsatellite markers, which were used to genotype T. congolense isolates from livestock in a discrete geographical area of The Gambia. The data showed a high level of diversity with a large number of distinct genotypes, but a deficit in heterozygotes. Further analysis identified cryptic genetic subdivision into four sub-populations. In one of these, parasite genotypic diversity could only be explained by the occurrence of frequent mating in T. congolense. These data are completely inconsistent with previous suggestions that the parasite expands asexually in the absence of mating. The discovery of mating in this species of trypanosome has significant consequences for the spread of critical traits, such as drug resistance, as well as for fundamental aspects of the biology and epidemiology of this neglected but economically important pathogen

The role of the right temporoparietal junction in perceptual conflict: detection or resolution?

The right temporoparietal junction (rTPJ) is a polysensory cortical area that plays a key role in perception and awareness. Neuroimaging evidence shows activation of rTPJ in intersensory and sensorimotor conflict situations, but it remains unclear whether this activity reflects detection or resolution of such conflicts. To address this question, we manipulated the relationship between touch and vision using the so-called mirror-box illusion. Participants' hands lay on either side of a mirror, which occluded their left hand and reflected their right hand, but created the illusion that they were looking directly at their left hand. The experimenter simultaneously touched either the middle (D3) or the ring finger (D4) of each hand. Participants judged, which finger was touched on their occluded left hand. The visual stimulus corresponding to the touch on the right hand was therefore either congruent (same finger as touch) or incongruent (different finger from touch) with the task-relevant touch on the left hand. Single-pulse transcranial magnetic stimulation (TMS) was delivered to the rTPJ immediately after touch. Accuracy in localizing the left touch was worse for D4 than for D3, particularly when visual stimulation was incongruent. However, following TMS, accuracy improved selectively for D4 in incongruent trials, suggesting that the effects of the conflicting visual information were reduced. These findings suggest a role of rTPJ in detecting, rather than resolving, intersensory conflict

Phenomenological Implications of Deflected Mirage Mediation: Comparison with Mirage Mediation

We compare the collider phenomenology of mirage mediation and deflected mirage mediation, which are two recently proposed "mixed" supersymmetry breaking scenarios motivated from string compactifications. The scenarios differ in that deflected mirage mediation includes contributions from gauge mediation in addition to the contributions from gravity mediation and anomaly mediation also present in mirage mediation. The threshold effects from gauge mediation can drastically alter the low energy spectrum from that of pure mirage mediation models, resulting in some cases in a squeezed gaugino spectrum and a gluino that is much lighter than other colored superpartners. We provide several benchmark deflected mirage mediation models and construct model lines as a function of the gauge mediation contributions, and discuss their discovery potential at the LHC.Comment: 29 pages, 9 figure

Role of A Novel Angiogenesis FKBPL-CD44 Pathway in Preeclampsia Risk Stratification and Mesenchymal Stem Cell Treatment.

ContextPreeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies.ObjectiveTo investigate the diagnostic and therapeutic target potential of the angiogenesis proteins, FK506-binding protein like (FKBPL) and CD44.Design and interventionFKBPL and CD44 plasma concentration or placental expression were determined in women pre- or postdiagnosis of preeclampsia. Trophoblast and endothelial cell function was assessed following mesenchymal stem cell (MSC) treatment and in the context of FKBPL signaling.Settings and participantsHuman samples prediagnosis (15 and 20 weeks of gestation; n ≥ 57), or postdiagnosis (n = 18 for plasma; n = 4 for placenta) of preeclampsia were used to determine FKBPL and CD44 levels, compared to healthy controls. Trophoblast or endothelial cells were exposed to low/high oxygen, and treated with MSC-conditioned media (MSC-CM) or a FKBPL overexpression plasmid.Main outcome measuresPreeclampsia risk stratification and diagnostic potential of FKBPL and CD44 were investigated. MSC treatment effects and FKBPL-CD44 signaling in trophoblast and endothelial cells were assessed.ResultsThe CD44/FKBPL ratio was reduced in placenta and plasma following clinical diagnosis of preeclampsia. At 20 weeks of gestation, a high plasma CD44/FKBPL ratio was independently associated with the 2.3-fold increased risk of preeclampsia (odds ratio = 2.3, 95% confidence interval [CI] 1.03-5.23, P = 0.04). In combination with high mean arterial blood pressure (>82.5 mmHg), the risk further increased to 3.9-fold (95% CI 1.30-11.84, P = 0.016). Both hypoxia and MSC-based therapy inhibited FKBPL-CD44 signaling, enhancing cell angiogenesis.ConclusionsThe FKBPL-CD44 pathway appears to have a central role in the pathogenesis of preeclampsia, showing promising utilities for early diagnostic and therapeutic purposes