263 research outputs found
Recent changes in area and thickness of Torngat Mountain glaciers (northern Labrador, Canada)
The Torngat Mountains National Park, northern Labrador, Canada, contains more
than 120 small glaciers: the only remaining glaciers in continental northeast
North America. These small cirque glaciers exist in a unique topo-climatic
setting, experiencing temperate maritime summer conditions yet very cold and
dry winters, and may provide insights into the deglaciation dynamics of
similar small glaciers in temperate mountain settings. Due to their size and
remote location, very little information exists regarding the health of these
glaciers. Just a single study has been published on the contemporary
glaciology of the Torngat Mountains, focusing on net mass balances from 1981
to 1984. This paper addresses the extent to which glaciologically relevant
climate variables have changed in northern Labrador in concert with
20th-century Arctic warming, and how these changes have affected Torngat Mountain
glaciers. Field surveys and remote-sensing analyses were used to measure
regional glacier area loss of 27 % from 1950 to 2005, substantial rates of
ice surface thinning (up to 6 m yr<sup>−1</sup>) and volume losses at Abraham,
Hidden, and Minaret glaciers, between 2005 and 2011. Glacier mass balances
appear to be controlled by variations in winter precipitation and,
increasingly, by strong summer and autumn atmospheric warming since the
early 1990s, though further observations are required to fully understand
mass balance sensitivities. This study provides the first comprehensive
contemporary assessment of Labrador glaciers and will inform both regional
impact assessments and syntheses of global glacier mass balance
Long- and short-range connectivity and neuronal types affect prefrontal dorsal raphe circuit dynamics differently
In vivo electrophysiological study of the targeting of 5-HT3 receptor-expressing cortical interneurons by the multimodal antidepressant, vortioxetine
This study was supported by an educational grant from H. Lundbeck A/S.The antidepressant vortioxetine has high affinity for the ionotropic 5-HT3 receptor (5-HT3R) as well as other targets including the 5-HT transporter. The procognitive effects of vortioxetine have been linked to altered excitatory:inhibitory balance in cortex. Thus, vortioxetine purportedly inhibits cortical 5-HT3R-expressing interneurons (5-HT3R-INs) to disinhibit excitatory pyramidal neurons. The current study determined for the first time, the effect of vortioxetine on the in vivo firing of putative 5-HT3R-INs whilst simultaneously recording pyramidal neuron activity using cortical slow-wave oscillations as a readout. Extracellular single unit and local field potential recordings were made in superficial layers of the prefrontal cortex of urethane-anaesthetised rats. 5-HT3R-INs were identified by a short-latency excitation evoked by electrical stimulation of the dorsal raphe nucleus (DRN). Juxtacellular-labelling found such neurons had the morphological and immunohistochemical properties of 5-HT3R-INs; basket cell or bipolar cell morphology, expression of 5-HT3R-IN markers, and parvalbumin-immunonegative. Vortioxetine inhibited the short-latency DRN-evoked excitation of 5-HT3R-INs and simultaneously decreased cortical slow wave oscillations, indicative of pyramidal neuron activation. Likewise, the 5-HT3R antagonist ondansetron inhibited the short-latency DRN-evoked excitation of 5-HT3R-INs. However unlike vortioxetine, ondansetron did not decrease cortical slow-wave oscillations suggesting a dissociation between this effect and inhibition of 5-HT3R-INs. The 5-HT reuptake inhibitor escitalopram had no consistent effect on any electrophysiological parameter measured. Overall, the current findings suggest that vortioxetine simultaneously inhibits (DRN-evoked) 5-HT3R-INs and excites pyramidal neurons, thereby changing the excitatory:inhibitory balance in cortex. However, under the current experimental conditions these two effects were dissociable with only the former likely involving a 5-HT3R-mediated mechanism.Publisher PDFPeer reviewe
Decisions to use complementary and alternative medicine (CAM) by male cancer patients: information-seeking roles and types of evidence used
<p>Abstract</p> <p>Background</p> <p>Complementary and Alternative Medicine (CAM) is increasingly popular with cancer patients and yet information provision or discussion about CAM by health professionals remains low. Previous research suggests that patients may fear clinicians' 'disapproval' if they raise the subject of CAM, and turn to other sources to acquire information about CAM. However, little empirical research has been conducted into how cancer patients acquire, and, more importantly evaluate CAM information before deciding which CAM therapies to try.</p> <p>Methods</p> <p>Qualitative study, comprising semi-structured interviews with 43 male cancer patients of varying ages, cancer type and stage of illness, 34 of whom had used CAM. They were recruited from a range of NHS and non-NHS settings in Bristol, England.</p> <p>Results</p> <p>As a result of the lack of CAM information from health professionals, men in this study became either 'pro-active seekers' or 'passive recipients' of such information. Their main information resource was the 'lay referral' network of family, friends and acquaintances, especially females. 'Traditional' information sources, including books, magazines, leaflets and the media were popular, more so in fact than the internet. Views on the internet ranged from enthusiasm or healthy scepticism through to caution or disinterest. CAM information was generally regarded as 'empowering' as it broadened treatment and self-care options. A minority of participants were information averse fearing additional choices that might disrupt their fragile ability to cope. There was general consensus that CAM information should be available via the NHS, to give it a 'stamp of approval', which combined with guidance from informed health professionals, could help patients to make 'guided' choices. However, a small minority of these men valued the independence of CAM from the NHS and deliberately sought 'alternative' information sources and treatment options.</p> <p>Men were selective in identifying particular therapies to use and sceptical about others, basing their choices on forms of 'evidence' that were personally meaningful: personal stories of individuals who had been helped by CAM; the long history and enduring popularity of some therapies; the plausibility of the mechanism of action; a belief or trust in individual therapies or their providers; scientific evidence. Scientific evidence ranked low in the men's personal decision-making about CAM, while it was recognised as important for NHS support for CAM.</p> <p>Conclusion</p> <p>These male cancer patients valued the support and guidance of 'trusted individuals' in making choices about CAM. Trusted health professionals could also play a significant role in helping patients to make informed choices. Any such dialogue must, however, acknowledge the different standards of evidence used by patients and clinicians to evaluate the benefits or otherwise of CAM therapies. Such open communication could help to foster an environment of mutual trust where patients are encouraged to discuss their interest in CAM, rather than perpetuate covert, undisclosed use of CAM with its attendant potential hazards.</p
Continuous home cage monitoring of activity and sleep in mice during repeated paroxetine treatment and discontinuation
Rationale: Non-invasive home cage monitoring is emerging as a valuable tool to assess the effects of experimental interventions on mouse behaviour. A field in which these techniques may prove useful is the study of repeated selective serotonin reuptake inhibitor (SSRI) treatment and discontinuation. SSRI discontinuation syndrome is an under-researched condition that includes the emergence of sleep disturbances following treatment cessation.
Objectives: We used passive infrared (PIR) monitoring to investigate changes in activity, sleep, and circadian rhythms during repeated treatment with the SSRI paroxetine and its discontinuation in mice.
Methods: Male mice received paroxetine (10 mg/kg/day, s.c.) for 12 days, then were swapped to saline injections for a 13 day discontinuation period and compared to mice that received saline injections throughout. Mice were continuously tracked using the Continuous Open Mouse Phenotyping of Activity and Sleep Status (COMPASS) system.
Results Repeated paroxetine treatment reduced activity and increased behaviourally-defined sleep in the dark phase. These effects recovered to saline-control levels within 24 h of paroxetine cessation, yet there was also evidence of a lengthening of sleep bouts in the dark phase for up to a week following discontinuation.
Conclusions: This study provides the first example of how continuous non-invasive home cage monitoring can be used to detect objective behavioural changes in activity and sleep during and after drug treatment in mice. These data suggest that effects of paroxetine administration reversed soon after its discontinuation but identified an emergent change in sleep bout duration, which could be used as a biomarker in future preclinical studies to prevent or minimise SSRI discontinuation symptoms
Revealing the dynamic relationship between neural population activities in corticoraphe system
Degeneracy and stability in neural circuits of dopamine and serotonin neuromodulators: A theoretical consideration
Degenerate neural circuits perform the same function despite being structurally different. However, it is unclear whether neural circuits with interacting neuromodulator sources can themselves degenerate while maintaining the same neuromodulatory function. Here, we address this by computationally modeling the neural circuits of neuromodulators serotonin and dopamine, local glutamatergic and GABAergic interneurons, and their possible interactions, under reward/punishment-based conditioning tasks. The neural modeling is constrained by relevant experimental studies of the VTA or DRN system using, e.g., electrophysiology, optogenetics, and voltammetry. We first show that a single parsimonious, sparsely connected neural circuit model can recapitulate several separate experimental findings that indicated diverse, heterogeneous, distributed, and mixed DRNVTA neuronal signaling in reward and punishment tasks. The inability of this model to recapitulate all observed neuronal signaling suggests potentially multiple circuits acting in parallel. Then using computational simulations and dynamical systems analysis, we demonstrate that several different stable circuit architectures can produce the same observed network activity profile, hence demonstrating degeneracy. Due to the extensive D2-mediated connections in the investigated circuits, we simulate the D2 receptor agonist by increasing the connection strengths emanating from the VTA DA neurons. We found that the simulated D2 agonist can distinguish among sub-groups of the degenerate neural circuits based on substantial deviations in specific neural populations’ activities in reward and punishment conditions. This forms a testable model prediction using pharmacological means. Overall, this theoretical work suggests the plausibility of degeneracy within neuromodulator circuitry and has important implications for the stable and robust maintenance of neuromodulatory functions
Opportunities for multiscale computational modelling of serotonergic drug effects in Alzheimer’s disease
Alzheimer's disease (AD) is an age-specific neurodegenerative disease that
compromises cognitive functioning and impacts the quality of life of an
individual. Pathologically, AD is characterised by abnormal accumulation of
beta-amyloid (A) and hyperphosphorylated tau protein. Despite research
advances over the last few decades, there is currently still no cure for AD.
Although, medications are available to control some behavioural symptoms and
slow the disease's progression, most prescribed medications are based on
cholinesterase inhibitors. Over the last decade, there has been increased
attention towards novel drugs, targeting alternative neurotransmitter pathways,
particularly those targeting serotonergic (5-HT) system. In this review, we
focused on 5-HT receptor (5-HTR) mediated signalling and drugs that target
these receptors. These pathways regulate key proteins and kinases such as GSK-3
that are associated with abnormal levels of A and tau in AD. We then
review computational studies related to 5-HT signalling pathways with the
potential for providing deeper understanding of AD pathologies. In particular,
we suggest that multiscale and multilevel modelling approaches could
potentially provide new insights into AD mechanisms, and towards discovering
novel 5-HTR based therapeutic targets.Comment: Accepted manuscript in Neuropharmacolog
Large-scale network modelling of interactions between prefrontal cortex and dorsal raphe nucleus using SpiNNaker
Psilocin acutely alters sleep-wake architecture and cortical brain activity in laboratory mice
Serotonergic psychedelic drugs, such as psilocin (4-hydroxy-N,N-dimethyltryptamine), profoundly alter the quality of consciousness through mechanisms which are incompletely understood. Growing evidence suggests that a single psychedelic experience can positively impact long-term psychological well-being, with relevance for the treatment of psychiatric disorders, including depression. A prominent factor associated with psychiatric disorders is disturbed sleep, and the sleep-wake cycle is implicated in the homeostatic regulation of neuronal activity and synaptic plasticity. However, it remains largely unknown to what extent psychedelic agents directly affect sleep, in terms of both acute arousal and homeostatic sleep regulation. Here, chronic electrophysiological recordings were obtained in mice to track sleep-wake architecture and cortical activity after psilocin injection. Administration of psilocin led to delayed REM sleep onset and reduced NREM sleep maintenance for up to approximately 3 h after dosing, and the acute EEG response was associated primarily with an enhanced oscillation around 4 Hz. No long-term changes in sleep-wake quantity were found. When combined with sleep deprivation, psilocin did not alter the dynamics of homeostatic sleep rebound during the subsequent recovery period, as reflected in both sleep amount and EEG slow-wave activity. However, psilocin decreased the recovery rate of sleep slow-wave activity following sleep deprivation in the local field potentials of electrodes targeting the medial prefrontal and surrounding cortex. It is concluded that psilocin affects both global vigilance state control and local sleep homeostasis, an effect which may be relevant for its antidepressant efficacy
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