A quantification of the relationship between neuronal responses in the rat rostral ventromedial medulla and noxious stimulation-evoked withdrawal reflexes

The rostral ventromedial medulla (RVM) regulates a range of involuntary behaviours but is most often associated with nociception via the action of pronociceptive ON cells and antinociceptive OFF cells. The phasic responses of ON and OFF cells determine whether or not incoming noxious signals provoke a withdrawal reflex, and previous studies have suggested that reflex RVM activity patterns actively shape motor output. Here we challenged the model by using juvenile rats, which are known to exhibit markedly different reflex responses compared with adults. By recording single-cell activity in the RVM and the electromyography responses of hindlimb flexor muscles to noxious thermal stimulation we found that the juvenile reflex had a shorter onset latency, was larger in amplitude and exhibited a decreased rise time compared with the adult reflex. The responses of ON and OFF cells faithfully tracked the shorter onset latency of the reflex by also responding earlier and, thus, still preceded the reflex. However, neither the reflex amplitude nor the ongoing response profile was predicted by the firing rate of RVM cells in either age group. Instead we found a close correspondence between RVM activity and the reflex only during the initiation of the response. Furthermore, the short rise time of the juvenile reflex was reflected in higher rates of change of both ON and OFF cell firing. Our data suggest that the RVM is associated only with the initiation of reflexes and does not shape ongoing muscle activity, which is more likely to be subserved by downstream spinal processes

Manganese-enhanced magnetic resonance imaging depicts brain activity in models of acute and chronic pain: a new window to study experimental spontaneous pain?

Application of functional imaging techniques to animal models is vital to understand pain mechanisms, but is often confounded by the need to limit movement artefacts with anaesthesia, and a focus on evoked responses rather than clinically relevant spontaneous pain and related hyperalgesia. The aim of the present study was to investigate the potential of manganese-enhanced magnetic resonance imaging (MEMRI) to measure neural responses during on-going pain that underpins hyperalgesia in pre-clinical models of nociception. As a proof of concept that MEMRI is sensitive to the neural activity of spontaneous, intermittent behaviour, we studied a separate positive control group undergoing a voluntary running wheel experiment. In the pain models, pain behaviour (weight bearing asymmetry and hindpaw withdrawal thresholds (PWTs)) was measured at baseline and following either intra-articular injection of nerve growth factor (NGF, 10 µg/50 µl; acute pain model, n=4 rats per group), or the chondrocyte toxin monosodium iodoacetate (MIA, 1 mg/50 µl; chronic model, n=8 rats per group), or control injection. Separate groups of rats underwent a voluntary wheel running protocol (n=8 rats per group). Rats were administered with paramagnetic ion Mn2+ as soluble MnCl2 over seven days (subcutaneous osmotic pump) to allow cumulative activity-dependent neural accumulation in the models of pain, or over a period of running. T1-weighted MR imaging at 7 T was performed under isoflurane anaesthesia using a receive-only rat head coil in combination with a 72 mm volume coil for excitation. The pain models resulted in weight bearing asymmetry (NGF: 20.0 ± 5.2%, MIA: 15 ± 3%), and a reduction in PWT in the MIA model (8.3 ± 1.5 g) on the final day of assessment before undergoing MR imaging. Voxel-wise and region-based analysis of MEMRI data did not identify group differences in T1 signal. However, MnCl2 accumulation in the VTA, right Ce amygdala, and left cingulate was negatively correlated with pain responses (greater differences in weight bearing), similarly MnCl2 accumulation was reduced in the VTA in line with hyperalgesia (lower PWTs), which suggests reduced regional activation as a result of the intensity and duration of pain experienced during the 7 days of MnCl2 exposure. Motor cortex T1-weighted signal increase was associated with the distance ran in the wheel running study, while no between group difference was seen. Our data suggest that on-going pain related signal changes identified using MEMRI offers a new window to study the neural underpinnings of spontaneous pain in rats

Lamina-specific population encoding of cutaneous signals in the spinal dorsal horn using multi-electrode arrays

The dorsal spinal cord (DH) is a complex laminar structure integrating peripheral signals into the central nervous system. Spinal somatosensory processing is commonly measured electrophysiologically in vivo by recording the activity of individual Wide Dynamic Range neurons in the deep DH and extrapolating their behaviour to all cells in every lamina. This fails to account for the specialised processes that occur in each lamina and the considerable heterogeneity in cellular phenotype within and between laminae. Here we overcome this oversimplification by employing linear multi‐electrode arrays (MEAs) in the DH of anaesthetized rats to simultaneously measure activity across all laminae. The MEAs, comprised of 16‐channels, were inserted into the lumbar dorsal horn and peripheral neurones activated electrically via transcutaneous electrodes and ethologically with von Frey hairs (vFh) or an aluminium heating block. Ascending electrical stimuli showed fibre thresholds with distinct dorso‐ventral innervation profiles. Wind up was observed across the DH during the C‐fibre and post‐discharge latencies following 0.5Hz stimulation. Intrathecal application of morphine (5ng/50ul) significantly reduced Aδ and C‐fibre evoked activity in deep and superficial DH. Light vFhs (≤10g) predominantly activated intermediate and deep laminae whereas noxious vFh (26g) also activated the superficial laminae. Noxious heat (55°C) induced significantly greater activity in the superficial and deep laminae than the innocuous control (30°C). The application of these arrays produced the first description of the processing of innocuous and noxious stimuli throughout the intact DH

Risk-based learning games improve long-term retention of information among school pupils

Risk heightens motivation and, if used appropriately, may have the potential to improve engagement in the classroom. We have developed a risk-based learning game for school pupils in order to test whether such learning games can improve later recall of information. The study was performed during a series of public engagement workshops delivered by undergraduate students. Undergraduate neuroscience students delivered 90-minute science workshops to 9–10 year old school pupils (n = 448) that were divided into ‘Risk’, ‘No risk’ and ‘Control’ classes. ‘Risk’ classes received periodic multiple-choice questions (MCQs) during the workshops which required small teams of pupils to assign tokens to the answer(s) they believed to be correct. Tokens assigned to the correct answer were returned to the group and an equal number given back as a prize; tokens assigned to incorrect answers were lost. Participation was incentivised by the promise of a brain-related prize to the team with the most tokens at the end of the workshop. ‘No risk’ classes received MCQs without the risk component whilst the ‘Control’ classes received no MCQs. When presented with a neuroscience quiz based on workshop content at the end of the workshop, pupils in the ‘Risk’ classes exhibited significantly greater recall of information one week later. Quiz scores were higher than scores from the day of the workshop which suggested pupils may have discussed the workshop content outside of the classroom, thereby increasing knowledge over and above what was learned during the workshop. This is supported by feedback from pupils in ‘Risk’ classes which indicated that ‘Risk’ workshops were more interesting than ‘No risk’ and ‘Control’ workshops. These data suggest that there is a role for risk in the classroom but further -investigations are required to elucidate the causal mechanisms of improved retention of information

Overcoming the barriers to greater public engagement

Integrating science communication training into an undergraduate research project encourages greater academic involvement in public engagement, maximizes audience size, and provides high-quality research data

The evolution of insecticide resistance in the peach-potato aphid, Myzus persicae

© 2014 The Authors. Published by Elsevier Ltd. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence e (http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.The peach potato aphid, Myzus persicae is a globally distributed crop pest with a host range of over 400 species including many economically important crop plants. The intensive use of insecticides to control this species over many years has led to populations that are now resistant to several classes of insecticide. Work spanning over 40 years has shown that M. persicae has a remarkable ability to evolve mechanisms that avoid or overcome the toxic effect of insecticides with at least seven independent mechanisms of resistance described in this species to date. The array of novel resistance mechanisms, including several ‘first examples’, that have evolved in this species represents an important case study for the evolution of insecticide resistance and also rapid adaptive change in insects more generally. In this review we summarise the biochemical and molecular mechanisms underlying resistance in M. persicae and the insights study of this topic has provided on how resistance evolves, the selectivity of insecticides, and the link between resistance and host plant adaptation.Peer reviewedFinal Published versio

Neuroscience: viable applications in education?

As a relatively young science, neuroscience is still finding its feet in potential collaborations with other disciplines. One such discipline is education, with the field of neuroeducation being on the horizon since the 1960s. However, although its achievements are now growing, the partnership has not been as successful as first hopes suggested it should be. Here the authors discuss the theoretical barriers and potential solutions to this, which have been suggested previously, with particular focus on levels of research in neuroscience and their applicability to education. Moreover, they propose that these theoretical barriers are driven and maintained by practical barriers surrounding common language and research literacy. They propose that by overcoming these practical barriers through appropriate training and shared experience, neuroeducation can reach its full potential

Effects of urethane anaesthesia on sensory processing in the rat barrel cortex revealed by combined optical imaging and electrophysiology

The spatiotemporal dynamics of neuronal assemblies evoked by sensory stimuli have not yet been fully characterised, especially the extent to which they are modulated by prevailing brain states. In order to examine this issue, we induced different levels of anaesthesia, distinguished by specific electroencephalographic indices, and compared somatosensory-evoked potentials (SEPs) with voltage-sensitive dye imaging (VSDI) responses in the rat barrel cortex evoked by whisker deflection. At deeper levels of anaesthesia, all responses were reduced in amplitude but, surprisingly, only VSDI responses exhibited prolonged activation resulting in a delayed return to baseline. Further analysis of the optical signal demonstrated that the reduction in response amplitude was constant across the area of activation, resulting in a global down-scaling of the population response. The manner in which the optical signal relates to the various neuronal generators that produce the SEP signal is also discussed. These data provide information regarding the impact of anaesthetic agents on the brain, and show the value of combining spatial analyses from neuroimaging approaches with more traditional electrophysiological techniques

Teaching medical students basic neurotransmitter pharmacology using primary research resources

Teaching pharmacology to medical students has long been seen as a challenge, and one to which a number of innovative approaches have been taken. In this article, we describe and evaluate the use of primary research articles in teaching second-year medical students both in terms of the information learned and the use of the papers themselves. We designed a seminar where small groups of students worked on different neurotransmitters before contributing information to a plenary session. Student feedback suggested that when the information was largely novel, students learned considerably more. Crucially, this improvement in knowledge was seen even when they had not directly studied a particular transmitter in their work groups, suggesting a shared learning experience. Moreover, the majority of students reported that using primary research papers was easy and useful, with over half stating that they would use them in future study