Neil P. Morris

Perineuronal nets ensheath fast spiking, parvalbumin‐immunoreactive neurons in the medial septum/diagonal band complex

Perineuronal nets, composed of extracellular matrix material, have previously been associated with parvalbumin‐immunoreactive neurons in the medial septum/diagonal band (MS/DB) complex of the rat. The aim of this study was to correlate the presence of perineuronal nets with electrophysiological properties and parvalbumin immunoreactivity in MS/DB neurons. Intracellular recordings were made from cells in a brain slice preparation maintained in vitro, and neurons were characterized into four populations: (i) slow‐firing neurons, (ii) burst‐firing neurons, (iii) fast spiking neurons with narrow action potentials and a small degree of spike frequency adaptation, and (iv) regular spiking neurons with broader action potentials and a high degree of spike frequency adaptation. Following electrophysiological characterization, neurons were filled with biocytin, processed for parvalbumin immunoreactivity and stained for perineuronal nets using Wisteria floribunda lectin. The three substances were viewed with triple fluorescence. Fast spiking, nonadapting neurons, shown previously to contain parvalbumin immunoreactivity, were nearly all ensheathed by perineuronal nets. There was a population of small parvalbumin‐immunoreactive neurons which did not possess perineuronal nets, and which were not encountered with the intracellular electrodes. The other three neuron types in the MS/DB did not contain parvalbumin immunoreactivity or perineuronal nets. In keeping with this neurochemical profile for electrophysiologically identified neurons, burst‐firing neurons had action potential parameters more similar to those of regular spiking than of fast spiking neurons. We conclude that fast spiking neurons, presumed to be GABAergic septohippocampal projection neurons, are surrounded by supportive structures to enable the high level of neuronal discharge required for producing disinhibition of hippocampal pyramidal neurons.

Morphology of local axon collaterals of electrophysiologically characterised neurons in the rat medial septal/ diagonal band complex.

Neurons in the medial septal/diagonal band complex (MS/DB) in vivo exhibit rhythmic burst‐firing activity that is phase‐locked with the hippocampal theta rhythm. The aim was to assess the morphology of local axon collaterals of electrophysiologically identified MS/DB neurons using intracellular recording and biocytin injection in vitro. Cells were classified according to previous criteria into slow‐firing, fast‐spiking, regular‐spiking, and burst‐firing neurons; previous work has suggested that the slow‐firing neurons are cholinergic and that the other types are GABAergic. A novel finding was the existence of two types of burst‐firing neuron. Type I burst‐firing neurons had significantly longer duration after hyperpolarisation potentials when held at −60 mV, and at −75 mV, type I neurons exhibited a low‐threshold spike with more rapid activation and inactivation kinetics than those of type II neurons. We have, also for the first time, described the main features of the local axon collaterals of the five neuron types. All filled neurons possessed a main axon that gave forth 1–12 local primary axon collaterals. All electrophysiological types, except for the type I burst‐firing neuron, had a main axon that coursed toward the fornix. Myelination of the main axon was a prominent feature of all but the slow‐firing neurons. Branching of the primary axon collaterals of the fast‐spiking and type I burst‐firing neurons was more extensive than that of the other cell types, with those of the slow‐firing neurons exhibiting the least branching. All cell types possessed axon collaterals of the en passant type, and some in addition had twiglike or basketlike axon terminals. All cell types made synapses on distal dendrites; a proportion of the fast‐spiking and burst‐firing cells in addition had basketlike terminals that made synaptic contacts on proximal dendrites and on somata. Two morphological types of somata were postsynaptic to the basket cells: large (20–30‐μm) oval cells with dark cytoplasm, and large oval cells with paler cytoplasm, often with an apical dendrite. The presence of lamellar bodies in the large dark neurons suggests that they may be cholinergic neurons, because previous work has localised these structures in some neurons that stain for choline acetyltransferase. Our work suggests therefore that there may be GABAergic neurons in the MS/DB that form basket synaptic contacts on at least two types of target cell, possibly cholinergic and GABAergic neurons, which means that the basket cells could play a key role in the generation of rhythmic activity in the MS/DB. J. Comp. Neurol. 430:410–432, 2001.

Kv3 voltage-gated potassium channels regulate neurotransmitter release from mouse motor nerve terminals.

Voltage‐gated potassium (Kv) channels are critical to regulation of neurotransmitter release throughout the nervous system but the roles and identity of the subtypes involved remain unclear. Here we show that Kv3 channels regulate transmitter release at the mouse neuromuscular junction (NMJ). Light‐ and electron‐microscopic immunohistochemistry revealed Kv3.3 and Kv3.4 subunits within all motor nerve terminals of muscles examined [transversus abdominus, lumbrical and flexor digitorum brevis (FDB)]. To determine the roles of these Kv3 subunits, intracellular recordings were made of end‐plate potentials (EPPs) in FDB muscle fibres evoked by electrical stimulation of tibial nerve. Tetraethylammonium (TEA) applied at low concentrations (0.05–0.5 mm), which blocks only a few known potassium channels including Kv3 channels, did not affect muscle fibre resting potential but significantly increased the amplitude of all EPPs tested. Significantly, this effect of TEA was still observed in the presence of the large‐conductance calcium‐activated potassium channel blockers iberiotoxin (25–150 nm) and Penitrem A (100 nm), suggesting a selective action on Kv3 subunits. Consistent with this, 15‐µm 4‐aminopyridine, which blocks Kv3 but not large‐conductance calcium‐activated potassium channels, enhanced evoked EPP amplitude. Unexpectedly, blood‐depressing substance‐I, a toxin selective for Kv3.4 subunits, had no effect at 0.05–1 µm. The combined presynaptic localization of Kv3 subunits and pharmacological enhancement of EPP amplitude indicate that Kv3 channels regulate neurotransmitter release from presynaptic terminals at the NMJ.

Characterisation of hyperpolarization-activated currents (Ih) in the medial septum/diagonal band complex in the mouse

Hyperpolarization-activated cyclic nucleotide gated (HCN) channel subunits are distributed widely, but selectively, in the central nervous system, and underlie hyperpolarization-activated currents (I(h)) that contribute to rhythmicity in a variety of neurons. This study investigates, using current and voltage-clamp techniques in brain slices from young mice, the properties of I(h) currents in medial septum/diagonal band (MS/DB) neurons. Subsets of neurons in this complex, including GABAergic and cholinergic neurons, innervate the hippocampal formation, and play a role in modulating hippocampal theta rhythm. In support of a potential role for I(h) in regulating MS/DB firing properties and consequently hippocampal neuron rhythmicity, I(h) currents were present in around 60% of midline MS/DB complex neurons. The I(h) currents were sensitive to the selective blocker ZD7288 (10 microM). The I(h) current had a time constant of activation of around 220 ms (at -130 mV), and tail current analysis revealed a half-activation voltage of -98 mV. Notably, the amplitude and kinetics of I(h) currents in MS/DB neurons were insensitive to the cAMP membrane permeable analogue 8-bromo-cAMP (1 mM), and application of muscarine (100 microM). Immunofluoresence using antibodies against HCN1, 2 and 4 channel subunits revealed that all three HCN subunits are expressed in neurons in the MS/DB, including neurons that express the calcium binding protein parvalbumin (marker of fast spiking GABAergic septo-hippocampal projection neurons). The results demonstrate, for the first time, that specific HCN channel subunits are likely to be coexpressed in subsets of MS/DB neurons, and that the resultant I(h) currents show both similarities, and differences, to previously described I(h) currents in other CNS neurons.

Localization and function of the Kv3.1b subunit in the rat medulla oblongata: focus on the nucleus tractus solitarii.

The voltage‐gated potassium channel subunit Kv3.1 confers fast firing characteristics to neurones. Kv3.1b subunit immunoreactivity (Kv3.1b‐IR) was widespread throughout the medulla oblongata, with labelled neurones in the gracile, cuneate and spinal trigeminal nuclei. In the nucleus of the solitary tract (NTS), Kv3.1b‐IR neurones were predominantly located close to the tractus solitarius (TS) and could be GABAergic or glutamatergic. Ultrastructurally, Kv3.1b‐IR was detected in NTS terminals, some of which were vagal afferents. Whole‐cell current‐clamp recordings from neurones near the TS revealed electrophysiological characteristics consistent with the presence of Kv3.1b subunits: short duration action potentials (4.2 ± 1.4 ms) and high firing frequencies (68.9 ± 5.3 Hz), both sensitive to application of TEA (0.5 mm) and 4‐aminopyridine (4‐AP; 30 μm). Intracellular dialysis of an anti‐Kv3.1b antibody mimicked and occluded the effects of TEA and 4‐AP in NTS and dorsal column nuclei neurones, but not in dorsal vagal nucleus or cerebellar Purkinje cells (which express other Kv3 subunits, but not Kv3.1b). Voltage‐clamp recordings from outside‐out patches from NTS neurones revealed an outward K+ current with the basic characteristics of that carried by Kv3 channels. In NTS neurones, electrical stimulation of the TS evoked EPSPs and IPSPs, and TEA and 4‐AP increased the average amplitude and decreased the paired pulse ratio, consistent with a presynaptic site of action. Synaptic inputs evoked by stimulation of a region lacking Kv3.1b‐IR neurones were not affected, correlating the presence of Kv3.1b in the TS with the pharmacological effects.

Podcasts and Mobile Assessment Enhance Student Learning Experience and Academic Performance

Abstract The aim of this study was to combine podcasts of lectures with mobile assessments (completed via SMS on mobile telephones) to assess the effect on examination performance. Students (n = 100) on a final year, research-led, module were randomly divided into equal sized control and trial groups. The trial group were given access to podcasts / mobile formative assessments for lectures on the module. Towards the end of the module, all students on the module completed a ‘mock’ examination on the material in the lectures. Students in the trial group who listened to podcasts of the lectures and completed mobile assessments (n = 31) performed significantly better in the formative assessment (58.1±1, mean ± S.E.M; P<0.05, Student’s t-test) than other students on the module (52.2 ± 2; n = 54). Students accessed the podcasts via iTunes (or similar software; 38%), from the institutional virtual learning environment (31%), or using a combination of the two (31%). Interestingly, only around 21% of students listened to the majority of their podcasts away from a computer. The results of this study indicate that providing supporting resources does have a positive impact on student performance.

Galanin‐immunoreactive synaptic terminals on basal forebrain cholinergic neurons in the rat

Previous studies have indicated that galanin is one of the most abundant peptides in the basal forebrain and that it has a significant modulatory influence on cholinergic transmission. The aim of the present study was to use a light electron microscopic correlation technique to determine whether galanin‐immunoreactive terminals form synaptic contacts with basal forebrain cholinergic cells of the rat. Sections from fixed‐perfused brains were stained at the light and electron microscopic levels for galanin and choline acetyltransferase immunoreactivity in the same section by using a dual‐colour immunohistochemical method. The results showed that galanin‐immunoreactive axonal terminals are unevenly distributed in the medial septal nucleus, the diagonal band, and the nucleus basalis. Galanin‐positive synapses were most prominent on choline acetyltransferase‐positive neurons in the lateral parts of the nucleus of the diagonal band and in the posterior half of the nucleus basalis, which is where there was the greatest overlap between the distribution of galanin‐immunoreactive terminals and choline acetyltransferase‐positive neurons. The origins of these galanin‐positive terminals are not known, but the results confirm that the basal forebrain galaninergic system has a synaptic influence on basal forebrain cholinergic neurons in the rat. J. Comp. Neurol. 383:82–93, 1997.

Moving Through MOOCS: Pedagogy, Learning Design and Patterns of Engagement

Massive open online courses (MOOCs) are part of the lifelong learning experience of people worldwide. Many of these learners participate fully. However, the high levels of dropout on most of these courses are a cause for concern. Previous studies have suggested that there are patterns of engagement within MOOCs that vary according to the pedagogy employed. The current paper builds on this work and examines MOOCs from different providers that have been offered on the FutureLearn platform. A cluster analysis of these MOOCs shows that engagement patterns are related to pedagogy and course duration. Learners did not work through a three-week MOOC in the same ways that learners work through the first three weeks of an eight-week MOOC.

Multimedia Interactive eBooks in Laboratory Bioscience Education.

Abstract Bioscience students in the UK higher education system are making increasing use of technology to support their learning within taught classes and during private study. This experimental study was designed to assess the role for multimedia interactive eBooks in bioscience laboratory classes, delivered using a blended learning approach. Thirty-nine second-year students on a Biomedical Science undergraduate course in a UK university were grouped using an experimental design into alternating trial and control groups and provided with pre-configured iPad tablet devices containing multimedia interactive eBooks. Data collection involved weekly surveys including quantitative and qualitative responses, and analysis of summative assessment marks. Analysis of the results using descriptive statistics methods showed that students made extensive use of eBooks in practical classes and over 70% of students agreed that the eBooks were beneficial for learning. However, less than 40% of students indicated a preference for eBooks over traditional paper protocols for practical-based classes. Although the eBooks were well used by students, they had no statistically significant effect on assessment marks. Overall, the study highlighted the positive feedback from students relating to multimedia interactive eBooks for supporting students’ learning, but illustrated that there are other factors affecting adoption of new technologies.

Teaching as a Design Science: Building Pedagogical Patterns for Learning and Technology. By Diana Laurillard

Muslims in Britain. This has an adverse affect since the portrayal of Islam is much more profound in contemporary society because of the place of Islam in the narratives outside school. Hence, ‘the textbooks on Islam present a view of Muslim beliefs and communities that appears to be positive – but in a context that is divorced from the world in which pupils encounter Islam through other channels’ (p. 64). Another excellent chapter is the fourth one, entitled ‘Islam, Education and the Home Office’, where Revell highlights the political context of teaching world religions, especially Islam, in schools. She states ‘The Home Office sees the teaching of Islam and other world religions as a key part of their strategy to oppose terrorism’ (p. 65). Through this chapter the author discusses the initiatives promoted by the Home Office, such as Prevent, Contest and Resilience, successfully contextualising the teaching of Islam in schools. Her final chapter, ‘Tolerance and Representation’, concludes the book by arguing that ‘a new representation of Islam, drawn not by government or by the media but by those who are represented, should be evolved and adapted in education and wider society’ (p. 117). This in my opinion was a very interesting and fruitful read that informs the reader about how Islam is represented in education in Britain and how this representation is related with various political, social and ideological agendas. This is a book that raises many pertinent and challenging questions, but in a very enjoyable and accessible way. This book in general is superb and essential for all readers interested in the topic of RE and Islam in schools.