Kathleen Neal

Strain‐specific genetics, anatomy and function of enteric neural serotonergic pathways in inbred mice

Serotonin (5‐HT) powerfully affects small intestinal motility and 5‐HT‐immunoreactive (IR) neurones are highly conserved between species. 5‐HT synthesis in central neurones and gastrointestinal mucosa depends on tissue‐specific isoforms of the enzyme tryptophan hydroxylase (TPH). RT‐PCR identified strain‐specific expression of a polymorphism (1473C/G) of the tph2 gene in longitudinal muscle–myenteric plexus preparations of C57Bl/6 and Balb/c mice. The former expressed the high‐activity C allele, the latter the low‐activity G allele. Confocal microscopy was used to examine close contacts between 5‐HT‐IR varicosities and myenteric neurones immunoreactive for neuronal nitric oxide synthase (NOS) or calretinin in these two strains. Significantly more close contacts were identified to NOS‐ (P < 0.05) and calretinin‐IR (P < 0.01) neurones in C57Bl/6 jejunum (NOS 1.6 ± 0.3, n= 52; calretinin 5.2 ± 0.4, n= 54), than Balb/c jejunum (NOS 0.9 ± 0.2, n= 78; calretinin 3.5 ± 0.3, n= 98). Propagating contractile complexes (PCCs) were identified in the isolated jejunum by constructing spatiotemporal maps from video recordings of cannulated segments in vitro. These clusters of contractions usually arose towards the anal end and propagated orally. Regular PCCs were initiated at intraluminal pressures of 6 cmH2O, and abolished by tetrodotoxin (1 μm). Jejunal PCCs from C57Bl/6 mice were suppressed by a combination of granisetron (1 μm, 5‐HT3 antagonist) and SB207266 (10 nm, 5‐HT4 antagonist), but PCCs from Balb/c mice were unaffected. There were, however, no strain‐specific differences in sensitivity of longitudinal muscle contractions to exogenous 5‐HT or blockade of 5‐HT3 and 5‐HT4 receptors. These data associate a genetic difference with significant structural and functional consequences for enteric neural serotonergic pathways in the jejunum.

Mapping 5-HT inputs to enteric neurons of the guinea-pig small intestine

5-HT released by gastrointestinal mucosa and enteric interneurons has powerful effects on gut behavior. However, the targets of 5-HT-containing neurons within enteric circuits are not well characterized. We used antisera against 5-HT and selected markers of known enteric neuron types to investigate the connections made by 5-HT-containing neurons in the guinea-pig jejunum. Confocal microscopy was used to quantify the number of 5-HT-immunoreactive varicosities apposed to immunohistochemically identified cell bodies. Large numbers of varicosities were identified apposing cholinergic secretomotor neurons, immunoreactive for neuropeptide Y, in both myenteric and submucous plexuses. Subgroups of neurons identified by calretinin (ascending interneurons) and nitric oxide synthase (descending interneurons and inhibitory motor neurons) immunoreactivity were also apposed by many varicosities. Longitudinal muscle motor neurons (calretinin immunoreactive) and AH/Dogiel type II (sensory) neurons (calbindin immunoreactive) were apposed by small numbers of varicosities. Combined retrograde tracing and immunohistochemistry were used to identify excitatory circular muscle motor neurons; these were encircled by 5-HT-immunoreactive varicosities, but the appositions could not be quantified. We suggest that 5-HT-containing interneurons are involved in secretomotor pathways and pathways to subgroups of other interneurons, but not longitudinal muscle motor neurons. There also appear to be connections between 5-HT-containing interneurons and excitatory circular muscle motor neurons. Physiological evidence demonstrates a functional connection between 5-HT-containing interneurons and AH/Dogiel type II neurons, but few 5-HT-immunoreactive varicosities were observed apposing calbindin-immunoreactive cell bodies. Taken together these results suggest that neural 5-HT may have significant roles in excitatory pathways regulating both motility and secretion.

Targets of myenteric interneurons in the guinea-pig small intestine

Abstract  Polarized outputs of myenteric interneurons in guinea‐pig small intestine have been well studied. However, the variety of motility patterns exhibited suggests that some interneuron targets remain unknown. We used antisera selected to distinguish interneuron varicosities and known myenteric neuron types to investigate outputs of three interneuron classes in guinea‐pig jejunum; two classes of descending interneurons immunoreactive (IR) for somatostatin (SOM) or nitric oxide synthase (NOS)/vasoactive intestinal peptide (VIP), and one class of ascending interneurons [calretinin/enkephalin (ENK)‐IR]. Varicosities apposed to immunohistochemically identified cell bodies were quantified by confocal microscopy. Intrinsic sensory neurons (calbindin‐IR) were apposed by few varicosities. Cholinergic secretomotor neurons (neuropeptide Y‐IR) were apposed by many SOM‐IR varicosities. Longitudinal muscle excitatory motor neurons (calretinin‐IR) were apposed by some VIP‐ and ENK‐IR varicosities, but few SOM‐IR varicosities. Ascending interneurons (calretinin‐IR) were apposed by many varicosities of all types. NOS‐IR interneurons and inhibitory motor neurons were apposed by numerous VIP‐IR and SOM‐IR varicosities. NOS‐IR short inhibitory motor neurons were apposed by significantly fewer ENK‐IR varicosities than other NOS‐IR neurons. Based on the specific chemical coding of ascending (ENK) and descending (SOM) interneurons, we conclude that cholinergic secretomotor neurons and short inhibitory neurons are located in descending reflex pathways, while ascending interneurons and NOS‐IR descending interneurons are focal points at which ascending and descending pathways converge.

From Letters to Loyalty: Aline la Despenser and the Meaning(s) of a Noblewoman’s Correspondence in Thirteenth-Century England

Sometime between the summer of 1273, and early August 1274, the Countess of Norfolk, Aline la Despenser, sent a letter to the Chancellor of England.1 This was, in many ways, a completely unremarkable letter concerning a rather banal administrative matter; hardly the place one might naturally look for evidence of intersections between gender, emotion, and authority. Yet, as I argue in this chapter, Aline’s letter was in fact a finely tuned articulation of affective persuasion. The beauty of its design lay in a delicate weaving between observing the expectations shaping letters of governance, and transgressing them in targeted and gendered ways which become clear when the letter is read against its particular context. Through simultaneous reproduction and disordering of the rules of letter-writing, it sought to evoke a range of positive responses in one person — the chancellor to whom it was addressed — in ways uniquely reflective of the relationship between him and its sender, the countess. Close reading of Aline’s letter thus reveals how all senders of letters to royal officers might manipulate affective rhetoric to achieve their political, legal, or fiscal aims: it is a case study of how emotion and authority regularly interacted in medieval England. Further, it illuminates the circumstances in which women could enter epistolary exchange of this kind, and the gendered rhetorical strategies they might use when the opportunity to do so arose.

Words as Weapons in the Correspondence of Edward I with Llywelyn ap Gruffydd

The correspondence exchanged by Edward I of England and Llywelyn ap Gruffydd, Prince of Wales, in the late thirteenth century has traditionally been read for its legal and jurisdictional implications. However, as Rees Davies noted, language was itself a weapon in medieval Anglo-Welsh conflict. From this assumption, I examine a single letter exchange to investigate the construction and function of royal epistolary language. I suggest that traditional and formulaic elements were adapted to strategic expression of the authority and longevity of royal power, and that silences were equally intentional and rhetorically forceful weapons in the campaign to dominate Wales.

The Journey of a Book: Bartholomew the Englishman and the Properties of Things (review)

In this insightful work, Elizabeth Keen traces the text of a medieval compendium, De proprietatibus rerum, on its journey from thirteenth-century Europe to the library of Sir Joseph Banks. Carefully following each separating or converging strand of meaning or way of reading, like so many lines on a complicated map, she illustrates how and why this particular text remained a living work among English readers over so many centuries, and casts light on the mental universes of its diverse readerships. Such themes as enclosure and mendicancy, orthodoxy and heterodoxy, preaching and contemplation, agricultural practice, land ownership, book ownership, memory, allegory, social order and disruption, nationalism, and Protestantism are all part of this rich topography. There is a pleasing symmetry in the fact that this study of a book about everything, itself becomes a book about everything, as the author’s focus widens to accommodate each new context. Despite the complexity of her task, Keen accomplishes it with clarity and a steady momentum of argument. The Journey of a Book is thus a satisfying, as well as informative and thought-provoking, read. Irrespective of the contested identity of Bartholomew himself, Keen’s point of departure is that his work, ‘Properties’, is a compilatio of the late twelfth/early thirteenth century, and is located within a firmly Franciscan milieu. She emphasises, beginning with an interesting historiographical discussion, how such works were both authoritative collections of important facts and opinions, and exegetical texts intended to illustrate the workings of God’s creation and the path to salvation. Although medieval compilatio exist in a continuum with scientific observation writings of later periods, the medieval works were not merely early, or flawed, examples of the scientific endeavour, but a distinct genre with their own intrinsic worth. However, Keen also highlights that the meaning of ‘Properties’ was not static, but in constant flux over the long duration of its reception by English audiences. This is perhaps a truism, but one which has never been as convincingly or empathetically teased apart as in this book.

Transforming the Medieval World: Uses of Pragmatic Literacy in the Middle Ages (review)

Transforming the Medieval World has an unusual format – CD-ROM and accompanying book – deliberately selected to illustrate a central theoretical thesis. Namely, that ‘the concept of an “authorised original”, which was to be preserved as far as possible in its unchanged state, was largely foreign to medieval written culture’ (p. 5). It is clear from the introduction that the editors consider this thesis and their chosen electronic medium to be inextricably related. They argue that the fixed nature of the written word intrinsically obstructs the full explication of ‘mouvance’, the ‘fluid and open nature’ (p. 3) of medieval manuscript culture, while multimedia platforms are freed from the necessity of ‘a system of comments and notes to present variations’ (p. 7). Indeed, given this position, it is unclear why a print version was produced at all. The editors are very excited by the possibilities of the new medium, spending 16 pages of introduction (in the print version) justifying their choice and extolling its virtues. In some ways they are vindicated; the CD-ROM is a handsome vehicle, but it is not without flaws, most of which arise from the decisions of the editors rather than the medium itself. The core work comprises eleven multimedia presentations; nine cover various document genres from account books to world chronicles, while the remaining two focus on ‘Book Communities’ and illumination respectively. The digital presentation is impressive and has evidently been carefully considered to emphasise key points and encourage readers to form new associations, whilst discouraging interrupted attention to essential ideas. This is at least partially successful. The presentations are richly illustrated and make effective use of moving images to show texts being taken apart and reassembled, adapted, and rewritten. Menus are cleverly designed so that readers can choose whether to pursue the information by document genre, geographical region, period or thematic subheading. There are engaging spoken introductions to each section, and some useful interactive features such as clickable transcriptions and translations, and zoom function on most images. The option for printable text versions will be appreciated by anyone wanting to use the materials in class.

Orality and Literacy in the Middle Ages: Essays on a Conjunction and its Consequences in Honour of D. H. Green (review)

This volume of essays, covering a broad geographical and temporal sweep of medieval Europe, explores the symbiosis of orality and literacy, and is conceived as a tribute to one of the chief exponents of this idea, Dennis Green. Hence, the various contributors focus on the constant interrelationship between spoken and written, aural and visual, immediate and distanced modes of communication, rather than telling a tale of the progressive victory of writing over speech. This is not a new approach, but in the main the essays presented here make a genuine contribution to the field, drawing out useful general observations from their respective case studies. A key theme concerns unravelling evidence for the audiences and ways of reading envisaged by writers. Audiences could include private readers, ‘corporate’ readers engaged in listening and discussing, and the performative readers required to present written works to listeners. Any or all of these were assumed by writers according to period and context. Individual reading is explored by Sylvia Hout and Jürgen Wolf. Wolf employs the evidence of vernacular instructions, preambles and marginal notes in Latin psalters to demonstrate that lay people as well as clerics understood and expected to use religious texts actively. Adopting a different approach, Hout examines pictorial evidence from religious books to show how individuals were encouraged to use the text before them as an imaginative and meditative springboard for contemplation. The written word was enhanced by visual references which coaxed a multitude of related stories, images and metaphors to the mind’s eye. Scenes of corporate reading, in which learned or noble men gather to hear and discuss texts are central, in different ways, to the articles by Katherine O’Brien O’Keefe and Joyce Coleman. O’Brien O’Keefe shows how King Alfred and his circle considered corporate reading essential to proper understanding. Coleman identifies scenes of corporate reading in the illuminated frontispieces of Cité de Dieu manuscripts emanating from the court of Philip the Good. In her analysis, the image of a scholarly, clerical crowd discussing Augustine’s Civitas Dei illustrates both the imagined audience of the work and the superiority of clerical over secular knowledge, by representing the generations of scholars who had contributed to understanding the text at hand. Coleman also emphasises that images could have