The distribution of short-tailed shrews, Blarina carolinensis and B. brevicauda, demonstrates contiguous allopatry in peninsular situations in the Coastal Plain of Virginia, and in other areas. The distribution of these two species is unusual in that they do not exhibit syntopy except within a narrow corridor along the borders of their ranges. Interestingly, along the Coastal Plain of Virginia, B. carolinensis is generally found only at the distal ends of the peninsular areas, existing as local populations that appear to be isolated from each other and from the primary population that exists in south-central Virginia. It is thought that the disjunct distribution of B. carolinensis populations results from the unique physiography of Chesapeake Bay, namely peninsular water barriers, and that the intervening distribution of its congener, B. brevicuada, should promote morphometric and population differentiation due to isolation. Whether populations of B. carolinensis along the Coastal Plain of Virginia are truly isolated (and possibly morphologically and/or genetically dissimilar to the continuous southeastern Unites States distribution) is unknown. I examined cranial morphometrics and molecular genetic characters (mitochondrial DNA control region and exon-primed intron-crossing nuclear DNA, EPIC) from peninsular populations of B. carolinensis and compared them to shrews of the mainland population to address this question. The sources of specimens were shrews ensnared in discarded bottles along roadsides, museum skins, and specimens frozen in alcohol. Principle coordinate analyses did not indicate a correlation between cranial morphology and genetic structuring of the populations. MANOVA analyses correlate distinct geographic regions with variation of four cranial measurements related to length. A 492 base pair region of the mitochondrial control region was obtained for many specimens and found to be polymorphic resulting in 27 unique haplotypes evenly partitioned across populations reflecting low levels of differentiation. Nuclear DNA markers were not found to exhibit repeatable amplification and therefore were not useful. Genetic variance detected among populations ranged from ΦPT = 0.001 to 0.045. The effective number of migrants (Nem), as estimated from the standard relationship with ФPT values, indicated panmixia. Both sets of observations indicated that physiography and B. brevicauda are not as severe factors limiting migration among the Coastal Plain populations of B. carolinensis as was thought.

Les troubles dépressifs constituent un problème majeur de santé publique puisqu’ils affectent plus de 350 millions de personnes dans le monde. La plupart des médicaments antidépresseurs prescrits actuellement ciblent les systèmes monaminergiques centraux. Cependant, ces molécules ont un délai d’action de plusieurs semaines et produisent des effets secondaires substantiels, souvent responsable de l’arrêt du traitement. De plus, un pourcentage non négligeable de patients ne répond que partiellement ou négativement à ces traitements. C’est pourquoi le développement de nouvelles molécules antidépressives constitue un axe majeur de recherche en psychopharmacologie. Le 3β-methoxyprégnénolone (MAP4343), un neurostéroide de synthèse, constitue une nouvelle molécule dont l’efficacité antidépressive a été récemment établie dans un modèle d’isolement social chez le rat. Le mode d’action du MAP4343 serait différent de celui des antidépresseurs conventionnels, puisqu’il a été montré in vitro qu’il pouvait se lier à la protéine associée aux microtubules de type 2 (MAP2) pour ainsi modifier la fonction microtubulaire, ce qui, in fine, favoriserait la plasticité cérébrale.L’objectif de cette thèse est de consolider les preuves de l’efficacité antidépressive du MAP4343 et d’élucider les mécanismes d’action cellulaires associés à son effet pharmacologique. Pour cela, nous avons utilisé un modèle animal, de dépression à savoir le Toupaye de Belanger (toupaia belangeri) soumis au stress psychosocial chronique qui développe des troubles comportementaux, fonctionnels et hormonaux similaires à ceux observés chez les patients dépressifs.Chez le Toupaye, l’administration chronique de MAP4343 (50 mg/kg/jour ; per os) pendant quatre semaines permet d’inhiber la diminution de l’activité locomotrice et le comportement d’évitement induit par le stress. De plus, les altérations physiologiques comme la diminution du poids corporel, l’hyperthermie ou encore les troubles du sommeil sont enrayés par le traitement au MAP4343. Enfin, la molécule agit en inhibant partiellement l’hyperactivation de l’axe adreno-corticotrope. Les mesures dans l’hippocampe de l’expression des isoformes de l’α-tubuline, élément constitutif des microtubules, montrent une diminution de l’α-tubuline tyrosinée, une isoforme plus abondante dans des microtubules néoformés. Ce phénomène n’est pas renversé par le MAP4343. Cependant, le stress chronique induit une réduction de l’expression de la forme acétylée de l’α-tubuline, un phénomène qui serait plus tardif lors d’une altération de la fonction microtubulaire. De façon intéressante, le MAP4343 permet de prévenir cette baisse de l’acétylation. Ce travail de thèse démontre un effet antidépresseur robuste du MAP4343, confirmant ainsi une première étude réalisée auparavant chez le rat. Son efficacité peut se maintenir lors d’un traitement prolongé chez le Toupaye. Cette molécule constituerait ainsi une nouvelle classe d’antidépresseurs ayant comme cible potentielle le système microtubulaires. Des expériences complémentaires seront nécessaires afin de préciser le mode d’action du MAP4343 sur les fonctions neuronales. / Depressive disorders affect more than 350 million people worlwide generating major public health. Most of the antidepressant drugs currently used target monaminergic systems. However, the onset of action of these drugs is delayed for several weeks and they produce important side effects responsible for the discontinuation of treatment. Furthermore, a large rate of patients responds poorly or not at all to this kind of treatment. Accordingly, the development of new antidepressant drugs constitutes a major axis of psychopharmacology research. 3ß-methoxypregnenolone (MAP4343) is a new synthetic neurosteroid whose antidepressant efficacy was recently established in a rat model of social isolation. The mechanism of action of MAP4343 is very likely different from that of conventional antidepressants, as it was shown in vitro that this compound can bind the type 2 microtubule associated protein (MAP2) and may promote in fine the neuronal plasticity. The objective of this thesis is to further demonstrate the antidepressant efficacy of MAP4343 and to elucidate the cellular mechanisms associated to its pharmacological effect. For this purpose, we used one animal models of depression: tree shrews (toupaia belangeri) subjected to a chronic psychosocial stress. Stressed tree shrews develop behavioral, functional and hormonal alterations similar to those observed in the depressive patients. Chronic administration (four weeks) of MAP4343 (50 mg / kg / day) inhibits both the decrease of locomotor activity and the avoidance behavior induced by chronic stress. Furthermore, physiological changes such as hyperthermia or sleep disorders are also reversed by MAP4343 treatment. Finally, the molecule acts by partially inhibiting the stress-induced hyper-activation of hypothalamo-pituitary-adrenal axis. The quantitative study of post-translational modifications of α-tubulin (a major component of microtubules) in the hippocampus shows a decrease of tyrosinated α-tubulin, a dynamic microtubules marker. This phenomenon is not reversed by MAP4343 treatment. However, chronic stress exposure decreases the expression of acetylated α-tubulin, a later phenomenon occurring during microtubular alteration. Interestingly, MAP4343 prevents this decrease. To conclude, this thesis demonstrates a strong antidepressant effect of MAP4343, reproducible in one relevant and translational animal model of depression, thus confirming a previous study realized in an isolated rat model. The efficacy of this compound is observed from the first day of treatment in the rat and persists during a prolonged treatment. This molecule belongs to a new class of antidepressants potentially targeting the microtubular system. Additional experiments will be necessary to well understand the mechanism of action of the MAP4343 on neuronal functions.

The small mammal population of a restricted study area was live-trapped on the University farm at Western Kentucky University from November 1984 through November 1985. A total of 1800 trap-nights yielded 81 different individuals representing five species. Members of the genera Peromyscus and Microtus were the dominant individuals representing over 90% of the total. Also caught were Mus musculus and Blarina brevicauda. The members of the two major genera were examined for population size and dynamics. In addition, a statistical analysis was carried out on the randomness of the location of the home ranges. This analysis gave evidence that the Peromyseus population was centered primarily in the ecotone between field and forest while Microtus was centered exclusively in the field habitat. In addition, the absence or near absence of Microtus for part of the year allowed the Peromyscus population to expand into the field for a short time. Finally, the year long study revealed a characteristic population cycle for each major species due to a combination of reproductive rates, feeding habits and decimation by predation.

Since the 19th century the remains of Quaternary mammals were an important source of data for reconstructing past environmental conditions. I tested two basic assumptions that underlie Quaternary vertebrate paleoecology. The first assumption is that fossils mammals can be identified reliably to species. The second assumption is that correlations established between extant mammals and environmental parameters can be used to interpret reliably the paleoenvironment from the latest Pleistocene. Incorrect specimen identifications could lead to errors in paleoecologic interpretations. I explicitly tested an alternative to the traditional approach to identification by identifying fossil shrews based on apomorphies. My results indicated that some traditional characters are useful for identification, but only complete specimens with a combination of characters can be identified to species. This indicates that previous authors who identified shrews to species did not compare them to the full diversity of species. I tested the reliability of cenograms and species-richness models as approaches for the reconstruction of environmental conditions in the past. I used faunal data from Hall’s Cave, Kerr County, Texas to construct cenograms and species-richness models and compared the results to independent paleoclimate proxies. Neither species-richness models nor cenograms agree with paleoenvironmental reconstructions based on proxy data from the Late Pleistocene and Holocene. Cenograms and species-richness models are unreliable and fraught with problems, and both approaches should be abandoned as tools for paleoecological reconstruction. To test for potential geographic bias in the identification of Quaternary fossils I developed a GIS (geographic information systems) database of Quaternary paleontological sites within Texas. I was able to show that the identification of species of fossil soricids, heteromyids, Odocoileus, and Spilogale was influenced by geography. Those fossils should be treated as generic identifications until they are re-evaluated against the full diversity of species. Utilizing GIS I also developed a method of paleoecological analysis. My analysis showed that the environmental conditions found today in Texas might not be limiting the current range of shrews. Based on the known geographic range of shrew fossils, other ecological factors besides environmental conditions are shaping the current distribution of shrews. / text

Endothermy in birds and mammals is invariably associated with homeothermy. However, homeothermy can only be maintained if sufficient energy is obtained to meet the animals' maintenance budget. In mammals, daily torpor and hibernation have evolved to conserve energy when energy inputs from the environment are insufficient to meet maintenance requirements. Several studies have suggested that daily torpor and hibernation do not represent distinct physiological responses but are components of a continuum of heterothermy. Under laboratory conditions, even within phylogenetically ancient eutherian mammals, such as elephant shrews, it is unclear whether daily torpor or hibernation is used. Furthermore, an interpretation of the torpor patterns observed under laboratory conditions is complicated by the fact that torpor patterns often differ between laboratory and free-ranging conditions. Within the more recent mammal lineages, torpor has been observed in strepsirrhine primates. The occurrence of torpor in strepsirrhines is interesting as it pertains to arguments relating to the colonization of Madagascar by strepsirrhine primates as well as implications for human physiology. The first aim of this study was to investigate and quantify parameters that characterize torpor in a phylogenetically ancient eutherian mammal (Macroscelidae: Elephantulus myurus) under free-ranging conditions. This was done mainly to resolve whether daily torpor and hibernation were physiologically discrete responses. The second aim was to investigate torpor occurrence in a more recently evolved eutherian mammal (Primates: Galago moholi). The objective was to gain insights into the phylogenetic distribution of torpor and to provide a physiological verification of torpor occurrence in a mainland strepsirrhine relative to arguments about the colonization of Madagascar. I measured body temperatures in three monthly cycles between May 2001 - May 2002 in 22 free-ranging E. myurus. I recorded a total of 467 torpor bouts throughout the study period. The elephant shrews were capable of daily torpor throughout the year, with torpor most prevalent during winter and correlated with ambient temperature, photoperiod and invertebrate abundance. Only two torpor bouts were observed during summer. I suggest that although torpor use was most prevalent during winter, summer torpor might also be important for energy conservation in this species during drought years. This highlights the need for long-term physiological data in free-ranging animals. The mean torpor Tbmin and the mean bout length for the whole year were in the range expected for daily heterotherms. However, there was some marginal overlap with hibernation characteristics; a few torpor bouts were longer than 24 hrs in duration indicating that the animals were capable of opportunistically extending torpor bouts longer than 24 hours in response to unpredictable energetic shortfalls. Tbmin also decreased below 10°C. However, a consideration of behavioural and ecological factors argues against hibernation in E. myurus. Instead, these results support the idea of a physiological continuum for heterothermy. A return to normothermic body temperatures requires considerable energy expenditure, and this is perceived to be one of the major disadvantages of torpor. E. myurus offset the high cost of arousal from low body temperatures by using exogenous passive heating. This is achieved by coupling of the timing of arousal with ambient temperature cycles. Laboratory studies that quantify torpor energetics are usually conducted under constant temperature conditions and are likely to underestimate the energetic benefits accrued through the use of ambient temperature cycles during arousal. Torpor is often displayed during the animal's rest phase. However, nocturnal small mammals that utilize passive heating to assist arousal from torpor may enter torpor during the nighttime, thus effectively advancing the onset of the rest phase. I investigated the functional significance of daily and seasonal rhythms of body temperature in normothermic and torpid free-ranging E. myurus. Daily patterns of Tb, in normothermic E. myurus suggested polyphasic Tb patterns that nevertheless indicated a rest phase coincident with the daytime. I suggested that the principal benefit of a flexible daily rhythm of Tb, is that it facilitated torpor use during the nighttime and arousal by passive exogenous heating using ambient temperature cycles. It has been suggested that the evolution of endothermy precluded the need for homeothermic mammals to be sensitive to Ta cycles because they could maintain physiological function despite fluctuations in the ambient temperature. Elephant shrews utilize passive heating and provide excellent models with which to investigate whether mammals can entrain their body temperature rhythms to ambient temperature cycles. I experimentally tested whether food restricted E. myurus can entrain torpor cycles to shifts in the Ta cycle while holding the light-dark cycle constant. Food restriction and short photoperiod were only sufficient to induce torpor in E. myurus if photoperiod and Ta, cycles are in phase with each other. Shifting the cold T, into the photophase prevented the expression of torpor. I concluded that the body temperature rhythm is most probably tightly coupled with the photoperiod cycle and that although Ta and photoperiod usually act synergistically in nature, photoperiod is probably the stronger zeitgeber. The evolution of endothermy is thought to have been facilitated by the advent of endothermic energy sources such as brown adipose tissue (BAT), the principal site of nonshivering thermogenesis (NST). Rock elephant shrews are amongst the smallest members of the Afrotheria, the most basal of the eutherian lineage. I determined whether the phylogenetic placement of E. myurus and reliance on passive heating might result in a decreased capacity for NST relative to other eutherians. I investigated the capacity for NST in winter acclimated E. myurus by measuring the thermogenic response to noradrenalin (NA) injection. I used phylogenetically independent analyses to compare E. myurus NST capacity with other eutherians. E. myurus had an NST capacity that was no different from other eutherian mammals. Although they displayed a NST capacity that was 74% of that expected on the basis of body mass, this value was not significantly different from phylogenetically independent allometric predictions. Although heterothermy is almost always considered in the context of how the environment affects function , its use may offer insights into topics such as island biogeography and species dispersal. For example, there have been suggestions that heterothermy might have played an important role in the successful colonization of Madagascar by strepsirrhine primates. To my knowledge no studies exist as yet that provide a physiological verification of this suggestion. Currently no data exist on thermoregulation and heterothermy in any free-ranging African strepsirrhines. The lesser bushbaby, Galago moholi, is a small nocturnal strepsirrhine primate that experiences severe winters and drastic food reduction during winter and is a candidate employer of torpor. I measured body temperatures of 11 free-ranging lesser bushbabies, Galago moholi, captured at different times between February 2002 - September 2003. I did not record any incidents of heterothermy throughout the study period. Why does G. moholi not employ heterothermy? I consider several alternatives; phylogenetic placement, physiological and ecological factors that might preclude the use of torpor in this species. I suggest that the breeding pattern observed in G. moholi obviates torpor use whilst increasing fecundity, which would be adaptive if the animals are confronted with high predation risks. Much is currently known about the advantages of torpor use. This study highlights the need to consider and investigate those physiological, ecological and phylogenetic factors that might constrain species from utilizinq heterothermy. Furthermore, this study highlights the potential for thermoregulatory studies to offer insights into topics as widely separated as evolution of endothermy to species dispersal and island biogeography. / Thesis (Ph.D.)-University of KwaZulu-Natal, Pietermaritzburg, 2005.

William Shakespeare's play, The Taming of the Shrew has a varied and interesting stage history. Beginning with Fletcher's The Tamer Tarn'd (1633), a sequel to Shakespeare, there have been many adaptations of the plot in farce, opera and poetic drama, including an American musical comedy. This thesis will follow the stage history of The Taming of the Shrew, focussing on the dramatic development and treatment of the heroine, Katherine. Shakespeare's shrew, Katherine, is much more than a traditional shrew stereotype. Her dramatic presentation in language and action has enough depth and subtlety to provoke much conflicting criticism and interpretation. What motivates her anger? Why is she physically abusive? Is she subdued, tamed or reeducated? Enough clues are present in the play to provide for interesting debate. The first part of the thesis is concerned with examining Shakespeare's dramatic concept of the shrew to establish the scope and range of Katherine's personality and her response to Petruchio's taming tricks. In later versions of the play, the character of Katherine receives a variety of dramatic treatments. Some playwrights reduce Katherine's dramatic function to a mere outline. Others accentuate her physically abusive and sharp-tongued qualities. Yet another variation is a softening of the shrewish disposition to allow for a sentimental treatment of shrew conditioning. The dramatic vigour of the shrew character is constant, but variations in plot, language and thematic idea result in very different and entertaining shrew types. This stage history of The Taming of the Shrew as it relates to the heroine, Katherine, includes an analysis of the following plays. The Tamer Tarn'd (1633), a sequel by John Fletcher serves to comment on Shakespeare's Kate by direct allusion and by dramatic contrast. Sauny the Scot (1667) is a bastardised Restoration version in which the shrew is a farcical stereotype who must suffer extensive physical humiliation for her excessive displays of nastiness. Catherine and Petruohio (1756) is David Garrick's miniature version of Shakespeare which stresses the farce, simplifying the play and the dramatic impact of Catherine. John Tobin's The Honeymoon (1805) is a poetic attempt to re-create The Shrew. The heroine in this play suffers the sin of pride, but is won over to domesticity and humility by love and rural surroundings provided by a gentle tamer. The thesis also considers the nineteenth century attempts to revive the Shakespeare original which struggled unsuccessfully with the popularity of the Garrick version. Some of the musical adaptations of The Shrew provide a rich variety of shrew heroines in very different settings. Included are a ballad opera, A Cure for a Scold (1735), a German opera by Hermann Goetz, The Taming of the Shrew (1878), and a modern musical comedy version, Kiss Me Kate (1948). These adaptations and variant versions provide a veritable school of Katherines. The streak of genius in Shakespeare's dramatic idea of a shrew, who, even in the realm of farce is seen as a human being with the capacity to feel, change and grow, becomes very strongly apparent as Shakespeare's Kate is measured against the shrew heroines in these derivative plays. The contrasting shrew types, though interesting and pleasing in their own way, never quite acquire the stature, poise, wit, intelligence and humour which characterise Shakespeare's attractive Kate. For Kate's civilising and learning encounter with Petruchio is not the brutalising, punitive or subjugating ritual of tradition; amidst the slapstick of farce, Kate, with her Petruchio, provides a unique variation of the shrew heroine. She is not conquered. She changes herself. This is her distinction and her strength and the mark of Shakespeare's human touch. / Arts, Faculty of / English, Department of / Graduate

The identification of non-random species composition patterns predicted by assembly rules is a central theme in community ecology. Based on life history characteristics, species composition patterns of rodents and shrews should be consistent with predictions from nestedness rather than competition hypotheses. This study investigated the seasonal changes in rodent and shrew assemblages in eleven savanna vegetation types in a protected reserve in South Africa. Rodents and shrews were sampled between 2009 and 2010 at Phinda Private Game Reserve (PPGR), KwaZulu-Natal. Sample-based rarefaction curves showed that rodent and shrew abundance and richness varied among seasons and vegetation types. Species richness estimators indicated that inventories for rodents (80%) and shrews (100%) were fairly complete. Null-model analyses found no evidence that species co-occurrence patterns in the reserve were non-random with respect to predictions from Diamond’s Assembly rules, niche limitation hypothesis and nestedness hypothesis. I also investigated seasonal changes in species richness and abundance of rodent and shrew assemblages on cattle, pineapple and former cattle farms surrounding PPGR, and used cluster analyses to compare the species composition of rodents and shrews at farm and PPGR study sites. Small mammal assemblages exhibited a heterogeneous distribution and species composition patterns changed between seasons. Sample-based rarefaction curves showed that rodent and shrew abundance and richness varied among seasons and study sites. Species richness estimators indicated that inventories for the rodents (91%) and shrews (100%) on the farms were essentially complete. Rodent and shrew species composition patterns did not group study sites according to land use, nor could species composition patterns be explained by vegetation characteristics. My results suggest that complex biotic and abiotic processes other than competition, nestedness, land use and vegetation characteristics operate at different spatial and temporal scales to structure rodent and shrew assemblages. / Thesis (M.Sc.)-University of KwaZulu-Natal, Westville, 2013.

Le cannabis produit de nombreux effets psychologiques et physiologiques sur le corps humain. Les molécules contenues dans cette plante, désignées comme « phytocannabinoïdes », activent un système endogène qu’on appelle le système endocannabinoïde (eCB). Les effets de la consommation de cannabis sur la vision ont déjà été décrits sans cependant de formulation sur les mécanismes sous-jacents. Ces résultats comportementaux suggèrent, malgré tout, la présence de ce système eCB dans le système visuel, et particulièrement dans la rétine. Cette thèse vise donc à caractériser l’expression, la localisation et le rôle du système eCB dans la rétine du singe vervet, une espèce animale ayant un système visuel semblable à celui de l’humain. Nous avons mis au point un protocole expérimental d’immunohistochimie décrit dans l’article apparaissant dans l’Annexe I que nous avons utilisé pour répondre à notre objectif principal. Dans une première série de quatre articles, nous avons ainsi caractérisé l’expression et la localisation de deux récepteurs eCBs reconnus, les récepteurs cannabinoïdes de type 1 (CB1R) et de type 2 (CB2R), et d’un 3e présumé récepteur aux cannabinoïdes, le récepteur GPR55. Dans l’article 1, nous avons démontré que CB1R et une enzyme clé de ce système, la fatty acid amide hydrolase (FAAH), sont exprimés dans les parties centrale et périphérique de la rétine, et abondamment présents dans la fovéa, une région où l’acuité visuelle est maximale. Dans l’article 2, nous avons localisé le CB2R dans des cellules gliales de la rétine : les cellules de Müller et nous avons proposé un modèle sur l’action de cette protéine dans la fonction rétinienne faisant appel à une cascade chimique impliquant les canaux potassiques. Dans l’article 3, nous avons observé le GPR55 exclusivement dans les bâtonnets qui sont responsables de la vision scotopique et nous avons soumis un deuxième modèle de fonctionnement de ce récepteur par le biais d'une modulation des canaux calciques et sodiques des bâtonnets. Vu que ces 3 récepteurs se retrouvent dans des cellules distinctes, nous avons suggéré leur rôle primordial dans l’analyse de l’information visuelle au niveau rétinien. Dans l’article 4, nous avons effectué une analyse comparative de l’expression du système eCB dans la rétine de souris, de toupayes (petits mammifères insectivores qui sont sont considérés comme l’étape intermédiaire entre les rongeurs et les primates) et de deux espèces de singe (le vervet et le rhésus). Ces résultats nous ont menés à présenter une hypothèse évolutionniste quant à l’apparition et à la fonction précise de ces récepteurs. Dans les articles subséquents, nous avons confirmé notre hypothèse sur le rôle spécifique de ces trois récepteurs par l’utilisation de l’électrorétinographie (ERG) après injection intravitréenne d’agonistes et d’antagonistes de ces récepteurs. Nous avons conclu sur leur influence indéniable dans le processus visuel rétinien chez le primate. Dans l’article 5, nous avons établi le protocole d’enregistrement ERG normalisé sur le singe vervet, et nous avons produit un atlas d’ondes ERG spécifique à cette espèce, selon les règles de l’International Society for Clinical Electrophysiology of Vision (ISCEV). Les patrons électrorétinographiques se sont avérés semblables à ceux de l’humain et ont confirmé la similarité entre ces deux espèces. Dans l’article 6, nous avons démontré que le blocage de CB1R ou CB2R entraine une modification de l’électrorétinogramme, tant au niveau photopique que scotopique, ce qui supporte l’implication de ces récepteurs dans la modulation des ondes de l’ERG. Finalement, dans l’article 7, nous avons confirmé le modèle neurochimique proposé dans l’article 3 pour expliquer le rôle fonctionnel de GPR55, en montrant que l’activation ou le blocage de ce récepteur, respectivement par un agoniste (lysophosphatidylglucoside, LPG) ou un antagoniste (CID16020046), entraine soit une augmentation ou une baisse significative de l’ERG scotopique seulement. Ces données, prises ensemble, démontrent que les récepteurs CB1R, CB2R et GPR55 sont exprimés dans des types cellulaires bien distincts de la rétine du singe et ont chacun un rôle spécifique. L’importance de notre travail se manifeste aussi par des applications cliniques en permettant le développement de cibles pharmacologiques potentielles dans le traitement des maladies de la rétine. / Cannabis produces a range of psychological and physiological effects on the human body. Cannabinoids are the chemical compounds found in cannabis that activate an endogenous system, termed the endocannabinoid (eCB) system. Reports made in the 1970s have noted that cannabis consumption affects vision. It is therefore suggested that the eCB system is present in the visual system, particularly in the retina. This thesis aims at characterizing the expression, localization, and role of the eCB system in the vervet monkey retina. This animal model has a similar visual system as humans. Using immunohistochemistry methods presented in the article of Annexe I, we have established an experimental protocol to answer our goal. In the first series of four articles, we have characterized the expression and localization of the cannabinoid receptor 1 (CB1R), cannabinoid receptor 2 (CB2R), and the putative cannabinoid receptor GPR55. In Article 1, we have demonstrated that CB1R and a key enzyme of this system, FAAH (fatty acid amide hydrolase), are expressed in the central and peripheral retina, but heavily present in the fovea, the retinal region responsible for high acuity vision. In Article 2, we have localized CB2R in the glial Müller cells and hypothesized a possible mechanism of action of CB2R involving potassium buffering. In Article 3, we found that GPR55 is exclusively expressed in rods and have proposed its role through the modulation of calcium and sodium channels in rods. Given that these three receptors are segregated in the vervet monkey retina, we suggested that they might have distinct roles in retinal physiology. In Article 4, we reported a comparative analysis of the expression of the eCB system components in the retina of rodents, tree shrews (small mammals considered as early primates), and monkeys. This paper provides evidence that the eCB system is differently expressed in the retina of these mammals and suggests a distinctive role of eCBs in visual processing. In the subsequent series of three articles, we confirmed their suggested roles in the retina by using electroretinography (ERG) and intravitreal injections of agonist and antagonist of these receptors. We concluded that they indeed play important roles in the retina. In Article 5, we developed a standard protocol for ERG testing in our animal model and have published an ERG atlas with normalized amplitudes and latency values similar to that of humans, following the guidelines of the International Society for Clinical Electrophysiology of Vision. In Article 6, we showed that blockade of CB1R or CB2R with specific antagonists modifies the ERG, both in photopic and scotopic conditions, which confirms the implication of these receptors in normal retinal function. Finally, in Article 7 (expression of GPR55 in rods only), we confirmed the suggest role of GPR55 in rods by showing that activation or blockade of GPR55 with a specific agonist (lysophosphatidylglucoside) or antagonist (CID16020046) increases or decreases the amplitude of the scotopic ERG waveforms. Taken together, these articles demonstrate that CB1R, CB2R, and GPR55 are differentially expressed in the vervet monkey retina and have distinct roles. This work has also clinical relevance in the way that we have discovered new pharmacological targets that can be used for treatment of many retinal diseases.

Insgesamt 1746 Kleinsäuger aus den Familien Muridae (Murinae, Arvicolinae) und Soricidae aus dem Naturschutzgebiet ”Großer Hakel” (Sachsen-Anhalt) und der Tagebaufolgelandschaft ”Phönix-Ost und Rusendorf” Meuselwitz (Thüringen) wurden auf einen Befall mit Capillaria hepatica und Metazestoden von Bandwürmern (Cyclophyllida) untersucht. Das Tiermaterial stammte aus genehmigten faunistischen Untersuchungen aus den Jahren 1993 bis 1997 in Zusammenarbeit mit der Universität Halle und dem Naturkundemuseum "Mauritianum" Altenburg. Alle Mäuse wurden seziert und der Brust- und Bauchraum einschließlich aller Organoberflächen, der Subkutis, des Gehirns und der Leber untersucht. Eine Altersbestimmung der Wirte erfolgte bei den untersuchten Rötelmäusen (Clethrionomys glareolus). Erstmals in Deutschland konnte im Hakel ein stabiles Endemiegebiet von Capillaria hepatica bei Wildmäusen nachgewiesen werden. Die aus dem ”Großen Hakel” stammenden Gelbhals- (Apodemus flavicollis) und Rötelmäuse wiesen Befallshäufigkeiten von 8,5 bzw. 15,1 % auf, die Eizahlen pro Leber lagen zwischen 67 und 3 600 000. Weibliche Mäuse zeigten eine höhere Befallshäufigkeit als männliche Mäuse. Bei den Rötelmäusen konnte ein Anstieg der Befallshäufigkeit von 5,8 % der bis zu 3 Monate alten bis auf 28,6 % der bis zu einem Jahr alten Tiere beobachtet werden. Patente Infektionen waren erst in der Altersgruppe 3-6 Monate nachzuweisen. In dem Untersuchungsgebiet Meuselwitz war Capillaria hepatica bei den untersuchten 1069 Muridae und Soricidae nicht nachweisbar. Eine aktuelle Übersicht der weltweit in 53 Ländern festgestellten 137 Wirtsarten aus 25 Säugetierfamilien von Capillaria hepatica wurde zusammengestellt. Die Familie Muridae stellt mit 83 Arten die bedeutendste Wirtsgruppe dar. Bisher wurde über 56 Capillaria-hepatica-Infektionen beim Menschen (davon 39 Kinder) aus 18 Ländern berichtet. Die Leitsymptome der Erkrankung beim Menschen sind intermittierendes Fieber, Hepatomegalie, Leukozytose mit hochgradiger, persistierender Eosinophilie, Anämie, Hypergammaglobulinämie und Hypoalbuminämie. Die Serumaktivitäten von AST, ALT und LDH sind erhöht. Die Diagnose der zum Teil tödlich verlaufenden Erkrankung ist intra vitam bisher nur durch Leberbiopsie oder Laparotomie möglich. Einzelne Versuche mit serologischen Tests scheinen erfolgversprechend. Die Einzelnachweise von Capillaria hepatica bei Mensch, Hase und Sumpfbiber in Deutschland (Bayern, Sachsen und Sachsen-Anhalt) sind als Hinweise auf bestehende Endemiegebiete zu werten. Aufgrund der weiteren Verbreitung und der diagnostischen Probleme kann von einer höheren Gefährdung des Menschen (insbesondere Kleinkinder) und der Haustiere durch den Zoonoseerreger Capillaria hepatica ausgegangen werden. Bei 10,5 % aller untersuchten Mäuse wurden Metazestoden gefunden. Die Rötelmaus wies insgesamt mit durchschnittlich 23,5 % (Meuselwitz 30,2 %, Hakel 15,1 %) die signifikant höchsten Befallshäufigkeiten mit Metazestoden auf. Insgesamt konnten bei Muridae und Soricidae in Sachsen-Anhalt und Thüringen Metazestoden von 8 Bandwurmgattungen bzw. -arten (Cladotaenia globifera, Mesocestoides spp., T. crassiceps, T. martis martis, T. martis americana, T. mustelae, T. polyacantha, T. taeniaeformis) nachgewiesen werden. Die breiteste Metazestodenfauna mit insgesamt 7 Arten wurde bei der Feldmaus (Microtus arvalis), nur jeweils eine Metazestodenart dagegen bei Brandmaus (Apodemus agrarius), Zwergmaus (Micromys minutus), Feldspitzmaus (Crocidura leucodon) und Waldspitzmaus (Sorex araneus) gefunden. Die Zwergspitzmaus (Sorex minutus) war nicht von Metazestoden befallen. Eine deutliche Wirtsspezifität (Feldmaus) konnte für T.-crassiceps- und T.-polyacantha-Metazestoden festgestellt werden. Im Gebiet Meuselwitz dominierten bei Muridae Metazestoden von T. mustelae (Befallshäufigkeit 9,3 %) sowie von T. martis martis (Befallshäufigkeit 6,4 %), im Hakel von T. martis martis (Befallshäufigkeit 2,5 %) sowie T. mustelae (Befallshäufigkeit 2,2 %). Während in Meuselwitz die höchsten Befallshäufigkeiten mit Metazestoden von T. mustelae (24,7 %) bei der Rötelmaus und von T. martis martis (13 %) bei der Gelbhalsmaus vorlagen, waren im Hakel die Rötelmäuse am häufigsten mit T.-mustelae- (8,2 %) und T.-martis-martis- Metazestoden (4,8 %) befallen. Mit zunehmendem Alter der Rötelmäuse stieg die Befallshäufigkeit mit Metazestoden bei dieser Tierart an. Rötelmäuse unter einem Alter von 2 Monaten waren noch nicht von Metazestoden befallen. Infektionen mit 2 Metazestodenarten traten erstmals bei 4 Monate alten Rötelmäusen auf, bei zwei Tieren im Alter von 9 bzw. 12 Monaten wurden Infektionen mit 3 Metazestodenarten (Cladotaenia globifera + T. martis americana + T. mustelae; Cladotaenia globifera + T. martis martis + T. mustelae) nachgewiesen. Bei insgesamt 10 Muriden konnten Mischinfektionen mit Capillaria hepatica und Metazestoden von Bandwürmern festgestellt werden. Bei Mäusen der Familie Soricidae sind ausschließlich Metazestoden von Cladotaenia globifera gefunden worden. Erstnachweise für Deutschland stellen Funde der Metazestoden von Cladotaenia globifera bei der Feldspitzmaus, T. martis americana bei der Rötelmaus, T. mustelae bei Erd- und Zwergmaus und T. polyacantha bei der Waldmaus dar. Das erste Mal in Europa konnten T.-martis-americana-Metazestoden bei der Feldmaus gefunden werden. Eine wichtige Einflußgröße auf die Metazestodenfauna war das Aufeinandertreffen von End- und Zwischenwirt in bestimmten Biotopen. / The occurrence of Capillaria hepatica and metacestodes of Cyclophillida was investigated in 1746 small mammals of the families Muridae (Murinae, Arvicolinae) and Soricidae from the nature reserve ”Grosser Hakel” (Saxony-Anhalt) and the former open-cast mining area "Phoenix-Ost and Rusendorf" Meuselwitz (Thuringia). The animals came from approved faunistic surveys in co-operation with the University of Halle and the natural history museum ”Mauritianum” Altenburg. All mice were sectioned and the thoracic as well as the abdominal cavity including all organ surfaces, subcutaneous tissue, brain and liver were examined. The age of all bank voles (Clethrionomys glareolus) was determined. In the nature reserve "Grosser Hakel"an stable endemic area of Capillaria hepatica in wild mice could be detected for the first time in Germany. The percentage of yellow-necked mice (Apodemus flavicollis) infected with Capillaria hepatica in that area was 8.5 %, the percentage of bank voles infected with Capillaria hepatica in that area reached 15.1 % respectively. The number of eggs per liver ranged from 67 to 3,600,000. The proportion of infected mice was higher in female than in male mice. In bank voles the frequency of infection increased with age (from 5.8 % in the age of 3 months to 28.6 % in the age of one year). Patent infections were first detected in the age group of 3 to 6 month. No Capillaria hepatica could be found in 1069 Muridae and Soricidae examined in the Meuselwitz area. A current survey of the world-wide occurrence of Capillaria hepatica in 137 hosts of 25 mammal families was prepared. The family of Muridae (with 83 species) is the most important host group. Up to now 56 Capillaria-hepatica-infections in humans (including 39 children) from 18 different countries were reported. Major symptoms in humans are intermittent fever, hepatomegaly, leucocytosis with severe, persistent eosinophilia, anaemia, hypergammaglobulinaemia and hypoalbuminaemia. The serum activities of AST, ALT and LDH are elevated. Intra-vitam diagnosis of this partly lethal disease is only possible by liver biopsy or laparatomy. First serological tests are promising. Sporadic detection of Capillaria hepatica in humans, hares and nutria in Germany (Bavaria, Saxony and Saxony-Anhalt) can be regarded as an indication of existing endemic areas. A higher risk of Capillaria-hepatica-infection in humans (especially in small children) and domestic animals can be assumed on the basis of the wide distribution and the diagnostic problems. Metacestodes were found in 10.5 % of all examined mice. The bank voles showed the significantly highest rate of infection with 23.5 % (Meuselwitz 30.2 % and Hakel 15.1 %). Altogether metacestodes of 8 tapeworm genuses (Cladotaenia globifera, Mesocestoides spp., T. crassiceps, T. martis martis, T. martis americana, T. mustelae, T. polyacantha, T. taeniaeformis) could be detected in Muridae and Soricidae in Saxony-Anhalt and Thuringia. The broadest metacestode-fauna (with 7 species) was found in the common vole (Microtus arvalis). Only one metacestode-species was detected in the stripped field mouse (Apodemus agrarius), the harvest mouse (Micromys minutus), the bicoloured whitetoothed shrew (Crocidura leucodon) and the eurasion common shrew (Sorex araneus). The pygmy shrew (Sorex minutus) was not infected by metacestodes. A distinct host specificity (in the common vole) could be established for T. crassiceps and T. polyacantha. Metacestodes of T. mustelae (infection rate 9.3 %) and T. martis martis (infection rate 6.4 %) dominated in Muridae of the Meuselwitz area. In the Hakel area T. martis martis (infection rate 2.5 %) and T. mustelae (infection rate 2.2 %) dominated as well. Whereas metacestodes of T. mustelae occurred in the bank vole with an infection rate of 24.7 % and T. martis martis in yellow-necked mice with an infection rate of 13.0 % in the Meuselwitz area, T. mustelae occurred in bank voles with an infection rate of 8.2 % and T. martis martis in yellow-necked mice with an infection rate of 4.8 % in the Hakel area. The infection rate of bank voles with metacestodes increased with age. No metacestodes were found in bank voles younger than 2 month of age. Infection with 2 different metacestode-species occurred in bank voles for the first time at the age of 4 month. 3 metacestode-species were found in 2 animals at the age of 9 to 12 months (Cladotaenia globifera + T. martis americana + T. mustelae; Cladotaenia globifera + T. martis martis + T. mustelae). In 10 Muridae occurred a mixed infection with Capillaria hepatica and metacestodes of tapeworms. In mice of the Soricidae-family only metacestodes from Cladotaenia globifera could be found. For the first time in Germany were detected metacestodes of Cladotaenia globifera in the bicoloured whitetoothed shrew, of T. martis americana in bank voles, of T. mustelae in the common field vole and the harvest mouse and of T. polyacantha in the wood mouse. For the first time in Europe T. martis americana-metacestodes could be detected in the common vole. Of high importance to the metacestode-fauna was the encounter of final host and intermediate host in certain biotopes.

Insgesamt 1746 Kleinsäuger aus den Familien Muridae (Murinae, Arvicolinae) und Soricidae aus dem Naturschutzgebiet ”Großer Hakel” (Sachsen-Anhalt) und der Tagebaufolgelandschaft ”Phönix-Ost und Rusendorf” Meuselwitz (Thüringen) wurden auf einen Befall mit Capillaria hepatica und Metazestoden von Bandwürmern (Cyclophyllida) untersucht. Das Tiermaterial stammte aus genehmigten faunistischen Untersuchungen aus den Jahren 1993 bis 1997 in Zusammenarbeit mit der Universität Halle und dem Naturkundemuseum "Mauritianum" Altenburg. Alle Mäuse wurden seziert und der Brust- und Bauchraum einschließlich aller Organoberflächen, der Subkutis, des Gehirns und der Leber untersucht. Eine Altersbestimmung der Wirte erfolgte bei den untersuchten Rötelmäusen (Clethrionomys glareolus). Erstmals in Deutschland konnte im Hakel ein stabiles Endemiegebiet von Capillaria hepatica bei Wildmäusen nachgewiesen werden. Die aus dem ”Großen Hakel” stammenden Gelbhals- (Apodemus flavicollis) und Rötelmäuse wiesen Befallshäufigkeiten von 8,5 bzw. 15,1 % auf, die Eizahlen pro Leber lagen zwischen 67 und 3 600 000. Weibliche Mäuse zeigten eine höhere Befallshäufigkeit als männliche Mäuse. Bei den Rötelmäusen konnte ein Anstieg der Befallshäufigkeit von 5,8 % der bis zu 3 Monate alten bis auf 28,6 % der bis zu einem Jahr alten Tiere beobachtet werden. Patente Infektionen waren erst in der Altersgruppe 3-6 Monate nachzuweisen. In dem Untersuchungsgebiet Meuselwitz war Capillaria hepatica bei den untersuchten 1069 Muridae und Soricidae nicht nachweisbar. Eine aktuelle Übersicht der weltweit in 53 Ländern festgestellten 137 Wirtsarten aus 25 Säugetierfamilien von Capillaria hepatica wurde zusammengestellt. Die Familie Muridae stellt mit 83 Arten die bedeutendste Wirtsgruppe dar. Bisher wurde über 56 Capillaria-hepatica-Infektionen beim Menschen (davon 39 Kinder) aus 18 Ländern berichtet. Die Leitsymptome der Erkrankung beim Menschen sind intermittierendes Fieber, Hepatomegalie, Leukozytose mit hochgradiger, persistierender Eosinophilie, Anämie, Hypergammaglobulinämie und Hypoalbuminämie. Die Serumaktivitäten von AST, ALT und LDH sind erhöht. Die Diagnose der zum Teil tödlich verlaufenden Erkrankung ist intra vitam bisher nur durch Leberbiopsie oder Laparotomie möglich. Einzelne Versuche mit serologischen Tests scheinen erfolgversprechend. Die Einzelnachweise von Capillaria hepatica bei Mensch, Hase und Sumpfbiber in Deutschland (Bayern, Sachsen und Sachsen-Anhalt) sind als Hinweise auf bestehende Endemiegebiete zu werten. Aufgrund der weiteren Verbreitung und der diagnostischen Probleme kann von einer höheren Gefährdung des Menschen (insbesondere Kleinkinder) und der Haustiere durch den Zoonoseerreger Capillaria hepatica ausgegangen werden. Bei 10,5 % aller untersuchten Mäuse wurden Metazestoden gefunden. Die Rötelmaus wies insgesamt mit durchschnittlich 23,5 % (Meuselwitz 30,2 %, Hakel 15,1 %) die signifikant höchsten Befallshäufigkeiten mit Metazestoden auf. Insgesamt konnten bei Muridae und Soricidae in Sachsen-Anhalt und Thüringen Metazestoden von 8 Bandwurmgattungen bzw. -arten (Cladotaenia globifera, Mesocestoides spp., T. crassiceps, T. martis martis, T. martis americana, T. mustelae, T. polyacantha, T. taeniaeformis) nachgewiesen werden. Die breiteste Metazestodenfauna mit insgesamt 7 Arten wurde bei der Feldmaus (Microtus arvalis), nur jeweils eine Metazestodenart dagegen bei Brandmaus (Apodemus agrarius), Zwergmaus (Micromys minutus), Feldspitzmaus (Crocidura leucodon) und Waldspitzmaus (Sorex araneus) gefunden. Die Zwergspitzmaus (Sorex minutus) war nicht von Metazestoden befallen. Eine deutliche Wirtsspezifität (Feldmaus) konnte für T.-crassiceps- und T.-polyacantha-Metazestoden festgestellt werden. Im Gebiet Meuselwitz dominierten bei Muridae Metazestoden von T. mustelae (Befallshäufigkeit 9,3 %) sowie von T. martis martis (Befallshäufigkeit 6,4 %), im Hakel von T. martis martis (Befallshäufigkeit 2,5 %) sowie T. mustelae (Befallshäufigkeit 2,2 %). Während in Meuselwitz die höchsten Befallshäufigkeiten mit Metazestoden von T. mustelae (24,7 %) bei der Rötelmaus und von T. martis martis (13 %) bei der Gelbhalsmaus vorlagen, waren im Hakel die Rötelmäuse am häufigsten mit T.-mustelae- (8,2 %) und T.-martis-martis- Metazestoden (4,8 %) befallen. Mit zunehmendem Alter der Rötelmäuse stieg die Befallshäufigkeit mit Metazestoden bei dieser Tierart an. Rötelmäuse unter einem Alter von 2 Monaten waren noch nicht von Metazestoden befallen. Infektionen mit 2 Metazestodenarten traten erstmals bei 4 Monate alten Rötelmäusen auf, bei zwei Tieren im Alter von 9 bzw. 12 Monaten wurden Infektionen mit 3 Metazestodenarten (Cladotaenia globifera + T. martis americana + T. mustelae; Cladotaenia globifera + T. martis martis + T. mustelae) nachgewiesen. Bei insgesamt 10 Muriden konnten Mischinfektionen mit Capillaria hepatica und Metazestoden von Bandwürmern festgestellt werden. Bei Mäusen der Familie Soricidae sind ausschließlich Metazestoden von Cladotaenia globifera gefunden worden. Erstnachweise für Deutschland stellen Funde der Metazestoden von Cladotaenia globifera bei der Feldspitzmaus, T. martis americana bei der Rötelmaus, T. mustelae bei Erd- und Zwergmaus und T. polyacantha bei der Waldmaus dar. Das erste Mal in Europa konnten T.-martis-americana-Metazestoden bei der Feldmaus gefunden werden. Eine wichtige Einflußgröße auf die Metazestodenfauna war das Aufeinandertreffen von End- und Zwischenwirt in bestimmten Biotopen. / The occurrence of Capillaria hepatica and metacestodes of Cyclophillida was investigated in 1746 small mammals of the families Muridae (Murinae, Arvicolinae) and Soricidae from the nature reserve ”Grosser Hakel” (Saxony-Anhalt) and the former open-cast mining area "Phoenix-Ost and Rusendorf" Meuselwitz (Thuringia). The animals came from approved faunistic surveys in co-operation with the University of Halle and the natural history museum ”Mauritianum” Altenburg. All mice were sectioned and the thoracic as well as the abdominal cavity including all organ surfaces, subcutaneous tissue, brain and liver were examined. The age of all bank voles (Clethrionomys glareolus) was determined. In the nature reserve "Grosser Hakel"an stable endemic area of Capillaria hepatica in wild mice could be detected for the first time in Germany. The percentage of yellow-necked mice (Apodemus flavicollis) infected with Capillaria hepatica in that area was 8.5 %, the percentage of bank voles infected with Capillaria hepatica in that area reached 15.1 % respectively. The number of eggs per liver ranged from 67 to 3,600,000. The proportion of infected mice was higher in female than in male mice. In bank voles the frequency of infection increased with age (from 5.8 % in the age of 3 months to 28.6 % in the age of one year). Patent infections were first detected in the age group of 3 to 6 month. No Capillaria hepatica could be found in 1069 Muridae and Soricidae examined in the Meuselwitz area. A current survey of the world-wide occurrence of Capillaria hepatica in 137 hosts of 25 mammal families was prepared. The family of Muridae (with 83 species) is the most important host group. Up to now 56 Capillaria-hepatica-infections in humans (including 39 children) from 18 different countries were reported. Major symptoms in humans are intermittent fever, hepatomegaly, leucocytosis with severe, persistent eosinophilia, anaemia, hypergammaglobulinaemia and hypoalbuminaemia. The serum activities of AST, ALT and LDH are elevated. Intra-vitam diagnosis of this partly lethal disease is only possible by liver biopsy or laparatomy. First serological tests are promising. Sporadic detection of Capillaria hepatica in humans, hares and nutria in Germany (Bavaria, Saxony and Saxony-Anhalt) can be regarded as an indication of existing endemic areas. A higher risk of Capillaria-hepatica-infection in humans (especially in small children) and domestic animals can be assumed on the basis of the wide distribution and the diagnostic problems. Metacestodes were found in 10.5 % of all examined mice. The bank voles showed the significantly highest rate of infection with 23.5 % (Meuselwitz 30.2 % and Hakel 15.1 %). Altogether metacestodes of 8 tapeworm genuses (Cladotaenia globifera, Mesocestoides spp., T. crassiceps, T. martis martis, T. martis americana, T. mustelae, T. polyacantha, T. taeniaeformis) could be detected in Muridae and Soricidae in Saxony-Anhalt and Thuringia. The broadest metacestode-fauna (with 7 species) was found in the common vole (Microtus arvalis). Only one metacestode-species was detected in the stripped field mouse (Apodemus agrarius), the harvest mouse (Micromys minutus), the bicoloured whitetoothed shrew (Crocidura leucodon) and the eurasion common shrew (Sorex araneus). The pygmy shrew (Sorex minutus) was not infected by metacestodes. A distinct host specificity (in the common vole) could be established for T. crassiceps and T. polyacantha. Metacestodes of T. mustelae (infection rate 9.3 %) and T. martis martis (infection rate 6.4 %) dominated in Muridae of the Meuselwitz area. In the Hakel area T. martis martis (infection rate 2.5 %) and T. mustelae (infection rate 2.2 %) dominated as well. Whereas metacestodes of T. mustelae occurred in the bank vole with an infection rate of 24.7 % and T. martis martis in yellow-necked mice with an infection rate of 13.0 % in the Meuselwitz area, T. mustelae occurred in bank voles with an infection rate of 8.2 % and T. martis martis in yellow-necked mice with an infection rate of 4.8 % in the Hakel area. The infection rate of bank voles with metacestodes increased with age. No metacestodes were found in bank voles younger than 2 month of age. Infection with 2 different metacestode-species occurred in bank voles for the first time at the age of 4 month. 3 metacestode-species were found in 2 animals at the age of 9 to 12 months (Cladotaenia globifera + T. martis americana + T. mustelae; Cladotaenia globifera + T. martis martis + T. mustelae). In 10 Muridae occurred a mixed infection with Capillaria hepatica and metacestodes of tapeworms. In mice of the Soricidae-family only metacestodes from Cladotaenia globifera could be found. For the first time in Germany were detected metacestodes of Cladotaenia globifera in the bicoloured whitetoothed shrew, of T. martis americana in bank voles, of T. mustelae in the common field vole and the harvest mouse and of T. polyacantha in the wood mouse. For the first time in Europe T. martis americana-metacestodes could be detected in the common vole. Of high importance to the metacestode-fauna was the encounter of final host and intermediate host in certain biotopes.