The first part of my thesis involves an investigation into mechanisms underlying the presynaptic regulation of transmitter release from myelinated hindlimb sensory afferents in rodents. The central hypothesis is that in addition to chemical transmission in spinal neuronal networks, electrical synapses formed by connexins are critically involved in presynaptic inhibition of large diameter sensory afferents. Subsequent sections of the thesis present a detailed examination of the distribution of connexins in the rodent spinal cord with a particular emphasis on the neuronal connexin, Cx36. Connexin36 (Cx36) is widely believed to be the protein forming the neuronal gap junctions that create electrical synapses between mammalian neurons in many areas of the central nervous system (Condorelli et al 1998). The first part of thesis concerns a previously unknown role of neuronal connexins in interneurone pathways involved in presynaptic control of synaptic transmission in the lumbar spinal cord of rodents. As far as we are aware, the idea that electrical contacts between spinal neurons contribute to spinal presynaptic inhibition is a novel hypothesis. Evidence will be presented: 1) that Cx36 is present in regions of the spinal cord containing interneurons involved in presynaptic inhibition, 2) that the lack of Cx36 in Cx36-/- knockouts mice results in a severe impairment of presynaptic inhibition, and 3) that blocking gap junctions pharmacologically in wild type mice impairs presynaptic inhibition. The exploration of this hypothesis will involve a combination of electrophysiological and immunohistochemical approaches in juvenile wild-type and knockout mice lacking Cx36, as well as immunohistochemical observations in adult rodents. This first section of the thesis begins with the development of a preparation in which several measures of presynaptic inhibition described in the in vivo adult cat preparation can be examined in vitro in young mice. The following sections of the thesis describe the distribution and features of Cx36 on neurons in mice and rats of different ages in four parts. The first will show that Cx36 is the only connexin associated with spinal neurons and refutes claims in the literature about the existence of a variety of connexions on spinal neurons. The second part will show that while gap junctions between some spinal neurons are only a transient developmental phenomenon, they persist in abundance in adult animals. The third part will present evidence of a previously unsuspected III association of Cx36 gap junctions at the chemical synapse between muscle afferent fibres and motoneurons. Specifically, an association between Cx36 and the glutamate transporter used in primary afferents, Vglut1 will be described. To our knowledge these results are the first to suggest the existence of mixed (electrical and chemical) synapses between primary afferents and motoneurons in the mature mammalian spinal cord. The final part of the thesis will describe the presence of Cx36 gap junctions on adult sacral motoneurons involved in control of sexual, urinary and defecation functions in the rodent.

The first part of my thesis involves an investigation into mechanisms underlying the presynaptic regulation of transmitter release from myelinated hindlimb sensory afferents in rodents. The central hypothesis is that in addition to chemical transmission in spinal neuronal networks, electrical synapses formed by connexins are critically involved in presynaptic inhibition of large diameter sensory afferents. Subsequent sections of the thesis present a detailed examination of the distribution of connexins in the rodent spinal cord with a particular emphasis on the neuronal connexin, Cx36. Connexin36 (Cx36) is widely believed to be the protein forming the neuronal gap junctions that create electrical synapses between mammalian neurons in many areas of the central nervous system (Condorelli et al 1998). The first part of thesis concerns a previously unknown role of neuronal connexins in interneurone pathways involved in presynaptic control of synaptic transmission in the lumbar spinal cord of rodents. As far as we are aware, the idea that electrical contacts between spinal neurones contribute to spinal presynaptic inhibition is a novel hypothesis. Evidence will be presented: 1) that Cx36 is present in regions of the spinal cord containing interneurones involved in presynaptic inhibition, 2) that the lack of Cx36 in Cx36-/- knockouts mice results in a severe impairment of presynaptic inhibition, and 3) that blocking gap junctions pharmacologically in wild type mice impairs presynaptic inhibition. The exploration of this hypothesis will involve a combination of electrophysiological and immunohistochemical approaches in juvenile wild-type and knockout mice lacking Cx36, as well as immunohistochemical observations in adult rodents. This first section of the thesis begins with the development of a preparation in which several measures of presynaptic inhibition described in the in vivo adult cat preparation can be examined in vitro in young mice. The following sections of the thesis describe the distribution and features of Cx36 on neurones in mice and rats of different ages in four parts. The first will show that Cx36 is the only connexin associated with spinal neurons and refutes claims in the literature about the existence of a variety of connexions on spinal neurons. The second part will show that while gap junctions between some spinal neurons are only a transient developmental phenomenon, they persist in abundance in adult animals. The third part will present evidence of a previously unsuspected III association of Cx36 gap junctions at the chemical synapse between muscle afferent fibres and motoneurones. Specifically, an association between Cx36 and the glutamate transporter used in primary afferents, Vglut1 will be described. To our knowledge these results are the first to suggest the existence of mixed (electrical and chemical) synapses between primary afferents and motoneurones in the mature mammalian spinal cord. The final part of the thesis will describe the presence of Cx36 gap junctions on adult sacral motoneurones involved in control of sexual, urinary and defecation functions in the rodent.

Modulation of a synaptic transmission in the spinal cord dorsal horn plays a key role in nociceptive signalling, especially in states of pathological pain. The goal of this study was to develop a method for calcium imaging in spinal cord slices in vitro. This method allowed us to record changes of intracellular free calcium ions concentration (iCa2+ ), that are a major mediator of neuronal plasticity. In this work, we have focused on application of this method in a conventional fluorescence microscope and on the role of different neuromodulators of synaptic activity. Changes of iCa2+ induced by dorsal root electrical stimulation were recorded altogether in 744 dorsal horn (lamina I and II) neurons. In the first series of experiments, stimulation protocols activating preferentially A and A + C dorsal root fibers were used and long-term stability of the calcium responses was verified. The dorsal root stimulation induced in the neurons fast and delayed type of calcium response. Application of AMPA and NMDA receptors antagonists, CNQX (50μM) and MK801 (45μM), reduced the calcium response amplitude and confirmed the importance of glutamate receptors in synaptic activation. In several experiments the effect of capsaicin a TRPV1 receptors agonist, application was tested. Application of even low...

The somatosensory system concerns the sense of touch. It is sectioned into various kinds of touch, such as the proprioceptive sense, providing information of sense of self and position of limbs, and the cutaneous sense, informing of the modalities of touching or being touched. The cutaneous sense is further divided into discriminative touch and affective touch. Discriminative touch is an exteroceptive sense of touch that responds to stimuli of pressure and vibration, and affective touch is an interoceptive sense of touch that corresponds to e.g. pleasant and painful stimuli, communicating information to the brain through A-delta and C-fibers. Recent studies investigates affective touch to have emotional affect on the subjective experience of touch, affecting subjective wellbeing. The aim of this thesis is to examine the sense of touch and its relevant neural correlates, focusing on affective touch and its role in subjective wellbeing and social relations. A presentation of physiological and neural aspects of touch will be held as well as a description of subjective wellbeing. The conclusion for this thesis is that affective touch appears to activate brain areas of orbitofrontal cortex, frontal polar cortice, prefrontal cortex and insula cortex, which are brain areas processing subjective wellbeing, e.g. evaluating positive and negative effect and processing emotional information and behavior. Examining correlations between affective touch and positive affect, negative affect, oxytocin release, social relations and affiliative behavior shows influence from affective touch on subjective wellbeing. A discussion of the current findings is provided, including directions for future research.

The somatosensory system concerns the sense of touch. It is sectioned into various kinds of touch, such as the proprioceptive sense, providing information of sense of self and position of limbs, and the cutaneous sense, informing of the modalities of touching or being touched. The cutaneous sense is further divided into discriminative touch and affective touch. Discriminative touch is an exteroceptive sense of touch that responds to stimuli of pressure and vibration, and affective touch is an interoceptive sense of touch that corresponds to e.g. pleasant and painful stimuli, communicating information to the brain through A-delta and C-fibers. Recent studies investigates affective touch to have emotional affect on the subjective experience of touch, affecting subjective wellbeing. The aim of this thesis is to examine the sense of touch and its relevant neural correlates, focusing on affective touch and its role in subjective wellbeing and social relations. A presentation of physiological and neural aspects of touch will be held as well as a description of subjective wellbeing. The conclusion for this thesis is that affective touch appears to activate brain areas of orbitofrontal cortex, frontal polar cortice, prefrontal cortex and insula cortex, which are brain areas processing subjective wellbeing, e.g. evaluating positive and negative effect and processing emotional information and behavior. Examining correlations between affective touch and positive affect, negative affect, oxytocin release, social relations and affiliative behavior shows influence from affective touch on subjective wellbeing. A discussion of the current findings is provided, including directions for future research.

Orientador: José de Anchieta Castro e Horta Júnior / Resumo: O estado nutricional materno durante períodos críticos de desenvolvimento da prole (fetal e neonatal) é considerado um importante indutor de Programação. No sistema nervoso central, as alterações poderiam ocorrer especialmente em áreas importantes para o controle do comportamento alimentar, como o núcleo do trato solitário (NTS) que se desenvolve durante o período embrionário. A sinalização relacionada à saciedade é mediada pelos aferentes primários glutamatérgicos provenientes do estômago e duodeno, imunorreativos ao transportador vesicular de glutamato – tipo 2 (VGLUT2) e modulada por diversos neuropeptídeos como o hormônio concentrador de melanina (MCH) e o transcrito regulado pela cocaína e anfetamina (CART). Assim, nosso objetivo foi comparar a organização citoarquitetônica e a imunorreatividade ao MCH, ao CART e ao VGLUT2 no NTS de ratos cujas mães foram submetidas à restrição calórica durante a gestação e lactação. Para sua execução, foram realizados acasalamentos de ratos adultos da linhagem Wistar para obtenção das proles, as quais foram objeto de estudo. Após a detecção da prenhez, as fêmeas foram separadas para a formação de dois grupos experimentais: grupo controle (GC), dieta normal ad libitum, e grupo restrição calórica (GR), dieta de 50% de restrição em relação ao grupo controle durante os períodos de gestação e lactação. Os filhotes machos, provenientes dos grupos restrição (GR) e controle (GC), foram divididos em quatro subgrupos etários (n=5) de 21, 28, 50 e... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Maternal nutritional status during critical periods of offspring development (fetal and neonatal) is considered an important Programming inductor. In the central nervous system, alterations could occur especially in areas important for food behavior control, such as the nucleus of the solitary tract (NTS) that develops during the embryonic period. Signs related to satiety are mediated by glutamatergic primary afferents from the stomach and duodenum, immunoreactive to the vesicular glutamate transporter type 2 (VGLUT2) and modulated by various neuropeptides such as melanin concentrating hormone (MCH) and the transcript regulated by cocaine and amphetamine (CART). So, our objective was to compare the cytoarchitectonic organization and immunoreactivity to MCH, CART and VGLUT2 in the NTS of rats whose mothers were subjected to caloric restriction during pregnancy and lactation. For their execution, mating of adult Wistar rats was carried out to obtain proles, which were the object of study. After detection of pregnancy, the females were separated to form two experimental groups: control group (CG), normal ad libitum diet, and caloric restriction group (GR), a 50% restriction diet in relation to the control group during pregnancy and lactation periods. The male offspring from the restriction (GR) and control (CG) groups were divided into four age groups (n = 5) of 21, 28, 50 and 90 days. The number of animals from each offspring, postnatal weight 1, weight and naso-anal length, fo... (Complete abstract click electronic access below) / Mestre

A deeper understanding of both movement control and the effects of nociceptor inputs on our motor systems is critical for proper clinical diagnosis of musculo-skeletal dysfunctions and for development of novel rehabilitation schemes. In the jaw system, masticatory movements are produced by a central pattern generator (CPG) located in the brainstem. Considerable efforts have been made in deciphering this neuronal network. The present thesis contributes towards an increasingly detailed understanding of its essential elements, and presents a hypothesis of how deep somatic pain (i.e. muscle pain) may be evoked and interferes with the masticatory CPG circuitry. In Paper I, the expression of c-Fos-like protein was used as a molecular marker to visualize brainstem neurons that were active during induced fictive mastication in the anesthetized and paralyzed rabbit. Our findings provide a previously lacking detailed record of the neuronal populations that form the masticatory motor pattern. Certain cells were located in brainstem areas previously suggested to be involved in the masticatory CPG. However, it was a new finding that neurons in the dorsal part of the trigeminal main sensory nucleus (NVsnpr-d) may belong to this circuitry. Paper II focused on the discovered neurons in NVsnpr in an in vitro slice preparation from young rats.  Intracellular recordings allowed us to define two cell types based on their response to depolarizing current. Microstimulation applied to the trigeminal motor nucleus, its reticular border, the parvocellular reticular formation and the nucleus reticularis pontis caudalis, elicited postsynaptic potentials in 81% of the neurons tested. Responses obtained were predominately excitatory and sensitive to gluta-matergic antagonists DNQX or/and APV. Some inhibitory and biphasic responses were also evoked. Bicuculline methiodide or strychnine blocked the IPSPs indicating that they were mediated by GABAA or glycinergic receptors. About one third of the stimulations activated both types of neurons antidromically. Neurons in NVsnpr-d seem to gather all the conditions that can theoretically account for a role in masticatory rhythm generation. In Paper III, the masticatory model system was used to investigate the possible role of muscle spindle primary afferents in development of persistent musculoskeletal pain. Following intramuscular acidic (pH 4.0) saline injections of rat masseter muscles, in vitro whole cell recordings were done from jaw closing muscle spindle somata located in the trigeminal mesencephalic nucleus (NVmes). Compared to control neurons, the somata of afferents exposed to acid had more hyperpolarized membrane potentials, more hyperpolarized thresholds for firing, high frequency membrane oscillations and ectopic bursting of action potentials. These changes in membrane properties lasted for up to 35 days. Within the same time frame experi-mental animals showed hypersensitivity to touch on the skin covering the injected muscle. Similar saline injections also resulted in a significant increase of activity dependent c-Fos expression in NVmes neurons compared to controls. Immuno-fluorescence and lectin binding studies indicated that small-caliber muscle afferents containing known nociceptor markers (CGRP, SP, P2X3, TRPV1 and IB4) and expressing glutamate receptors are found close to the annulo-spiral endings of the NVmes afferents. Combined, our new observations support the hypothesis that excessive release of glutamate, within muscle spindles due to ectopically evoked antidromic action potentials, could lead to development of persistent musculoskeletal pain by activation and/ or sensitization of adjacent muscle afferent nociceptors.

During dexterous manipulation with the fingertips, forces are applied to objects' surfaces. To achieve grasp stability, these forces must be appropriate given the properties of the objects and the skin of the fingertips, and the nature of the task. It has been demonstrated that tactile sensors in the fingertips provide crucial information about both object properties and mechanical events critical for the control of fingertip forces, while in certain tasks vision may also contribute to predictions of required fingertip actions. This thesis focuses on two specific aspects of the sensory control of manipulation: (i) how individual fingers are controlled for grasp stability when people restrain objects subjected to unpredictable forces tangential to the grasped surfaces, and (ii) how tactile sensors in the fingertips encode direction of fingertip forces and shape of surfaces contacted by the fingertips. When restraining objects with two fingers, subjects adjust the fingertip forces to the local friction at each digit-object interface for grasp stability. This is accomplished primarily by partitioning the tangential force between the digits in a way that reflects the local friction whereas the normal forces at the involved digits are scaled by the average friction and the total load. The neural control mechanisms in this task rely on tactile information pertaining to both the friction at each digit-object interface and the development of tangential load. Moreover, these mechanisms controlled the force application at individual digits while at the same time integrating sensory inputs from all digits involved in the task. Microneurographical recordings in awake humans shows that most SA-I, SA-II and FA-I sensors in the distal phalanx are excited when forces similar to those observed during actual manipulation are applied to the fingertip. Moreover, the direction of the fingertip force influences the impulse rates in most afferents and their responses are broadly tuned to a preferred direction. The preferred direction varies among the afferents and, accordingly, ensembles of afferents can encode the direction of fingertip forces. The local curvature of the object in contact with the fingertip also influenced the impulse rates in most afferents, providing a curvature contrast signals within the afferent populations. Marked interactions were observed in the afferents' responses to object curvature and force direction. Similar findings were obtained for the onset latency in individual afferents. Accordingly, for ensembles of afferents, the order by which individual afferents initially discharge to fingertip events effectively represents parameters of fingertip stimulation. This neural code probably represents the fastest possible code for transmission of parameters of fingertip stimuli to the CNS.

Background: Interpersonal touch is an irreplaceable contributor to our daily social life. It is a powerful tool for communicating emotions and, at this, enables the formation and maintenance of relationships. Affective touch is one of the first interactions in parent-child-dyads and contributes positively to the cognitive and social development of children and adolescents. In recent years, a group of nerve fibres was detected and identified as a key player in the perception of affective touch. These so-called C-tactile afferents are specialized in the perception of human-to-human caress-like touch. They are optimally activated/stimulated by light and slowly stroking touch at velocities between 1 and 10 cm/s (Löken et al., 2009). Interestingly, in a standardized experiment, these tactile stimulations are likewise hedonically rated and perceived as most pleasant. C-tactile afferents project to the insular as well as somatosensory cortex at a slow speed of around 1 m/s. The insular cortex is suggested to be involved in emotional processing and integration of sensory impressions, above else. Against this background, C-tactile afferents are characterized as key players in affective touch perception and mark an antipole to discriminative touch perception and Aβ-fibres. Affective touch contributes to the cognitive and social development in children (Field, 2010) and C-tactile mediated affective touch perception is altered in individuals with Autism Spectrum Disorder (Kaiser et al., 2016). First evidence further suggests a contribution of C-tactile afferents in the perception of erotic touch (Jönsson et al., 2015). Against this background of evidence for the role of C-tactile afferents, the social-touch-hypothesis was formed (Olausson et al., 2010), stating a contribution of C-tactile afferents in the formation and maintenance of interpersonal relationships. Still, only few approaches thus far have investigated the actual influence of C-tactile mediated affective touch perception on interpersonal behaviour. Individuals seem to differ in their peripheral and central characteristics and processing of affective touch, but a method to quantify these differences is still missing. Aim: In the presented articles, we first investigated the relationship between C-tactile mediated touch perception and sexual desire and behaviour (paper 1). Next, a procedure to test the individual preference of affective touch was developed and examined (paper 2). Recent research described C-low-threshold mechanoreceptors – the equivalent of C-tactile afferents in rodents - to be arranged around certain hair follicles (Li et al., 2011). We thus hypothesized in paper 3, that hair follicle density might be related to the density of C-tactile afferents and that affective touch perception might be predicted by hair follicle density. The article describes and examines a method for quantification of C-tactile afferents in humans. Materials and Methods: Papers 1 and 3 present the results of a psychophysical study conducted on a sample of relatively young and subjectively healthy participants at the Medical Faculty of Dresden University of Technology. In paper 3, the study is compared and analysed in relation to another study as part of a cooperation together with the University of Gothenburg (Sweden). The study design involved the standardized application of different CT-optimal as well as –suboptimal stroking stimuli on the forearm using a computer-assisted robotic device (Rotary Tactile Stimulator). The participants were asked to rate these tactile stimuli concerning different hedonic qualities (pleasantness and eroticism) on visual analogue scales. Sexual Desire and sexual behaviour were determined indirectly through questionnaires. The study design further included the Cyanoacrylate Skin Stripping Method that enables sampling of the upper layer of the skin – the stratum corneum. These samples were analysed light-microscopically in order to determine the hair follicle density of the participants. Paper 2 reviews a different study which was conducted at the Center for Social and Affective Neurosciences at the University of Linköping (Sweden). In this study, the Test of Preferred-Velocity was examined and validated as a measure of individually preferred touch stimuli on a sample of young and healthy participants. Analogous to the study design described in paper 1 and 3, tactile stimuli were applied using the Rotary Tactile Stimulator as well. The Test of Preferred-Velocity includes a forced choice paradigm in which the preferred stimulus out of different pairs needs to be reported. The paper describes two different set-ups applying the test: First, the Test of Preferred Velocity was validated and tested for retest-reliability. Afterwards, a short version of the test was applied on both the forearm and the palm of the hand, where it was each validated and compared in-between. The following measures were determined in order to analyse and describe the individual sensitivity for C-tactile mediated affective touch perception: In paper 1, the erotic touch differentiation was determined as the difference of eroticism ratings between C-tactile optimal (1 cm/s) and C-tactile suboptimal (30 cm/s) tactile stimuli. Pleasant touch awareness equally reflects the sensitivity for pleasant touch in paper 3. However, this measure further considers the average level of hedonic ratings. Results: C-tactile optimal stroking stimuli at velocities between 1 and 10 cm/s were perceived as both pleasant and erotic. This confirms the results of a previous study by Jönsson et al. (2015), where a contribution of C-tactile afferents to erotic touch perception was suggested. According to the presented hypotheses, a gender-specific relation between C-tactile mediated erotic touch perception and sexual desire as well as sexual behaviour could be detected (paper 1): Within the group of female participants, erotic touch differentiation was positively correlated with the desire for sexual interaction with a partner. In the male sub-group of participants however, erotic touch differentiation was negatively related to the actual frequency of sexual interactions with a partner in the course of the last month. The Test of Preferred-Velocity was reviewed as a reliable procedure for determining the individually preferred stroking velocity of C-tactile-targeted touch, presented a high test-retest-reliability and was validated with the hedonic ratings of the participants (paper 2). The short version of the test presented equally reliable features and was related with the hedonic ratings when tested on the forearm but not the palm of the participants. Hair follicle density, however, could not be confirmed as a method to quantify C-tactile mediated affective touch perception or fibre density (paper 3). In the described extended sample of paper 3, the previously suggested and well-known rating patterns of C-tactile mediated affective touch perception were confirmed. Interestingly, a gender-specific difference in the hedonic evaluation of touch could be determined when female participants consistently rated the applied stimuli as significantly more pleasant and erotic than men. Conclusions: The presented articles confirm and extend previous assumptions on the properties and function of C-tactile afferents in humans. At this, C-tactile afferents seem to contribute significantly to the complex concepts of pleasant and erotic touch perception and have an impact on interpersonal behaviour. The results give insights into how gender might modulate C-tactile-mediated touch perception and did not find support for the hypothesis that hair follicle density and C-tactile sensitivity might be related. The Test of Preferred-Velocity however, might be used as a tool to investigate the individually preferred stroking stimulus in further studies.:Abbreviations 1 Figure legend 1 Introduction 2 INTRODUCTION TO THE SOMATOSENSORY SYSTEM: DISCRIMINATIVE AND AFFECTIVE TOUCH 2 C-TACTILE AFFERENTS – PERIPHERAL CHARACTERISTICS OF AFFECTIVE TOUCH 3 SPINAL AND CORTICAL PROCESSING OF C-TACTILE STIMULATION 5 THE “SOCIAL TOUCH HYPOTHESIS” 6 C-TACTILE MEDIATED EROTIC TOUCH PERCEPTION 7 INDIVIDUAL LEVELS OF C-TACTILE SENSITIVITY 9 HAIR FOLLICLE DENSITY AND NERVE FIBER DISTRIBUTION 11 Discussion 14 C-TACTILE AFFERENTS AND EROTIC TOUCH PERCEPTION 14 GENDER DIFFERENCES OF AFFECTIVE TOUCH PERCEPTION 15 STABILITY AND QUANTIFICATION OF AFFECTIVE TOUCH PERCEPTION: INDIVIDUAL PATTERNS OF AFFECTIVE TOUCH AND HAIR FOLLICLE DENSITY 16 LIMITATIONS 19 CONCLUSIONS 21 Zusammenfassung 22 Summary 26 References 29 Publication data 34 Annex I: C-Tactile Mediated Erotic Touch Perception Relates to Sexual Desire and Performance in a Gender-Specific Way. Annex II: The individual preferred velocity of stroking touch as a stable measurement. Annex III: The relation between human hair follicle density and touch perception. / Hintergrund: Zwischenmenschliche Berührung ist ein wichtiger Bestandteil unseres täglichen sozialen Lebens. Sie trägt wesentlich zur Entstehung und Aufrechterhaltung von Beziehungen bei und kann ein sehr kraftvolles, emotionales Kommunikationsmittel sein. In der Interaktion zwischen Eltern und Kind wirkt sich affektive Berührung positiv auf die kognitive und soziale Entwicklung der Heranwachsenden aus und ist im Allgemeinen unter anderem mit einem gesunden Körperbewusstsein und Interozeption verbunden. In den 1990er Jahren konnte eine Gruppe unmyelinisierter Nervenfasern in der behaarten Haut des Menschen identifiziert werden, welche auf die Wahrnehmung solch zwischenmenschlicher, affektiver Berührung spezialisiert sind. Diese sogenannten C-taktilen Nervenfasern werden von langsam streichelnden Berührungen (Geschwindigkeit 1 – 10 cm/s) mit nur leichtem Druck – ähnlich dem sanften Streicheln durch eine menschliche Hand - optimal aktiviert (Löken et al., 2009). Interessanterweise wird diese Stimulierung gleichermaßen in Experimenten als besonders angenehm beschrieben und empfunden. Die Stimuli werden von C-taktilen Nervenfasern mit einer langsamen Leitgeschwindigkeit (ca. 1 m/s) an den somatosensorischen Kortex, aber auch an die Inselrinde des Gehirns weitergeleitet. Letztere trägt unter anderem zu emotionaler Verarbeitung und Integration von Sinneseindrücken bei. Mit diesen Eigenschaften stellen die C-taktilen Nervenfasern einen funktionellen Gegenpol zu den Hauptakteuren der diskriminativen Berührungsempfindung, den Aβ-Fasern, dar. Affektive Berührungswahrnehmung wirkt sich positiv auf die kognitive und soziale Entwicklung von Kindern aus (Field, 2010) und C-taktil vermittelte Berührungswahrnehmung wird in Individuen mit Autismus verändert verarbeitet (Kaiser et al., 2016). Erste Ergebnisse deuten darauf hin, dass C-taktile Nervenfasern weiterhin an der Wahrnehmung erotischer Berührungen beteiligt sind (Jönsson et al., 2015). Vor diesem Hintergrund wird diese Form der taktilen Interaktion auch als „soziale Berührung“ beschrieben, die für die Formung und Aufrechterhaltung zwischenmenschlicher Beziehungen eine wesentliche Bedeutung hat (Olausson et al., 2010). Dabei haben nur wenige Studien bisher die tatsächliche Auswirkung C-taktil vermittelter affektiver Berührungswahrnehmung auf das zwischenmenschliche Verhalten untersucht. Individuen scheinen sich hinsichtlich ihrer peripheren oder zentralen Charakteristika der affektiven Berührungswahrnehmung zu unterscheiden – eine Methode zur Quantifizierung dieser Charakteristika wurde jedoch bisher noch nicht entwickelt. Fragestellung: In den hier vorgestellten Arbeiten wurde zunächst die Beziehung zwischen C-taktil vermittelter Berührungswahrnehmung und sexuellem Verhalten und Verlangen untersucht (Paper 1). In einer zweiten Veröffentlichung wird ein Testverfahren zur Bestimmung der individuell bevorzugten affektiven Berührung vorgestellt. Studien an Nagetieren haben ergeben, dass die den C-taktilen Nervenfasern entsprechenden Mechanorezeptoren um bestimmte Haarfollikel herum angefunden werden (Li et al., 2011). Daraus resultierte die Fragestellung aus Paper 3, einen Zusammenhang zwischen der Haarfollikeldichte am Unterarm und der C-taktil vermittelten Berührungswahrnehmung zu untersuchen. In der Arbeit wird auf dieser Grundlage eine Methode zur Quantifizierung C-taktiler Nervenfasern getestet. Material und Methoden: Paper 1 und 3 präsentieren die Ergebnisse einer psychophysischen Studie an jungen und subjektiv gesunden Probanden, welche an der Medizinischen Fakultät der TU Dresden durchgeführt wurde. In Paper 3 wird diese Studie im Rahmen einer Kooperation mit der Universität Göteborg mit einer dort durchgeführten ähnlichen Studie verglichen und ausgewertet. Die Teilnehmer dieser Studie haben mithilfe eines computer-assistierten Roboters standardisierte dynamische Berührungen mit sowohl C-taktil optimalen als auch suboptimalen Stimuli am Unterarm erhalten. Diese Berührungen wurden hinsichtlich verschiedener hedonischer Aspekte (Angenehmheit, Erotizität) anhand von Visuellen Analog-Skalen bewertet. Sexuelles Verhalten und sexuelles Verlangen wurden mithilfe von Fragebögen ermittelt. Mithilfe der Cyanoacrylate Skin Stripping Methode wurde den Probanden außerdem eine Probe des Stratum corneum der Unterarmhaut entnommen. Anhand dieser Proben wurde lichtmikroskopisch die Haarfollikeldichte pro cm² bestimmt. Die Ergebnisse einer weiteren Studie, welche an der Universität Linköping (Schweden) durchgeführt wurde, werden in Paper 2 aufgearbeitet. In dieser Studie wurde an einer Kohorte von jungen und gesunden Probanden ein Testverfahren (Test of Preferred Velocity) entwickelt und validiert, mithilfe dessen die individuell bevorzugten Berührungs-Stimuli bestimmt werden können. Der Test of Preferred Velocity verwendet ebenso den computer-assistierten Roboter Rotary Tactile Stimulator, mithilfe dessen in einem Forced Choice Paradigma verschiedene Berührungs-Stimuli vergleichend angeboten wurden. Die Studie beinhaltet zwei Teile: Zunächst werden Validierung und Test-Retest-Reliabilität des Testverfahrens beschrieben. Eine Kurzform der Methode wird im zweiten Teil vergleichend an der Handfläche und dem Unterarm von einer neuen Kohorte getestet und validiert. Verschiedene Werte werden für die Einschätzung der individuellen Sensitivität für C-taktil vermittelte affektive Berührung herangezogen: In Paper 1 wird die sogenannte erotic touch differentiation als Differenz zwischen den Erotizitäts-Bewertungen von C-taktil optimalen (1 cm/s) und C-taktil suboptimalen (30 cm/s) Berührungs-Stimuli ermittelt. Die pleasant touch awareness spiegelt einen ähnlichen Wert für die Sensitivität angenehmer Berührungen in Paper 3 wieder, wobei dieser zur durchschnittlichen Höhe der jeweiligen hedonischen Bewertung in Bezug gesetzt wird. Ergebnisse: In der hier vorgestellten Arbeit zeigt sich, dass C-taktil optimale Berührungs-Stimuli mit einer Geschwindigkeit zwischen 1 und 10 cm/s gleichermaßen als angenehm und erotisch empfunden werden. Dies bestätigt die Ergebnisse einer früheren Studie, welche bereits eine Beteiligung C-taktiler Nervenfasern an der Wahrnehmung erotischer Berührungen feststellen konnten (Jönsson et al., 2015). Entsprechend der vorgestellten Hypothesen konnte ein geschlechtsspezifischer Zusammenhang zwischen Werten C-taktil vermittelter erotischer Berührungswahrnehmung und sexuellem Verlangen und Verhalten beschrieben werden (Paper 1): Während unter den Probandinnen ein signifikanter Zusammenhang zwischen der erotic touch differentiation und dem Verlangen nach einer sexuellen Interaktion zu verzeichnen war, konnte in der Gruppe der männlichen Studienteilnehmer ein negativer Zusammenhang zwischen der erotic touch differentiation und der Anzahl tatsächlich stattgefundener sexueller Interaktionen im letzten Monat beobachtet werden. Der Test of Preferred Velocity zeigte sich als geeignet, um individuell bevorzugte Berührungs-Stimuli zu bestimmen und bewies eine hohe Test-Retest-Reliabilität (Paper 2). Mithilfe der hedonischen Bewertung der verwendeten Stimuli konnte der Test weiterhin validiert werden. Die Kurzversion des Testes zeigt ähnlich zuverlässige Eigenschaften und steht bei der Anwendung am Unterarm, nicht jedoch auf der Leistenhaut der Handfläche, mit den hedonischen Bewertungen in Zusammenhang. Die Haarfollikeldichte als Möglichkeit der Quantifizierung C-taktil vermittelter Berührung ließ sich nicht bestätigen (Paper 3). Anhand einer großen Stichprobe können allerdings die bisher bekannten Bewertungsmuster C-taktil vermittelter Berührungen erneut bestätigt werden. Auch hier wird ein geschlechtsspezifischer Unterschied in der hedonischen Bewertung zugunsten der Studienteilnehmerinnen beschrieben. Schlussfolgerungen: Die vorgestellten Arbeiten bestätigen und erweitern bisherige Erkenntnisse zu Eigenschaften und Funktion C-taktiler Nervenfasern im Menschen. C-taktile Nervenfasern scheinen signifikant zu dem komplexen Konzept der Wahrnehmung angenehmer und erotischer Berührungen beizutragen und sich auf das zwischenmenschliche Verhalten auszuwirken. Erstmals werden in diesen Arbeiten auch geschlechtsspezifische Eigenschaften affektiver Berührungswahrnehmung näher. Der vermutete Zusammenhang zwischen Haarfollikeldichte und affektiver Berührungswahrnehmung ließ sich nicht bestätigen. Der Test of Preferred Velocity kann jedoch zur individuellen Quantifizierung der bevorzugten Berührungs-Stimuli in weiteren Studien verwendet und ggf. weiterentwickelt werden.:Abbreviations 1 Figure legend 1 Introduction 2 INTRODUCTION TO THE SOMATOSENSORY SYSTEM: DISCRIMINATIVE AND AFFECTIVE TOUCH 2 C-TACTILE AFFERENTS – PERIPHERAL CHARACTERISTICS OF AFFECTIVE TOUCH 3 SPINAL AND CORTICAL PROCESSING OF C-TACTILE STIMULATION 5 THE “SOCIAL TOUCH HYPOTHESIS” 6 C-TACTILE MEDIATED EROTIC TOUCH PERCEPTION 7 INDIVIDUAL LEVELS OF C-TACTILE SENSITIVITY 9 HAIR FOLLICLE DENSITY AND NERVE FIBER DISTRIBUTION 11 Discussion 14 C-TACTILE AFFERENTS AND EROTIC TOUCH PERCEPTION 14 GENDER DIFFERENCES OF AFFECTIVE TOUCH PERCEPTION 15 STABILITY AND QUANTIFICATION OF AFFECTIVE TOUCH PERCEPTION: INDIVIDUAL PATTERNS OF AFFECTIVE TOUCH AND HAIR FOLLICLE DENSITY 16 LIMITATIONS 19 CONCLUSIONS 21 Zusammenfassung 22 Summary 26 References 29 Publication data 34 Annex I: C-Tactile Mediated Erotic Touch Perception Relates to Sexual Desire and Performance in a Gender-Specific Way. Annex II: The individual preferred velocity of stroking touch as a stable measurement. Annex III: The relation between human hair follicle density and touch perception.

No description available.