Cannabinoid receptors (CBR) are the most abundant G-protein coupled receptors in the mammalian brain with the highest densities within the cerebellum (Herkenham et al., 1990). Cannabinoid manipulations have been reported to cause deficits in cerebellar-dependent learning (Kishimoto and Kano, 2006; Skosnik et al., 2007; Steinmetz and Freeman, 2010; 2013). Cannabinoid receptors-1 (CB1R) have been hypothesized to be important in the establishment of long-term depression within the cerebellar cortex (Levenes et al., 1998; Safo and Regehr, 2005). However, all investigations in vivo have used global manipulations and have not attempted to localize or characterize these receptors during cerebellar-dependent learning. Chapter 2 systematically examined localization within the cerebellar cortex of cannabinoid effects on eyeblink conditioning, a type of cerebellum-dependent learning. Local infusions into a specific portion of the cerebellar cortex, the eyeblink conditioning microzone, resulted in deficits in learning similar to systemic injections. Additionally, infusions of cannabinoids into the eyeblink conditioning microzone, and no other parts of the cerebellar cortex or deep nuclei, were responsible for the deficits. Finally, tetrode recordings were made in Purkinje cells while receiving either CBR agonist or vehicle injections prior to training. Fewer Purkinje cells exhibited learning-related decreases in activity when the rat was administered a CBR agonist as compared to when it was injected with the vehicle. The CBR administered Purkinje cells also showed earlier onsets and smaller amplitudes in their learning-related activity. Purkinje cells that show a learning-related increase in activity were not affected by cannabinoid administration. The impairment in Purkinje cell plasticity was not observed after the rats reached asymptotic levels of learning. These results indicate that CBR agonist administration disrupts the induction of plasticity within the cerebellar cortex and this may account for the behavioral deficit in eyeblink conditioning. Chapter 3 examined whether infusions of the CBR agonist into the cerebellar cortex impaired forebrain-dependent learning as well as forebrain-independent associative learning. Similar to subcutaneous injections, forebrain-dependent trace eyeblink conditioning was unimpaired, whereas forebrain independent delay eyeblink conditioning was impaired. These findings provide evidence that plasticity mechanisms that are modulated by cannabinoids do not play a significant role in trace eyeblink conditioning. Finally, in Chapter 4 the role of CBRs and endocannabinoids during memory consolidation were examined. CBR and endocannabinoid manipulations prior to training resulted in impaired eyeblink conditioning. However, a CBR agonist or a drug increasing endocannabinoid levels resulted in enhanced consolidation when administered 1 hour post-training. In contrast, a CBR antagonist or an endocannabinoid decreasing drug resulted in impairments 1 hour post-training. Thus, CBRs and endocannabinoids appear to be important in learning and consolidation of cerebellar-dependent learning.

Although Rembrandt van Rijn owned over eighty pieces of sculpture, studies regarding his use of the collection are in short supply and tend to be either formal, tracing the few images of sculpture in Rembrandt's oeuvre to those listed in his 1656 bankruptcy inventory, or else they refer to his use of classical sculpture in general terms as an inspiration for his history paintings. This study shifts emphasis from formal and iconographic issues to Rembrandt's studio practices and working methods. It examines his manipulation of the border between reality and illusion (what Ovid termed "the art that conceals art"): his effort to "incarnate" his sculptural sources by wrapping them in textiles and giving them the appearance of flesh. Seventeenth-century theory provides the foundation for this hypothesis: artists/theorists such as Karl van Mander, Peter Paul Rubens, and Philips Angel promoted the judicious use of sculpture and encouraged artists to transform its marmoreal surface into pliant flesh; Van Mander advised painters to make the thin garments of classical statues more appropriate for Northern paintings by wrapping them in woolen cloth; he also encouraged artists to "steal arms, legs, hands, and feet" from works of art and synthesize them into new creations. Esteemed precedents also support the hypothesis: recent studies of Cornelis Cornelius van Haarlem, Hendrick Goltzius, and Bartholomeus Spranger examined their use of Renaissance bronzes, an inexpensive and plentiful source that Rembrandt also seems to have tapped. Paragone, a popular debate in both Amsterdam and Leiden, is another facet of this study. Empirical observations reveal patterns in Rembrandt's use of sculpture: several etchings of his studio show busts adorned with hats or wrapped in fabric (a practice also described in a seventeenth-century poem about Rembrandt); a number of his head studies, genre, and history paintings suggest that he used busts of Roman emperors for models. The less subtle artistry of his students and his colleague Jan Lievens also exposes their use of clothed statues and thereby corroborates the hypothesis that Rembrandt's reliance on sculpture for models was more prevalent and artful (in the sense of covert) than has previously been noted. / Art History

Ratten verwenden Schnurrhaare (Vibrissen) zur Berührungswahrnehmung, und die Leitungsbahn von den Vibrissen zum primären somatosensorischen Areal (Barrel Cortex, BC) ist gut untersucht. Ratten zeigen auch vielfältiges Sozialverhalten, u.a. Berührung von Artgenossen mit ihren Vibrissen. Es ist jedoch unbekannt, wie diese sozialen Berührungssignale im Gehirn repräsentiert sind. Deshalb hatte die vorliegende Studie zum Ziel, die neuronale Repräsentation von sozialen Berührungen im BC zu untersuchen und mit anderer somatosensorischer Stimulation zu vergleichen. Mit extrazellulären Einzelzellableitungen in sich frei bewegenden Ratten habe ich gezeigt, dass die Aktivität eines Großteils von Neuronen im BC durch soziale Berührungen moduliert wird. Antworten waren meist erregend und Feuerraten während sozialer Interaktionen unterschieden sich zwischen kortikalen Schichten. Ratten bevorzugten Interaktionen mit Artgenossen gegenüber unbelebten Stimuli. Auch die Berührungsstrategien unterschieden sich, dabei wurden Objekte mit regelmäßigeren Bewegungen abgetastet, und die Vibrissen weiter vorgestreckt. Neuronale Antworten unterschieden sich ebenso, mit leicht aber konsistent schwächeren Antworten auf Objekte. Interessanterweise habe ich geschlechtsspezifische Unterschiede in neuronalen Antworten beobachtet. Der ausgeprägteste war die stärkere Modulation regulär-feuernder (RF) Zellen in Männchen während sozialer Berührungen. Dieser Unterschied konnte nicht mit sozialem Berührungsverhalten erklärt werden, was eventuell auf eine neurale Grundlage dieser Differenz hindeutet. Zudem feuerten RF-Zellen von Weibchen deutlich seltener, wenn das Weibchen im Östrus war. Zusammenfassend ist dies die erste Studie, die soziale Signale in einem primären sensorischen Areal bei sich frei bewegenden Tieren auf zellulärer Ebene untersuchte. Sie legt nahe, dass die Repräsentationen sensorischer Hirnrinde weniger stimulusabhängig und stärker top-down-moduliert sein könnten, als zuvor angenommen. / Rats use their stiff facial hairs (whiskers) for somatosensation, and the pathway from the whiskers to the primary somatosensory cortex (barrel cortex, BC) is well known. Rats also show diverse social behaviors, including touch of conspecifics with their whiskers. The representation of these social touch signals in the brain is however unknown. Thus, the present study aimed at characterizing the neuronal representation of social touch signals in BC and comparing them with non-social somatosensory stimulation. Using extracellular single-cell recordings in freely-moving rats, I could show that the activity of a large fraction of BC neurons is modulated by social touch. Responses were typically excitatory and the pattern of firing rates during interactions differed between cortical layers. Rats preferred interactions with alive conspecifics over inanimate stimuli. Whisking strategies also differed in that inanimate stimuli were whisked at with more regular movements from more protracted set angles. Neuronal responses were also different, such that objects elicited slightly but consistently weaker responses than alive rats. Interestingly, I observed sex-specific differences in neuronal responses. Prominently, there was stronger modulation by social touch in regular-spikers (RS) recorded from males. This could not be explained by behavioral measures, possibly indicating a neural origin of this difference. Further, RS from females fired much more weakly when females were in estrus. In summary, this is the first study that investigated social signals in a primary sensory area of freely-moving animals at the cellular level. It suggests that representations in sensory cortices might be less stimulus-driven and more top-down modulated than previously thought.

Title: Effect of surface electrode type on quality of decomposition of surface EMG signal Objectives: The aim of this thesis is to evaluate the effect of surface electrode type, which was used for EMG record, on the quality of decomposition of surface EMG signal using decomposition software EMGlab. Methods: The form of the thesis is an experimental essay. It was detected an EMG signal from one healthy volunteer during mild cyclic contraction. It was used three different types of electrodes (standard surface electrode, tetrode, tetrode with saw-off spikes) for EMG signal detection. These signals were decomposed in program EMGlab. The results were processed in program MS Excel, compared with each other and graphically displayed. Results: The measurement verified a hypothesis which claimed that the used type of electrode affects the quality of automatic decomposition. The best results of automatic decomposition provide the signal gained from the standard surface electrode. Key words: action potential, decomposition, surface electrodes, EMG signal, tetrode, electromyography

While signatures of attention can be observed in widespread areas within and outside of cortex, the control of attention is thought to be regulated by higher cognitive brain areas, such as the prefrontal cortex. In their recent study on mice Kim et al. could show that successful allocation of attention is characterized by increased spiking of a specific type of inhibitory interneurons, the parvalbumin neurons, and higher oscillatory activity in the gamma band in the local prefrontal network. It was recently demonstrated that encoding of working memory in prefrontal areas is linked to bursts of gamma oscillations, a discontinuous network process characterized by short periods of intense power in the gamma band. The relationship between attention and working memory is unclear, and it is possible that these two cognitive processes share encoding principles. To address this gap, the electrophysiological data collected in the Carlén Lab have been analyzed with advanced spatio-temporal approaches. In particular, we have analyzed bursting gamma activity in medial prefrontal cortex during attentional processing and investigated the similarities to gamma bursting observed during working memory. Gamma-band bursts during attention were reliably detected with several methods. We have characterized several features of the bursts, including the occurrence, duration and amplitude. The neuronal firing rates during and outside of bursts have also been computed. We investigated the correlation between different criteria characterizing the gamma burst and successful vs failed allocation of attention. Control data were generated to discuss the obtained results. The aim of the study was to explore the hypothesis that the medial prefrontal cortex encodes attention trough gamma bursts, which could reveal some similarities and differences in coding of central cognitive processes. No clear difference was found in the characterization between successful and failed allocation of attention. In addition, results were very similar in control set and original data. No underlying mechanism could be identified from this analysis. Therefore, as the bursts occurring in the gamma band in the prefrontal cortex (PFC) were not discriminative with respect to the different tested conditions, they do not seem to encode information related to attention. / Även fast flera olika hjärnområdens aktivitet kan korreleras med uppmärksamhet, anses kontrollen av uppmärksamhet regleras av högre kognitiva hjärnområden, såsom främre hjärnbarken. I en nyligen publicerad artikel studerade Kim et al. hjärnaktiviteten hos möss och kunde visa att en framgångsrik uppmärksamhet kännetecknas av en ökad aktivitet av en specifik typ av inhiberande nervceller, parvalbumin celler, och högre oscillerande aktivitet i gammafrekvens i främre hjärnbarkens lokala nätverk. Det har nyligen visats att kodning av arbetsminne i främre hjärnbarken är kopplat till utbrott av gamma-oscillationer, en diskontinuerlig nätverksprocess som kännetecknas av korta perioder av intensiva oscillationer av det lokala nätverket i gammafrekvens . Relationen mellan uppmärksamhet och arbetsminne är oklar, och det är möjligt att dessa två kognitiva processer delar kodningsprinciper. För att minska detta gap av kunskap har den elektrofysiologiska datan som samlats in i Carlén Lab analyserats med avancerade spatio-temporala tillvägagångssätt. I synnerhet har vi analyserat utbrott i gammaaktivitet i främre hjärnbarken under uppmärksamhet och undersökt likheterna med gamma- utbrott observerade under arbetsminne. Gamma-bandutbrott under uppmärksamhet påvisades på ett tillförlitligt sätt med flera metoder. Vi har karaktäriserat flera funktioner hos utbrotten, inklusive förekomsten, varaktigheten och amplituden. De enskilda cellernas aktivitet undersöktes även under och utanför utprotten av gamma-oscillationer. Vi undersökte sambandet mellan de olika kriterier som karakteriserar gamma-utbrott under framgångsrik mot misslyckad allokering av uppmärksamhet. Kontrolldata genererades för att diskutera de erhållna resultaten. Syftet med studien var att utforska hypotesen att den främre hjärnbarken kodar uppmärksamhet genom gamma-utbrott, vilket kan avslöja vissa likheter och skillnader i kodning av centrala kognitiva processer. Ingen klar skillnad hittades i karaktäriseringen mellan framgångsrik och misslyckad allokering av uppmärksamhet. Dessutom var resultaten mycket likartade i kontrolluppsättningen och den ursprungliga datan. Ingen underliggande mekanism kunde identifieras ur denna analys. Eftersom de utbrott som uppstod i gamma-bandet i främre hjärnbarken inte var unika med hänsyn till de olika testade förhållandena, tycks de därför inte koda information relaterad till uppmärksamhet.

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