Consolidation of associative memories may depend on communication between the lateral entorhinal cortex (LEC) and hippocampus (HPC) for recently learned memories and the LEC and medial prefrontal cortex (mPFC) for remote memories. To determine whether direct connections between these regions are necessary for the retrieval of a recently or remotely learned memory, rats acquired an associative memory through trace eyeblink conditioning and were tested for memory retention after inactivating the regions of interest with the GABAA agonist, muscimol. Inactivating the LEC-HPC connection did not impair memory retrieval. However, inactivating the LEC-mPFC connection impaired remote, but not recent, memory retrieval. Thus, the LEC and mPFC connection is necessary for the retrieval of a remotely, but not recently learned associative memory. Increased reliance on the entorhinal-prefrontal connection indicates the strengthening of functional connectivity between the two regions, which may be a biological correlate for the proposed reorganization during systems consolidation.

Male rat copulatory behavior is dependent on Testosterone (T) and its metabolites, estradiol (E2) and dihydrotestosterone (DHT). The estrogen receptor (ER) isoforms, ERα and ERβ, exist in the medial Amygdala (MEA) and either receptor might mediate mating behavior. Therefore, the effects of selective estrogenic MEA implants: propyl pyrazole triol (PPT, ERα agonist), diarylpropionitrile (DPN, ERβ agonist), and 1-methyl-4-phenyl pyridinium (MPP, ERα antagonist) were compared to E2 in maintaining sexual behavior. Four groups of male rats were castrated and administered DHT s.c. and bilateral MEA implants containing either cholesterol, E2, PPT or DPN. An additional group of gonadally intact male rats received bilateral MPP-MEA implants. The post-surgical trials showed a significant decrease in the mating behavior of groups that received cholesterol, PPT, or DPN-MEA implants. However, sexual behavior was maintained in male rats that received the E2 or MPP-MEA implants. These results suggest a differential response of the MEA to E2.

Els coneixements actuals sobre els efectes crònics de l'alcohol en el SNC són encara força limitats. Malgrat haver identificat en part els canvis que subjauen a fenòmens com la tolerància o la dependència, el mecanisme responsable de l'addicció encara és desconegut. Diversos estudis s'han centrat en la neurotransmissió GABAèrgica, glutamatèrgica, dopaminèrgica i serotoninèrgica, aquests sistemes quan son afectats crònicament per l'alcohol, responen amb adaptacions que o bé són reversibles, o es compensen i neutralitzen després d'un període d'abstinència, no poden per tan ésser el suport d'un fenomen permanent com l'addicció. Estudis fets en animals consumidors voluntaris de dosis tòxiques d'alcohol, han mostrat diferències significatives respecte als controls en diversos processos d'aprenentatge tant excitatori com inhibitori, i han estat identificants canvis tan fisiològics com moleculars en la transmissió colinèrgica de tipus nicotínic. Aquests canvis, sensibilització i regulació a l'alça del receptor nicotínic, són presumiblement irreversibles, no obstant, desconeixem si els processos d'aprenentatge, i els substrats neurals subjacents, es troben alterats en aquests animals alcohòlics durant l'abstinència. En aquesta tesi ens hem plantejat estudiar l'estat funcional de la funció colinèrgica de tipus nicotínic del feix septohipocàmpic durant l'abstinència, avaluant l'efecte d'una injecció intraseptal de nicotina en la capacitat de l'animal alcohòlic per aprendre la resposta a la palanca durant l'abstinència d'alcohol (Experiment I). D'altra banda, s'ha estudiat la capacitat d'aprenentatge inhibitòri per tal de conèixer l'estat funcional i la implicació d'aquest circuit en el control de la conducta. Amb aquest objectiu, hem avaluat mitjançant aprenentatge de discriminació (amb estímuls excitatori i inhibitori), l'efecte d'una injecció intraseptal de nicotina en la capacitat d'inhibir una resposta en la Prova de Dos Estímuls de Pavlov i en l'extinció simple, en situació d'abstinència (Experiment II). Els resultats obtinguts en l'Experiment I mostren que l'abstinència d'alcohol modifica dràsticament, en sentit negatiu, la capacitat d'aprenentatge simple en els animals alcohòlics. D'altra banda, la nicotina té efectes oposats en els subjectes alcohòlics Abstinents i No-Abstinents, en aquests empitjora l'adquisició triplicant el temps necessari per assolir l'aprenentatge a la dosi de 10nM, mentre que en el cas dels Abstinents, neutralitza l'efecte disruptor de l'abstinència, en l'aprenentatge d'aquesta resposta, a la dosi de 20nM. Els subjectes alcohòlics No-Abstinents respecte dels controls mostren una sensibilització funcional a la nicotina administrada intraseptalment, que es fa palesa amb el desplaçament de la corba dosi-resposta cap a l'esquerre i amb un increment considerable de l'efecte màxim. Els resultats obtinguts en l'Experiment II mostren que l'abstinència té un efecte disruptor sobre el control inhibitori que és més pronunciat en els animals alcohòlics (sensibilització). Pel que fa a l'efecte de la nicotina en la Prova de Dos Estímuls de Pavlov, s'observa un efecte disruptor dosi-depenent en els alcohòlics No-Abstinents mentre que els Abstinents té l'efecte contrari, millorant el seu control inhibitori. Així doncs, la corba dosi-resposta per a la nicotina intraseptal pels animals alcohòlics Abstinents, respecte a la mateixa corba dels No-Abstinents, mostra la inversió del perfil de la nicotina i un desplaçament a l'esquerre (sensibilització) de l'efecte màxim. Els resultats obtinguts permeten concloure que els subjectes alcohòlics mostren una reactivitat exacerbada a l'administració de nicotina intraseptal, en comparació amb els controls. En l'abstinència d'alcohol, la resposta dels subjectes és molt diferent a la dels alcohòlics No-Abstinents, l'administració de nicotina "normalitza" la resposta dels Abstinents, equiparant-los als No-Abstinents injectats amb salí. Tot plegat és congruent amb una sensibilització funcional de la resposta colinèrgica de tipus nicotínic a l'acció concurrent de l'alcohol i la nicotina, en l'abstinència la nicotina pot substituir l'alcohol i neutralitzar-ne l'abstinència, aquestes propietats caracteritzen el cervell alcohòlic i el distingueixen del cervell control. Paraules clau: Consum crònic i voluntari d'alcohol; Abstinència; Nicotina; Septum medial. / The current knowledge about chronic alcohol consumption effect on the CNS is still limited. Despite to have identificated some of the changes that underlie phenomenons as tolerance and dependence, we still unknown the main mechanism responsible of addiction. Several studies have focused on GABAergic, glutamatergic, dopaminergic or serotoninergic transmission. These systems, whereas they become adapted by chronic alcohol, after an abstinence period their adaptation is reverted or compensed, for this reason, they could not be the main support of a permanent fenomenon as addiction. Previous studies, done with chronic alcohol drinking animals, have shown significant differences between alcohol and control groups in several excitatory and inhibitory learning processes. On the other hand, it has been identificated several physiologic and molecular changes in the nicotinic cholinergic transmission of these alcoholic animals. These changes, sensitization by up-regulation of the nicotinic receptor, are supposed to be irreversible. However, we unknow if these learning processes, and the underlying neural substratum, are also modificated during abstinence in these alcoholic animals. One of the main objectives of this thesis is to study the functional state of the nicotinic cholinergic function of the septo-hippocampal pathway during abstinence. For this purpose, we have evaluated the effect of an intraseptal injection of nicotine upon the acquisition and extinction of lever-press response during the alcohol abstinence (Experiment I). Furthermore, we have studied the acquisition of an inhibitory learning in order to know the implication and functional state of that pathway over behaviour control during withdrawal. For this purpose, after the acquisition of a discriminative learning (with excitatory and inhibitory stimulus), we have evaluated the effect of an intraseptal injection of nicotine on the capacity of the animal to inhibit a response, in the Pavlov's Two Stimuli Test and extinction session, during alcohol abstinence (Experiment II). Results obtained in Experiment I show that alcohol abstinence drastically impaired in the alcoholic animal the acquisition of a simple learning. On the other hand, nicotine has opposed effects in Abstinent and Non-Abstinent alcoholic animals. In Non-Abstinent subgroup, subjects that received nicotine 10nM show the worst acquisition, taking threefold more time to attain the criterion compared with saline subgroup, while in the case of the Abstinent, nicotine neutralizes the disruptive effect of abstinence at the dose of 20nM. The alcoholic Non-Abstinent animals compared with those of the control group show a functional sensitization to the intraseptal nicotine with an inverted U-shaped dose-response curve that appears shifted leftwards and with a significative increase of the maximum effect. Results obtained in Experiment II show that abstinence has a disruptive effect over the inhibitory control that is more pronounced in alcoholic animals (sensitization). Regarding nicotine effect in Pavlov's Two Stimuli Test, we observe a dose-dependent disruptive effect in Non-Abstinent subgroup while in the case of Abstinent it has the opposite effect improving their inhibitory control. The dose-response curve for the intraseptal nicotine injection in the Abstinent alcoholic animals compared to the same curve for the Non-Abstinent, shows an inverted U-shaped dose-response curve that appears shifted leftwards (sensitization). Overall results show that alcoholic subjects have an exacerbated reactivity to the intraseptal nicotine when compared to the control group. During alcohol abstinence, the response of that subjects is significantly different of that one of the Non-Abstinent, while the nicotine administration "normalizes" the Abstinent animals response equaling them to the Non-Abstinent injected with saline. All these results are congruent with a functional sensitization of the nicotinic cholinergic response to the concurrent action of alcohol and nicotine. During abstinence nicotine seems to substitute the alcohol and to neutralize the abstinence caused by that drug. Those properties would characterize the alcoholic brain and would distinguish it from the control one, implications for pharmacological therapies are discussed. Keywords: Chronic voluntary alcohol; Withdrawal; Nicotine; Medial septum.

Sammanfattning Syfte: Syftet med den här studien var att undersöka den upplevda effekten av upprepad behandling med kinesiotejp under 2 veckor, sett till smärta och besvär hos idrottare med medialt tibiasyndrom (MTS). Frågeställningarna som ställdes var: vilken effekt har behandling med kinesiotejp på smärta vid MTS samt vilken effekt har behandling med kinesiotejp på besvär och symtom vid medialt MTS? Metod: Femton personer med diagnosen MTS deltog i studien (10 kvinnor och 5 män). Samtliga deltagare var aktiva inom friidrott alternativt löpning. Deltagarna skattade sin smärta i båda benen, men endast ett ben tejpades. En lottning utfördes för att fastställa vilket ben som skulle behandlas med kinesiotejp. De med smärta i enbart ett ben tejpades på det benet som var symtomgivande. Deltagarna tejpades vid 2 tillfällen, de tejpades vid det första mötet och tejpen fick sedan sitta kvar i 6 dagar. Den sjätte dagen tog deltagarna själva bort tejpen och dagen efter utfördes samma tejpning igen. Sex dagar senare togs tejpen bort och efter 2 veckor utan tejp skickades en uppföljningsenkät ut. Deltagarna skattade upplevd smärta och besvär i båda benen på en visuell analog skala (VAS) vid första mötet och en uppföljning av smärta och besvär gjordes efter 1, 2 och 4 veckor. De fick också uppge upplevd symtomförändring efter 1, 2 och 4 veckor. Resultat: Upplevd smärta och besvär mätt på VAS-skalan visade ingen signifikant förändring över tid mellan det tejpade benet och det otejpade benet. Vid första uppföljning upplevde dock 12 av 15 (80 %) en symtomförbättring i sitt tejpade ben, medan 2 av 12 (16,7 %) upplevde en förbättring i sitt otejpade ben (p<0,05). En tendens till upplevd förbättring fanns vid uppföljning vid vecka 2: 9 av 15 (60 %) upplevde en förbättring på sitt tejpade ben medan 3 av 12 (25 %) upplevde en förbättring på sitt otejpade ben (p=0,57). Slutsats: Resultatet i denna studie visade att behandling med kinesiotejp kunde minska upplevda symtom hos idrottare med MTS den första veckan efter applicering. En tendens till minskning av upplevda symtom kunde även ses vid uppföljning efter 2 veckor med behandling av kinesiotejp. Ingen ytterligare effekt kunde ses efter borttagning av tejpen. Denna omedelbara effekt visar att kinesiotejp kan vara en möjlig behandlingsmetod för idrottare med MTS. Nyckelord: medialt tibiasyndrom, MTS, kinesiotejp, idrottare, överbelastningsskada / Abstract Aim: The purpose of this study was to examine the perceived effect of repeated treatment with kinesiotape during 2 weeks, in terms of pain and symptoms in athletes with medial tibial stress syndrome (MTSS). The research questions were: what effect does treatment with kinesiotape has in pain of MTSS and what effect does treatment with kinesiotape has in pains and symptoms of MTSS? Method: Fifteen people diagnosed with MTSS participated in the study (10 women and 5 men). All participants were track- and-field athletes or runners. The participants estimated their pain in both legs, but only one leg was taped. A lottery was conducted to determine which leg was to be treated with kinesiotape. Those with pain in only one leg were taped to the leg that was symptomatic. Participants were taped on 2 occasions, they were taped in the first meeting and the tape was then left for 6 days. On the sixth day the participants took the tape off and the following day they were taped again. Six days later, the tape was removed and after 2 weeks without tape a follow-up survey was sent. Participants estimated perceived pain and symptoms in both legs on a visual analogue scale (VAS) at the first meeting and follow-ups of pain and symptoms were made after 1, 2 and 4 weeks. They also estimated perceived change in symptoms after 1, 2 and 4 weeks. Results: Perceived pain and symptoms as measured on VAS revealed no significant change over time between the taped leg and the non-taped leg. At the first follow-up however, 12 of 15 (80%) experienced an improvement in symptoms in the taped leg, while 2 of 12 (16.7%) experienced improvement in their non-taped legs (p<0.05). A tendency to perceived improvement was found at follow-up in week 2: 9 of 15 (60%) experienced an improvement in their taped legs while, 3 of 12 (25%) experienced an improvement in their non-taped leg (p=0.57). Conclusions: The result of this study showed that treatment with kinesiotape decreased perceived symptoms in athletes with MTSS in the first week after application. A trend for reduction of perceived symptoms could also be seen at follow-up after 2 weeks of treatment with kinesiotape. No further effect was seen after removal of the tape. This immediate effect showed that kinesiotape may be a possible treatment for athletes with MTSS. Key words: medial tibial syndrome, MTSS, athletes, overuse injury.

Adaptive reproductive behavior requires the ability to recognize and approach possible mating partners in the environment. Syrian hamsters (Mesocricetus auratus) provide a useful animal model by which to study the neural processing of sexual signals, as mate recognition in this species relies almost exclusively on the perception of social odors. In the laboratory, male hamsters prefer to investigate female odors compared to male odors, and this opposite-sex odor preference provides a sensitive measure of the underlying neural processing of sexual stimuli. In addition to chemosensory cues, reproductive behavior in hamsters also requires sufficient levels of circulating gonadal steroid hormones, which reflect the reproductive state of the animal. These chemosensory and hormone signals are processed within an interconnected network of ventral forebrain nuclei, and within this network, the posteromedial cortical amygdala (PMCo) and medial amygdala (MA) are the only nuclei that both receive substantial chemosensory input and are also highly sensitive to steroid hormones. Although a large body of evidence suggests that the MA is critical for generating attraction to sexual odors, the specific role of the PMCo in regulating odor-guided aspects of male reproductive behavior has never been directly tested. Furthermore, detailed analyses of the MA suggest that separate, but interconnected sub-regions within this nucleus process odors differently. Specifically, the anterior MA (MeA) receives the majority of chemosensory input and responds to a variety of social odors, whereas the posterodorsal MA (MePD) receives less chemosensory input but contains the vast majority of steroid receptors. In order to further elucidate how the PMCo and/or MA process sexual odors, this dissertation addressed the following research questions: (1) Is the PMCo required for the expression of either opposite-sex odor preferences or male copulatory behavior? (2) Are functional interactions between MeA and MePD required for the expression of opposite-sex odor preferences? (3) How do MeA and MePD regulate odor responses within the MePD and MeA, respectively? (4) Are odor and/or hormone cues conveyed directly between MeA and MePD? Together, these experiments provide a comprehensive analysis of the functional and neuroanatomical substrates by which the brain processes sexual odors and generates appropriate behavioral responses to these stimuli.

Due to its significance in many cellular functions, fatty acid binding protein 7 (FABP7) has become a rising topic of interest for many scientists. Immunocytochemistry was used to map the distribution of FABP7 and test whether the amount of FABP7 immunoreactivity (FABP7-IR) differed in animals that were defeated in a fight, as compared to control animals that did not engage in any social interaction. The male green anole was used as the subject because its natural tendency to establish social classes within its species provides an ideal model to observe for variation in FABP7-IR. The results showed FABP7-IR in cells and fibers of the cortex, hypothalamus, thalamus, medial preoptic area, dorsoventricular ridge, amygdala, suprachiasmatic nucleus, nucleus accumbens, nucleus rotundus, habenular area, tectum, dorsal noradrenergic and lateral forebrain bundles, and lining the third and lateral ventricles. Qualitative observation suggested higher FABP7 levels in socially defeated males than controls in all areas.

<p>Forebrain cholinergic projection systems innervate the entire cortex and hippocampus. These cholinergic systems are involved in a wide range of cognitive and behavioral functions, including learning and memory, attention, and sleep-waking modulation. However, the <italic>in vivo</italic> physiological mechanisms of cholinergic functions, particularly their fast dynamics and the consequent modulation on the hippocampus and cortex, are not well understood. In this dissertation, I investigated these issues using a number of convergent approaches.</p><p> First, to study fast acetylcholine (ACh) dynamics and its interaction with field potential theta oscillations, I developed a novel technique to acquire second-by-second electrophysiological and neurochemical information simultaneously with amperometry. Using this technique on anesthetized rats, I discovered for the first time the tight <italic>in vivo</italic> coupling between phasic ACh release and theta oscillations on fine spatiotemporal scales. In addition, with electrophysiological recording, putative cholinergic neurons in medial setpal area (MS) were found with firing rate dynamics matching the phasic ACh release. </p><p> Second, to further elucidate the dynamic activities and physiological functions of cholinergic neurons, putative cholinergic MS neurons were identified in behaving rats. These neurons had much higher firing rates during rapid-eye-movement (REM) sleep, and brief responses to auditory stimuli. Interestingly, their firing promoted theta/gamma oscillations, or small-amplitude irregular activities (SIA) in a state-dependent manner. These results suggest that putative MS cholinergic neurons may be a generalized hippocampal activation/arousal network. </p><p> Third, I investigated the hypothesis that ACh enhances cortical and hippocampal immediate-early gene (IEG) expression induced by novel sensory experience. Cholinergic transmission was manipulated with pharmacology or lesion. The resultant cholinergic impairment suppressed the induction of <italic>arc</italic>, a representative IEG, suggesting that ACh promotes IEG induction. </p><p> In conclusion, my results have revealed that the firing of putative cholinergic neurons promotes hippocampal activation, and the consequent phasic ACh release is tightly coupled to theta oscillations. These fast cholinergic activities may provide exceptional opportunities to dynamically modulate neural activity and plasticity on much finer temporal scales than traditionally assumed. By the subsequent promotion of IEG induction, ACh may further substantiate its function in neural plasticity and memory consolidation.</p> / Dissertation

No description available.

Decades of research have demonstrated that people sometimes provide self-evaluations that emphasize their most flattering qualities. Different theoretical accounts have been offered to explain the mechanisms underlying positively-biased self-evaluation. Some researchers theorize that positively-biased self-evaluations arise from a self-protection motivation because positivity biases increase in situations of heightened self-esteem threat. Alternative views question whether self-protection motivation is a necessary or even dominant source of positivity bias by demonstrating that positively-biased self-evaluations occur even when threat is not heightened, and that a general judgment approach leads to positivity biases in some domains but also to negativity biases in other domains. One reason for this gap in knowledge is that behavioral measures are limited in their ability to resolve whether the processes underlying positively-biased self-evaluation are the same or different depending on contextual motivators. Neuroimaging methods are well suited to examine whether different mechanisms underlie similar behaviors, specifically similar positively-biased responses in different contexts. The four studies presented here explore the neural mechanisms of positively-biased self-evaluation by first identifying a core set of neural regions associated with positivity bias (Study 1A and 1sB), examining whether a heightened self-protection motivation changes the engagement of those neural systems (Study 2), and specifying the precise mechanisms supported by those regions (Study 3). Studies 1A and 1B revealed evidence for a neural system comprised of medial and lateral orbitofrontal cortex (OFC) and, to a lesser extent dorsal anterior cingulate (dACC) that was modulated by positivity bias. Study 2 found that a heightened self-protection motivation changes the engagement of medial OFC in positively-biased self-evaluation. Finally, Study 3 found evidence that medial OFC may support a common mechanism in positively-biased judgment that is implemented differently as a function of the motivational context. Taken together, these studies represent a first step toward developing a neural model of positively-biased self-evaluation. The findings provide some preliminary evidence that positivity biases may represent distinct processes in different motivational contexts. This dissertation sets the stage for future work to examine how specific positively-biased cognitive mechanisms may be supported by specific neural systems and computations as a function of motivational contexts. / text

The salience of natural or drug-associated reward is mediated by phasic dopamine (DA) release in the nucleus accumbens (NAc) arising from DAergic cells in the ventral tegmental area (VTA). Circulating sex steroid hormones can modulate reward associated with drugs of abuse; yet, it still remains unclear which brain regions are responsible for this modulation. The medial preoptic area (mPOA) is a hypothalamic brain area involved in the expression of naturally rewarding behaviors as well as the regulation and reception of circulating sex steroid hormones in female rats. Considering its role in regulating naturally rewarding behaviors, its well-established anatomical connectivity with the VTA, and its responsiveness to circulating sex steroid hormones, the mPOA is an ideal neural node through which hormones could modulate the rewarding facets of drugs of abuse. Here I show that preoptotegmental efferents to the VTA are primarily GABAergic, that they appose putative DAergic cell bodies in the VTA that project to the NAc, and that they are capable of responding to sex steroid hormones and changes in DA release. Furthermore, cocaine influences neural activity in mPOA efferents that project to the VTA. Removal of the mPOA also enhanced cocaine-induced locomotion, Fos-immunoreactivity in the mesolimbic reward system, DA release in the NAc, and augmented conditioned place preference. Together these findings suggest that the mPOA modulates the release of DA in the mesolimbic reward circuitry via inhibitory connections with DA neurons residing in the VTA, and sex steroid hormones, in turn, may act in the mPOA to modulate response to cocaine. / text