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Visam pasaulyje stebimos tendencijos ieškinių dėl gydymo metu patirtos žalos daugėjimo, kurios neabejotinai palies ir Lietuvą. Gydytojų ir paciento santykių institutas formavosi įtakojamas etikos, teisės ir medicinos mokslų. Šių mokslų specifikos nepakankamas įvertinimas, sprendžiant gydytojų civilinės atsakomybės klausimus, kaip ir netinkamas šių santykių teisinis reguliavimas ir teismų formuojama teisės normų aiškinimo praktika, žinomi, kaip svarbiausi veiksniai įtakojantys „gynybinės medicinos“ praktikavimą, darantį didelę žalą sveikatos priežiūros sistemos finansiniams ištekliams ir sukeliantį papildomos žalos riziką pacientams. Gynybinę mediciną nuo rūpestingo ir atidaus gydytojo pareigos vykdymo skiria labai plona ir lengvai peržengiama linija. Lietuvoje esantis sveikatos priežiūros paslaugų teisinio reguliavimo nenuoseklumas, vieningo gydytojų etikos kodekso nebuvimas, neįgyvendinta bendrų diagnostikos ir gydymo metodikų koncepcija, sukelia teorinį pavojų atsirasti naujoms civilinės atsakomybės taikymo problemoms. Teismų praktikoje įtvirtintas maksimaliai atidaus, rūpestingo ir kvalifikuoto gydytojo elgesio standartas, vertinant jį pasaulinės teismų praktikos ir medicinos specifikos požiūriu, turi būti keistinas, kaip nustatantis nerealius ir neįgyvendinamus kriterijus, galinčius tapti pagrindu neteisingam gydytojų civilinės atsakomybės taikymui. Skirtingai nuo aiškių kriterijų vertinant paciento informavimo institutą, priežastinio ryšio nustatymas, bylose dėl gydytojų... [toliau žr. visą tekstą] / All over the world we observe a tendency for the increase of claims for damages of treatment that will with no doubt come to Lithuania. The establishment of the institute of doctor and patient was influenced by the science of ethics, law and medicine. The fact that these sciences were underestimated when discussing doctors’ liability as well as improper legal regulation and explanation of normative legal acts formed by courts are the main factors that brought “defensive medicine” in practice, that makes a lot of harm to the formation of the health care system financial recourses and puts the patients in the risk of getting additional damage. Thoughtful and attentive doctors’ duties and “defensive medicine” is separated by a hairline which is easy to trespass. The incoherence of the health care legal regulations in Lithuania, the non-existence of united doctors’ ethic code, the unfulfilled concept of diagnosis and treatment bring a danger of emerging new problems in applying the civil liability. A standard of most attentive, careful and qualified doctor treatment is established in court practice. It has to change taking into consideration the worldwide court practice and particularities of medicine as that sets unrealistic and impracticable criteria, which makes base for misapplication of doctors’ civil liability. Differently from the clear criteria for the evaluation of the institute of patient information, the establishment of causality in cases of doctors’ civil liability... [to full text]

Bakalauro baigiamajame darbe atliekamas vadovo bendravimo su pavaldiniais vertinimas paslaugų sektoriuose (Šiaulių miesto valyklose, viešbučiuose, Šiaulių ir Norvegijos skalbyklose). Klausimynas, pagal kurį atlikta darbuotojų apklausa tiriamų paslaugų sektorių įmonėse, parengtas remianti vadybinės literatūros autorių (Jasinavičius, Sokol, 2005; Kasiulis, Barvydienė, 2005; Baršauskienė, Janulevičiūtė, 1999) išskirtomis asmeninėmis vadovo savybėmis, originaliu Costigan ir Schmeidler sudarytu bendravimo klimato (CCI) klausimynu bei lietuvių autorių (Bakanauskienė, Petkevičiūtė, 2003; Misevičius, Urbonienė, 2006) išskirtais bendravimo trukdžiais. Apklausoje dalyvavo 181 respondentų (63 – viešbučių darbuotojų, 65 – valyklos, 26 – Šiaulių skalbyklos, 27 – Norvegijos skalbyklos). Tyrimo metu nustatyta, kad visuose paslaugų sektoriuose išryškėjo trys darbuotojams imponuojančios vadovo asmeninės savybės: santykių šiltumas, nuoširdumas, empatija. Tiriamose paslaugų sferose dominuoja palaikantis bendravimo klimatas, tačiau yra ir gynybinio bendravimo klimato apraiškų. Palaikantį bendravimo klimatą labiausiai stiprina tokie veiksniai kaip „problemų įvardinimas darbuotojams“, „vadovo pagarbus elgesys su pavaldiniais“ ir „vadovo aiškus ir objektyvus situacijos apibūdinimas“. Tuo tarpu gynybinio bendravimo klimato raišką labiausiai stiprina „vadovo asmeninės pozicijos pabrėžimas“ ir per didelis „vadovo asmeninės atsakomybės prisiėmimas už darbo rezultatus“. Tiriamuose paslaugų sektoriuose... [toliau žr. visą tekstą] / The aim of the paper is to compare supervisor - employee communication patterns in a different type of service providing organizations (laundries, hotels in Šiauliai, Šiauliai washhouse, Norway washhouse). Framework of this study is the personal supervisor characteristics, offered by managerial literature authors (Jasinavičius, Sokol, 2005; Kasiulis, Barvydienė, 2005; Baršauskienė, Janulevičiūtė, 1999) original communication climate inventory (CCI) operationalized by J. I. Costigan and M. A. Schmeidler (1984) and communication barriers, offered by lithuanian authors (Bakanauskienė, Petkevičiūtė, 2003; Misevičius, Urbonienė, 2006). There were 181 respondents involved in this survey (63 - employees from Šiauliai hotels, 65 - employees from Šiauliai laundries, 26 - employees from Šiauliai washhouse, 27 - employees from Norway washhouse). The final results of the survey were grouped and interpreted as well as conclusions made. While carrying out the survey it was found out that sincerity, empathy, warm relationships are the most important personal supervisor characteristics. The results showed that supportive communication climate dominates in all service sectors, but there are some manifestations of the defensive communication climates as well. The most important factors of the supportive climate dominance in the organizations are that supervisors define clearly problems, treat with their employees with respect and characterize situation clearly and objective. The most important... [to full text]

本論文的中心命題是：冷戰後的中國是尋求向外擴張、還是自我防禦的國家？為了檢視此一命題，本論文從守勢現實主義（defensive realism）的理論中推論出維持現狀、嚇阻戰略與昂貴信號，以作為檢視冷戰後中共安全行為的指標。本論文分別檢視中共領導人的政策宣示、1995-96年台海危機以及冷戰後中共與南海爭議的個案，證明：第一、中共對國際環境的認知會符合守勢現實主義關於良性的國際結構與安全充足的觀點；第二、中共的外交政策旨在維持既有的國際秩序，所以其對外的行為以維持現狀為主，避免改變現狀的情形發生；第三、中共的國防政策屬於防禦性的，因此其戰略以嚇阻為主，避免使用武力直接與敵人衝突；第四、為了表示防禦性、維持現狀或者是合作的意圖，中共採取昂貴信號的作法，以避免被其他國家所誤解。所以，本論文論證出冷戰後的中國是一個追求自我防禦的國家，其安全政策是屬於防禦性的。 / The central question of this thesis is: Is China an expansionist or a self-preserving state in the Post-Cold War era? From defensive realism theory, I infer status quo policy, deterrence strategy, and costly signal to estimate Post-Cold War PRC security behavior. Empirically, I examine Chinese leaders’ statements, the Taiwan Strait crisis in 1995-96, and South China Sea disputes in the Post-Cold War era. I reach the conclusion that: First, PRC’s perception of international environment is consistent with defensive realism’s argument that international structure is benign and security is plentiful. Second, China engages status quo foreign policy to maintain the international order. Third, China’s defense policy emphasizes on deterrence strategy to avoid direct conflict with the enemy. Fourth, China adopted costly signals to unfold its defensive, status quo, or cooperative intention to prevent other countries’ misunderstanding. I argue that, therefore, Post-Cold War China is a self-protecting state with the defensive security policy.

Submitted by Ronildo Prado (ronisp@ufscar.br) on 2017-08-10T13:43:34Z No. of bitstreams: 1 TeseTS.pdf: 985479 bytes, checksum: 302b5555765b9106acb574df3f32a57c (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-08-10T13:43:42Z (GMT) No. of bitstreams: 1 TeseTS.pdf: 985479 bytes, checksum: 302b5555765b9106acb574df3f32a57c (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-08-10T13:43:49Z (GMT) No. of bitstreams: 1 TeseTS.pdf: 985479 bytes, checksum: 302b5555765b9106acb574df3f32a57c (MD5) / Made available in DSpace on 2017-08-10T13:43:56Z (GMT). No. of bitstreams: 1 TeseTS.pdf: 985479 bytes, checksum: 302b5555765b9106acb574df3f32a57c (MD5) Previous issue date: 2017-05-30 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Exposure of rodents to an open elevated plus maze (oEPM, an EPM with all four open arms) elicits antinociceptive responses, high level of plasma corticosterone and defensive behaviors. However, very little is known about the neural substrates and neurotransmitters that modulate the antinociceptive responses and the defensive behavior of oEPM-exposed animals. It is known that the amygdala plays an important role in the modulation of defensive behavior and pain responses. Accordingly, the Experiment 1 investigated the effects of chemical inactivation of the amygdala [through local injection of cobalt chloride (CoCl2: a nonspecific synaptic blocker)] on the nociception of mice injected formalin into the right hind paw (nociceptive test) and on the defensive behavior of oEPM-exposed mice. Results showed that the amygdala inactivation induced an antinociceptive response in mice injected formalin into the right hind paw when exposed to the glass-cage (safe situation). However, the antinociceptive response was not altered when mice were exposed to the oEPM (aversive situation). In addition, the mice amygdala inactivation reduced the time spent in the proximal area of the arms as well as the frequency of stretched attend postures (SAP), and increased time spent in the arm ends and the head-dipping frequency, suggesting an anxiolytic-like effect. Experiment 2 assessed the pattern of activation of the basolateral (BLA) and central (CeA) nuclei of the amygdala through quantification of Fos protein expression in mice exposed to the oEPM (aversive situation) or injected with formalin into the right hind paw. Fos-positive labeled cells were bilaterally increased in the amygdaloid complex, particularly in the BLA, compared to the control groups. Whereas the neuropeptide corticotropin-releasing factor (CRF) plays a role in the modulatory system of defensive and antinociceptive responses to aversive situations, the Experiment 3 investigated the effects of intra-amygdala microinjections of CRF1 antagonist (CP376395) on these responses on mice exposed to the oEPM. Results showed that the antinociceptive and defensive responses did not change by the blocked of CRF1 in the amygdala. These results are suggestive that the amygdala (in particular, its BLA nucleus) plays a role in the modulation of nociceptive response induced by formalin test and in the modulation of defensive behaviors in oEPM-exposed mice. / Camundongos expostos ao labirinto em cruz elevado aberto (LCEa: 4 braços abertos) exibem intensa resposta antinociceptiva, elevadas concentrações de corticosterona plasmática e comportamentos defensivos. Contudo, substratos e neurotransmissores envolvidos nas respostas antinociceptiva e comportamental eliciadas pela exposição ao LCEa ainda são pouco conhecidos. É possível que o complexo amidaloide esteja envolvido nestas respostas uma vez que destaca-se como uma das principais regiões encefálicas envolvidas no processamento de estímulos aversivos, nas respostas emocionais relacionadas ao medo e na modulação de dor. O presente estudo investigou se a inativação do complexo amidaloide, através da microinjeção de cloreto de cobalto, atenuaria a expressão tanto da dor provocada pelo teste de formalina na pata, como da antinocicepção e comportamentos defensivos de camundongos, sob estímulo nociceptivo ou não, expostos ao LCEa (Experimento 1). Os resultados mostraram que a inativação do complexo amidaloide promoveu um efeito antinociceptivo nos animais submetidos ao teste de formalina e expostos a caixa de vidro (ambiente seguro), porém, não alterou a resposta antinociceptiva e reações de defesa induzidos pela exposição ao LCEa (ambiente aversivo). Por outro lado, na ausência do estímulo nociceptivo, a inativação da amídala promoveu: redução no tempo de permanência dos camundongos nas regiões proximais dos braços do LCEa e na frequência total de SAP (stretched attend posture); e aumento na permanência nas extremidades do LCEa e na frequência de mergulhos (head-dipping), sugerindo efeito ansiolítico. O Experimento 2 teve como objetivo avaliar a ativação neuronal, através da quantificação de proteína Fos, do complexo amidalóide de camundongos submetidos ao teste da formalina na pata e de camundongos expostos ao LCEa. O conjunto de resultados desse experimento demonstrou que o estímulo nociceptivo e a exposição ao LCEa promoveram aumento da expressão de células positivas para a proteína Fos no complexo amidalóide, sobretudo no núcleo basolateral da amídala (BLA), sem haver diferença significativa entre os hemisférios direito e esquerdo. Visto que o CRF desempenha um papel na mediação de respostas defensivas e antinociceptiva eliciadas por estímulos aversivos, investigamos o papel do antagonista de CRF1 (CP376395) na amídala na modulação destas respostas eliciadas em camundongos expostos ao LCEa, sob estímulo nociceptivo ou não. Os resultados mostraram que a inibição dos receptores de CRF do tipo 1 da amídala, sob influência ou não da nocicepção, não alterou a antinocicepção e os comportamentos defensivos induzidos pela exposição ao LCEa. Os resultados sugerem que, independente de lateralização e da neurotransmissão CRF-érgica, a amídala, sobretudo o BLA, tem um papel importante na modulação das respostas nociceptivas induzidas pelo teste de formalina e nas respostas comportamentais de camundongos expostos ao LCEa. / FAPESP: 2014/02956-7

Les prairies subalpines abritent de grandes populations d’herbivores sauvages et sont souvent soumises au pâturage domestique. Le but de cette thèse est d’analyser la réponse métabolique des plantes subalpines à l’herbivorie, et d’identifier les conséquences fonctionnelles sur l’écosystème via la décomposabilité des litières. Pour cela, nous avons établi un dispositif d’exclusion des herbivores sur l’alpage d’Armenaz dans le massif des Bauges, dans deux contextes de pâturage différents : extensif par des herbivores sauvages (chamois, Rupicapra rupicapra) et intensif par des herbivores domestiques (génisses, Bos taurus). Nous avons caractérisé une vingtaine d’espèces végétales par des traits fonctionnels foliaires reflétant leur métabolisme de croissance et de défense, en présence ou en absence d’herbivores, et avons estimé la décomposabilité des litières de certaines d’entre elles. Contrairement à l’hypothèse du compromis entre croissance et défense, nos résultats montrent que la présence de composés de défense (polyphénols et lignine) chez les plantes n’est pas reliée à leur stratégie d’acquisition des ressources. Dans notre étude, la réponse des plantes à l’exclusion des herbivores dépend essentiellement : (1) du contexte d’herbivorie, la réponse étant d’avantage marquée dans le contexte du pâturage intensif par les génisses qu’extensif par les chamois, (2) des espèces végétales, suggérant l’existence de différentes stratégies de défense, (3) des conditions environnementales, pouvant être le reflet d’effets d’interaction avec le traitement d’herbivorie. Parmi les réponses observées, l’exclusion des herbivores entraîne chez certaines espèces une diminution de la teneur en composés phénoliques, et plus particulièrement en flavonoïdes, pouvant refléter la relaxation de la synthèse de ces composés de résistance en absence d’herbivores. L’exclusion des chamois n’influence pas la composition chimique des litières ni leur décomposabilité. Cette dernière, parmi les composés étudiés, dépend majoritairement de sa composition en polyphénols. L’identification d’effets contrastés de différents contextes d’herbivorie sur la réponse des plantes et des fonctions écosystémiques qui en découlent nous permet d’améliorer notre compréhension du fonctionnement des prairies subalpines. Ce sont autant d’éléments pour nous aider à mieux appréhender les effets sur l’environnement d’éventuels changements démographiques des populations de grands herbivores. / Alpine grasslands are home to large populations of wild herbivores and are often exposed to additional grazing by domestic herbivores. This study aims to investigate the metabolic response of subalpine plant species to herbivory and to identify the ecosystem functional consequences via the alteration of litter decomposability. For this purpose, we set up a two-year experimental design using exclosures on the Armenaz subalpine grassland from the Bauges massif, under two mammalian herbivory regimes: intensive grazing by domestic heifers (Bos taurus) and extensive grazing by wild chamois (Rupicapra rupicapra). We measured leaf functional traits representative of growth and defense metabolisms on about twenty plant species grown in presence or absence of herbivores, and estimated litter decomposability of some of these species. Contrary to the hypothesis of a growth/defense tradeoff, our results show that the allocation of defensive compounds (polyphenols and lignin) in plants is not related to their nutrient acquisition strategy. In our study, plant responses to grazing exclusion vary according to: (1) herbivory context, plant response being more pronounced in the case of intensive grazing by heifers than extensive grazing by chamois, (2) plant species, suggesting that they rely on different defensive strategies, (3) environmental conditions, which may reflect the interactive effects with grazing treatment. One of the observed responses of plants to grazing exclusion is the decrease of their phenolic content, and more specifically flavonoids, which can be explained by the relaxation of the production of plant defenses when herbivores are no longer present. Chamois exclusion has no influence on chemical composition and decomposability of litters, the latter being best explained by its phenolic content. Revealing the contrasted effects of wild and domestic mammalian herbivores on vegetation and related soil processes allow us to improve our understanding of subalpine grasslands functioning. This should help us to better predict the effects of potential demographic variations of herbivore populations on environment.

Our senses are constantly bombarded with information. How does the brain integrate such a variety of inputs to generate appropriate behaviours? Innate defensive behaviours are a good model to address this question. They are essential for animal survival and the brain circuits that control them are highly conserved across species. Moreover, the sensory inputs and behavioural outputs can be well defined and reliably reproduced in the lab. This allows us to study function of the individual components of the circuit controlling these behaviours. Ventromedial hypothalamus (VMH) is a key brain region for controlling responses to predators; it has been shown that inactivating the VMH can reduce defensive behaviours. Interestingly, activating the VMH output neurons (SF1+ cells) can produce a variety of different behaviours, from immobility to escape, depending on the intensity of activation. During my PhD I used a variety of approaches to address the question of the function of the VMH in control of defensive behaviours. At first I hypothesised that the VMH might act as a centre responsible for choosing an appropriate behavioural response according to the stimulus. I set to investigate how different activation levels of SF1+ neurons can produce such different behavioural outputs, and how this activity is modulated in vivo in response to predator stimuli. I began the project by quantifying mouse defensive behaviours in response to olfactory and auditory predator cues, as well as to the optogenetic activation of SF1+ neurons. I then questioned whether there was heterogeneity within the population of SF1+ neurons, which could explain their ability to trigger different behaviours. I performed patch clamp recordings from acute brain slices and conducted a study of the electrophysiological properties of SF1+ neurons. I next investigated how SF1+ neurons integrate excitatory inputs from the medial amygdala, a region which receives olfactory inputs from the accessory olfactory bulb. By combining optogenetics with slice electrophysiology and behavioural assessment, I described the physiology and relevance of this connection. Finally, I investigated in vivo activity in the VMH in response to predator cues by performing calcium imaging of the VMH neurons in freely moving mice. By presenting different sensory stimuli, I addressed the question of heterogeneity of the input pattern to the VMH neurons and the relationship between the VMH activity and the behavioural output. Taken all together, the results of this project have led to a hypothesis whereby the function of the VMH is to facilitate rather than directly control the choice of an appropriate behavioural response.

Orientador: Ricardo Nunes de Souza / Banca: Cleopatra da Silva Planeta / Banca: Hélio Zangrossi Junior / Banca: Marcus Lira Brandão / Banca: Francisco Silveira Guimarães / Resumo: Quando os animais são confrontados com estímulos ambientais ameaçadores como a exposição ao predador ou estímulos como altura, iluminação e estímulos nociceptivos, exibem reações de defesa coordenadas e específicas. Nas últimas décadas, observa-se um crescente interesse pela utilização de estímulos naturalísticos para o estudo das bases neurais de emoções como o medo e ansiedade. Nesse contexto, o teste de exposição ao rato (RET), um novo modelo etológico de interação presa-predador, utilizando camundongos (presa) e ratos (predador), foi desenvolvido para avaliar a expressão de diferentes comportamentos defensivos na presa. Entretanto, poucos estudos foram conduzidos com esse modelo no intuito de investigar as bases neurais das respostas defensivas de camundongos expostos ao rato. Adicionalmente, evidências da literatura destacam que o hipocampo ventral (HV) e o complexo amidalóide (CA) parecem contribuir diferencialmente na modulação de respostas defensivas frente a estímulos proximais (predador) ou potenciais. Assim, o presente estudo foi conduzido para investigar o papel do HV e do CA nas respostas defensivas de camundongos exibidas diante do predador (rato) e do contexto associado ao predador. Para tal, o presente estudo foi dividido em quatro etapas. Na primeira delas, investigamos se o estresse da exposição ao predador no RET altera a secreção de corticosterona em camundongos e determinamos a magnitude e a duração desta secreção. Na segunda etapa, avaliamos o papel do HV e do CA, através da injeção local do agonista de receptores GABAA muscimol (0,1 μg/0,1 μl), na mediação de respostas comportamentais defensivas de camundongos expostos ao RET (situação proximal) e comparamos com aquelas apresentadas durante a exposição ao labirinto em cruz elevado (LCE - situação potencial). Subsequentemente, investigamos se camundongos expostos... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: When animals are confronted with environmental threatening situations such as exposure to a predator as well as to height, high illumination and nociceptive stimuli they exhibit defensive behaviors. Over the past decades there has been a growing interest by the neuroscientists in the use of naturalistic stimuli to the study of the neural systems of the emotions such as fear and anxiety. In this context, the Rat Exposure Test (RET) which is a new ethological model of prey-predator interaction using mice (prey) and rats (predator) was developed in order to evaluate the expression of different defensive behaviors in the prey. However few studies using this model have been carried out with the objective of investigating the neural systems of the defensive behaviors in mice exposed to rats. In addition, evidence in literature has shown that the ventral hippocampus (VH) and the amygdaloid complex (AC) contribute differentially in the modulation of defensive behaviors during exposure to either potential or immediate stimuli (predator). Thus, the present study was aimed at investigating the role of VH and AC in the modulation of defensive behaviors of mice when exposed to predators (rats) as well as the predatory context. The experiment comprised four parts: (i) to investigate both whether stress regarding the exposure to the predator alters the corticosterone secretion in mice and to determine the magnitude and the duration of this secretion; (ii) the role of VH and AC was evaluated through local microinjection of the GABAA receptor agonist muscimol (0,1 μg/0,1 μl) in the modulation of defensive behavioral responses of mice exposed to RET (proximal aversive situation). The responses then were compared to those presented during to the exposure to the elevated plus-maze (EPM - potential aversive situation); (iii) to investigate whether mice exposed to natural predator (rat) in RET exhibit... (Complete abstract click electronic access below) / Doutor

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The research of neural mechanisms related to training of emotions has increased in recent years. Fear is a behavior originated in response to the dangers encountering by animals, originating in defensive responses displayed when exposed to threatening stimuli. Fear memory helps animals and humans recognize putative sources of danger and adopt the appropriate behavioral response. The primary neural circuits for fear acquisition and extinction involve connections between prefrontal cortex, ventral hippocampus and amygdala, and these áreas are modulated by brainstem networks. The nucleus (n.) incertus in the dorsal pontine tegmentum provides a strong GABAergic projection to these forebrain centers and is strongly activated by neurogenic stressors. In this study in male, adult rats, we injected miniruby anterograde tracer into n. incertus and delineated its projections to the amygdala; and examined the effect of electrolytic lesions of n. incertus on different stages of the fear conditioning-extinction process. N. incertus-derived nerve fibers were observed in anterior medial amygdala, endopiriform nucleus, intra-amygdala bed nucleus of stria terminalis, amygdalohippocampal transition area, and the ventromedial nucleus of the lateral amygdala, with a broad fiber band present between the basolateral amygdala and the olfactory nuclei of amygdala. In a conventional contextual fear conditioning paradigm, we compared freezing behavior in control (naïve) rats (n = 13), with that in rats after sham- or electrolytic lesions of n. incertus (n = 9/group). There were no differences between the three groups in the habituation, acquisition, or context conditioning phases; but n. incertus-lesioned rats displayed a markedly slower (delayed) extinction of conditioned freezing responses than sham/control rats; suggesting n. incertus-related circuits normally promote extinction through inhibitory projections to amygdala and prefrontal cortex. The results helps in understanding the neurobiological mechanisms involved and in development of the future biotechnological techniques to minimize the effects of disorders associated with fear in humans, such as panic, anxiety and posttraumatic stress disorder. / A pesquisa dos mecanismos neurais relacionados à formação das emoções tem crescido nos últimos anos. O medo é um comportamento originado em resposta aos perigos enfrentados pelos animais, tendo sua origem nas reações defensivas exibidas quando da exposição a estímulos ameaçadores. A memória do medo ajuda os animais e os seres humanos a reconhecem as fontes putativas de perigo e adotar a resposta comportamental apropriada. Os circuitos neurais primárias envolvidos nos mecanismo de aquisição de medo e extinção envolvem conexões entre o córtex pré-frontal, hipocampo ventral e a amígdala, e estas áreas são moduladas por redes do tronco cerebral. O núcleo incertus (NI) no tegmento dorsal pontino fornece uma forte projeção GABAérgica a estes centros prosencéfalicos e é fortemente ativado por estressores neurogênicos. Neste estudo em ratos adultos machos foi injetado o traçador anterógrado miniruby no NI, delineado as suas projeções para a amígdala e examinado o efeito de lesões eletrolíticas no NI sobre diferentes fases do processo de condicionamento do medo-extinção. Fibras derivadas do NI foram observadas na amígdala medial anterior, núcleo endopiriforme, parte intra-amígdala do núcleo do leito da estria terminalis, área de transição amígdala-hipocampal, e o núcleo ventromedial da amígdala lateral, com uma ampla faixa de fibra presentes entre a amígdala basolateral e os núcleos olfativos da amígdala. Em um paradigma de condicionamento contextual de medo convencional, comparou-se o comportamento de congelamento em ratos controle (não operados) (n = 13), com ratos operados sem lesão do NI e ratos com lesão do núcleo incertus (n = 9). Não houve diferenças entre os três grupos nas fases de habituação, aquisição ou condicionamento ao contexto, mas ratos com lesão no NI exibiram uma extinção nitidamente mais lenta (com atraso) de respostas condicionadas de congelamento em comparação com ratos operados sem lesão do NI e controles, sugerindo que circuitos NI relacionados normalmente promovem a extinção através de projeções inibitórias para a amígdala e o córtex pré-frontal. Os resultados encontrados auxiliam na compreensão dos mecanismos neurobiológicos envolvidos e no desenvolvimento futuro de técnicas terapêuticas biotecnológicas visando minimizar os efeitos dos distúrbios associados ao medo em humanos, a exemplo do pânico, ansiedade patológica e estresse pós-traumático.

Primeiramente, investigamos as respostas defensivas de animais lesionados da parte dorsal da PAG rostral durante o confronto predatório. Estes animais permaneciam com as respostas de avaliação de risco (AR) porem perdem as respostas de freezing. Em um segundo estudo, analisamos as respostas defensivas frente ao predador em animais lesionados da parte ventrolateral da PAG caudal. Estes animais perdem as respostas de freezing e aumentam as respostas de AR. Será que as respostas de AR dependem da integridade da parte dorsal rostral e ventrolateral caudal da PAG ? Por último, investigamos as respostas defensivas em animais com lesão combinada destas áreas. Observamos uma diminuição drástica das AR e um aumento das respostas exploratórias. Provavelmente, as respostas de AR estão sendo moduladas pela parte dorsal rostral e ventrolateral caudal da PAG através de seus alvos ascendentes hipotalâmicos, e estes com o septo lateral. As respostas de freezing parecem ser moduladas por projeções descendentes da PAG para a medula espinal. / First, we investigated the defensive responses of injured animals of the dorsal part of the rostral PAG during predatory confrontation. These animals remained with the risk assessment responses (AR) however lose the freezing of response. In a second study, we analyzed the defensive responses front predator injured animals in the ventrolateral part of the caudal PAG. These animals lose the responses of freezing and increase AR responses. Does the AR responses depend on the integrity of dorsal part rostral and caudal ventrolateral PAG? Finally, we investigated the defensive responses in animals with combined injury of these areas. We observed a dramatic decrease of AR and an increase in exploratory response. Probably AR responses are modulated by the dorsal part of the rostral and caudal ventrolateral PAG through its hypothalamic ascendant targets, and these with the lateral septum. Freezing responses appear to be modulated by descending projections from the PAG to the spinal cord.