Imaging the stressed brain : elucidating the time- and region-specific effects of stress hormones on brain function : a translational approach

Contains fulltext : 100904.pdf (publisher's version ) (Open Access)Radboud Universiteit Nijmegen, 17 april 2013Promotores : Fernandez, G.S.E., Joëls, M. Co-promotor : Wingen, G.A. van299 p

Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure

Contains fulltext : 175071.pdf (publisher's version ) (Open Access)Exposure to stress during critical periods in development can have severe long-term consequences, increasing overall risk on psychopathology. One of the key stress response systems mediating these long-term effects of stress is the hypothalamic-pituitary-adrenal (HPA) axis; a cascade of central and peripheral events resulting in the release of corticosteroids from the adrenal glands. Activation of the HPA-axis affects brain functioning to ensure a proper behavioral response to the stressor, but stress-induced (mal)adaptation of the HPA-axis' functional maturation may provide a mechanistic basis for the altered stress susceptibility later in life. Development of the HPA-axis and the brain regions involved in its regulation starts prenatally and continues after birth, and is protected by several mechanisms preventing corticosteroid over-exposure to the maturing brain. Nevertheless, early life stress (ELS) exposure has been reported to have numerous consequences on HPA-axis function in adulthood, affecting both its basal and stress-induced activity. According to the match/mismatch theory, encountering ELS prepares an organism for similar ("matching") adversities during adulthood, while a mismatching environment results in an increased susceptibility to psychopathology, indicating that ELS can exert either beneficial or disadvantageous effects depending on the environmental context. Here, we review studies investigating the mechanistic underpinnings of the ELS-induced alterations in the structural and functional development of the HPA-axis and its key external regulators (amygdala, hippocampus, and prefrontal cortex). The effects of ELS appear highly dependent on the developmental time window affected, the sex of the offspring, and the developmental stage at which effects are assessed. Albeit by distinct mechanisms, ELS induced by prenatal stressors, maternal separation, or the limited nesting model inducing fragmented maternal care, typically results in HPA-axis hyper-reactivity in adulthood, as also found in major depression. This hyper-activity is related to increased corticotrophin-releasing hormone signaling and impaired glucocorticoid receptor-mediated negative feedback. In contrast, initial evidence for HPA-axis hypo-reactivity is observed for early social deprivation, potentially reflecting the abnormal HPA-axis function as observed in post-traumatic stress disorder, and future studies should investigate its neural/neuroendocrine foundation in further detail. Interestingly, experiencing additional (chronic) stress in adulthood seems to normalize these alterations in HPA-axis function, supporting the match/mismatch theory

Delayed Effects of Corticosterone on Slow After-Hyperpolarization Potentials in Mouse Hippocampal versus Prefrontal Cortical Pyramidal Neurons

Contains fulltext : 136243.pdf (publisher's version ) (Open Access)The rodent stress hormone corticosterone changes neuronal activity in a slow and persistent manner through transcriptional regulation. In the rat dorsal hippocampus, corticosterone enhances the amplitude of calcium-dependent potassium currents that cause a lingering slow after-hyperpolarization (sAHP) at the end of depolarizing events. In this study we compared the putative region-dependency of the delayed effects of corticosterone (approximately 5 hrs after treatment) on sAHP as well as other active and passive properties of layer 2/3 pyramidal neurons from three prefrontal areas, i.e. the lateral orbitofrontal, prelimbic and infralimbic cortex, with the hippocampus of adult mice. In agreement with previous studies, corticosterone increased sAHP amplitude in the dorsal hippocampus with depolarizing steps of increasing amplitude. However, in the lateral orbitofrontal, prelimbic and infralimbic cortices we did not observe any modifications of sAHP amplitude after corticosterone treatment. Properties of single action potentials or % ratio of the last spike interval with respect to the first spike interval, an indicator of accommodation in an action potential train, were not significantly affected by corticosterone in all brain regions examined. Lastly, corticosterone treatment did not induce any lasting changes in passive membrane properties of hippocampal or cortical neurons. Overall, the data indicate that corticosterone slowly and very persistently increases the sAHP amplitude in hippocampal pyramidal neurons, while this is not the case in the cortical regions examined. This implies that changes in excitability across brain regions reached by corticosterone may vary over a prolonged period of time after stress

Stressed memories: how acute stress affects memory formation in humans.

Contains fulltext : 81492.pdf (publisher's version ) (Open Access)Stressful, aversive events are extremely well remembered. Such a declarative memory enhancement is evidently beneficial for survival, but the same mechanism may become maladaptive and culminate in mental diseases such as posttraumatic stress disorder (PTSD). Stress hormones are known to enhance postlearning consolidation of aversive memories but are also thought to have immediate effects on attentional, sensory, and mnemonic processes at memory formation. Despite their significance for our understanding of the etiology of stress-related mental disorders, effects of acute stress at memory formation, and their brain correlates at the system scale, remain elusive. Using an integrated experimental approach, we probed the neural correlates of memory formation while participants underwent a controlled stress induction procedure in a crossover design. Physiological (cortisol level, heart rate, and pupil dilation) and subjective measures confirmed acute stress. Remarkably, reduced hippocampal activation during encoding predicted stress-enhanced memory performance, both within and between participants. Stress, moreover, amplified early visual and inferior temporal responses, suggesting that hypervigilant processing goes along with enhanced inferior temporal information reduction to relay a higher proportion of task-relevant information to the hippocampus. Thus, acute stress affects neural correlates of memory formation in an unexpected manner, the understanding of which may elucidate mechanisms underlying psychological trauma etiology

Fear bradycardia and activation of the human periaqueductal grey

Item does not contain fulltextAnimal models of predator defense distinguish qualitatively different behavioral modes that are activated at increasing levels of predation threat. A defense mode observed at intermediate threat levels is freezing: a cessation of locomotion that is characterized by a parasympathetically dominated autonomic nervous system response that causes heart rate deceleration, or fear bradycardia. Studies in rodents have shown that freezing depends on amygdalar projections to the periaqueductal grey (PAG). In humans, freezing-like behaviors are implicated in development and maintenance of psychopathology, but neural mechanisms underlying freezing or its characteristic autonomic response profile have not been identified. Here, we combined event-related blood oxygenation level-dependent functional MRI (BOLD-fMRI) with autonomic response measures in a picture viewing paradigm to probe activity and interconnectivity within the amygdala-PAG pathway and test for an association with parasympathetic as opposed to sympathetic activation. In response to negatively arousing pictures, we observed parasympathetic (bradycardia) and sympathetic (pupil dilation) autonomic responses, BOLD responses in the amygdala and PAG, and effective connectivity between these regions. Critically, BOLD responses in the PAG to negative pictures correlated on a trial-by-trial basis with bradycardia but not pupil dilation. This correlation with bradycardia remained significant when partialling out pupil dilation. Additionally, activity in regions associated with motor planning and inhibition mirrored the PAG response. Thus, our findings implicate the human PAG in a parasympathetically dominated defense mode that subserves a state of attentive immobility. Mechanistic insight into this qualitatively distinct defense mode may importantly advance translational models of anxiety disorders.10 p

Årsredovisning 2005 : Linköpings universitet

I slutet av 2005 kom beskedet att Stiftelsen för Strategisk Forskning satsar på tre centers of excellence vid LiU. En satsning som tar sin utgångspunkt i forskargrupper som levererar internationell spetsforskning samtidigt som de bedöms vara strategiskt viktiga för Sverige. Tre centers av 18 är en mycket god utdelning och ett kvitto på vår förmåga att bedriva spetsforskning med hög samhällelig relevans. LiU-forskare nådde framgångar också på många andra arenor under året. I en utvärdering av svensk fysikforskning lyftes flera forskargrupper vid LiU fram. Det är ingen tvekan om att vi i IFM har en av landets starkaste fysikinstitutioner. Utdelningen från forskningsråden blev god, och Vinnova satsade på ett s.k. Vinnex-center, Helix, om rörlighet i arbetslivet som ett sätt att främja hälsa och utveckling. En satsning som är intressant inte minst för att den engagerat flera av regionens största arbetsgivare. Inom forskarutbildningen tangerar vi 2003 års rekordnotering med 168 doktorsexamina. Det kommer förmodligen att stå sig ett tag. Vi ser sedan något år tillbaka en minskad antagning till forskarutbildning. Inte på grund av minskat intresse utan ändrade finansieringsmöjligheter, delvis till följd av ändrade strategier hos forskningsfinansiärerna. Det är inte säkert detta är enbart av ondo, det har inom vissa områden funnits tendenser till överproduktion i förhållande till vad arbetsmarknaden, inom och utanför akademin kan svälja. Grundutbildningen visar genomgående upp mycket goda resultat. 3 447 examina är det största antalet någonsin, på fyra år har antalet examinerade ökat med 50 procent. Studenternas produktivitet har ökat vilket gör att vi trots 100 färre studenter och ett utökat utbildningsuppdrag når takbeloppet med råge. Och studenterna är eftertraktade. I Högskoleverkets stora analys av studenternas etablering på arbetsmarknaden kommer LiU ut som klar etta av de stora universiteten. Även om söktrycket till flertalet utbildningar fortfarande är gott finns det vissa tendenser till en vikande rekrytering samtidigt som vi ser en hårdnande konkurrens om de nya studenterna. Vi behöver bli ännu bättre på att utveckla och marknadsföra utbildningar attraktiva för studenter med skilda behov, förutsättningar och ambitioner. Bokslutet slutade med ett överskott på 40 mkr, främst till följd av de goda prestationerna inom grundutbildningen och bantade personalkostnader. Det har varit en process som ställt tuffa krav på institutioner och andra enheter. Men det har varit nödvändigt och vi har varit framgångsrika. Vi behöver den handlingsfrihet som en ekonomi under kontroll ger. Högskolan står inför en period av stora förändringar, spelplanen ändras i viktiga avseenden. Den grundläggande utbildningen görs om inom ramen för den s.k.Bolognaprocessen, vi får ändrade villkor för utländska studenter (utanför EES-området) och det ställs ökade krav på universiteten att engagera sig i kommersialisering av forskningsresultat, för att nu nämna något av det som kommer att påverka oss de närmaste åren. För att möta detta har vi vid LiU tagit ett antal strategiska initiativ. Vi har lagt fast nya strategier för rekrytering av forskare och lärare och för internationalisering, vi har tagit viktiga initiativ för att stärka vår externa finansiering och initierat en översyn av institutionsstrukturen. Åtgärder som tillsammans med en ekonomi under kontroll och en stark verksamhet inom både utbildning och forskning gör att det finns anledning att blicka framåt med tillförsikt