Dopaminergic modulation of synaptic transmission and plasticity in the lateral amygdala

Fear conditioning is one of the most powerful and widely used paradigm to investigate the mechanisms of associative learning in animals (LeDoux, 2000; Maren, 2001). Behavioral and in vivo electrophysiological evidence indicate that induction of long-term-potentiation (LTP), a form of associative, activity-dependent synaptic plasticity in the lateral amygdala (LA), a brain structure tightly controlled by GABAergic inhibition, underlies the acquisition of fear conditioning (Lang and Pare, 1997; Pare et al., 2003). Dopamine (DA), the most abundant catecholemine in the brain, is released in the amygdala upon stress. DA receptor activation is required for the potentiation of sensory evoked neuronal activity in the LA during conditioning (Rosenkranz and Grace, 2002). Conversely, intra-amygdala injections of DA receptor antagonists prevents the acquisition of fear conditioning (Greba et al., 2001; Greba and Kokkinidis, 2000; Guarraci et al., 2000; Guarraci et al., 1999). The cellular and synaptic mechanisms underlying the dopaminergic modulation of fear conditioning and synaptic plasticity are, however, still unknown. In the first part of my work, I showed that DA gates the induction of LTP in the mouse LA by supressing feed-forward inhibition mediated by local interneurons. The action of DA on synaptic plasticity depended on the activation of D2 receptors and appeared to be twofold. First, it reduced the quantal content at inhibitory synapses, thereby decreasing inhibitory synaptic transmission and second, it facilitated inhibition onto interneurons by depolarizing interneurons involved in disinhibition. In the second part of my work I investigated the role of DA on spontaneous inhibitory network activity. Consistent with previous in vivo data showing that systemic administration of DA agonists in the LA increases the spontaneous firing of interneurons (Rosenkranz and Grace, 1999), we found that bath application of DA increased the frequency of spontaneous inhibitory transmission recorded from projection neurons. In contrast to the gating of LTP, this effect required the activation of D1 and D2 receptors in synergy. Preliminary data suggested that the D1 receptor-mediated increase in spontaneous inhibitory transmission did not involve cAMP-mediated intracellular signaling mechanisms

Les romans de Marie-Jeanne Riccoboni: variations sur le "texte de l'héroïne"

Marie-Jeanne Riccoboni 's novels, published between 1757 and 1776, contain a number of emphases that differentiate them from feminocentric novels by eighteenth-century male writers. Some emphases are thematic: Riccoboni stresses the woman's active participation in the love affair, and she questions the binary oppositions conqueror/conquered, strong sex/weak sex. Other emphases contribute even more to undermining the "heroine's text": the heroine's destiny is determined not only by her sexual behavior, but also by friendship, and it does not always conform to the traditional marriage/death dichotomy.Les romans de Marie-Jeanne Riccoboni, publiés entre 1757 et 1776, contiennent une série de variations qui les différencient des romans féminocentriques masculins du dix-huitième siècle. Variations thématiques: participation active de la femme dans la relation amoureuse, remise en question des oppositions conquérant/conquise, sexe faible/sexe fort. Variations qui minent davantage le "texte de l'héroïne": influence de l'amitié, et pas seulement du comportement sexuel, sur la destinée de la protagoniste; remise en question de la fin traditionnelle mariage/mort par une structure plus ouverte et par des déplacements qui engagent à reconsidérer l'adéquation entre mariage et bonheur

Saints and lovers: myths of the avant-garde in Michel Georges-Michel's Les Montparnos

This article examines Michel Georges-Michel’s 1924 novel Les Montparnos as a study of the myths circulating around the Montparnasse avant-garde of the 1920s, and their function in relation to art. Key amongst these myths is the idea of art as a religion, according to which avant-garde artists are conceived as secular saints and martyrs. While this notion of artist as saint is strongly present in early-twentieth-century biographies of Van Gogh, Georges-Michel explicitly relates his fictionalized version of Modigliani’s life not to such recent models but rather to the Renaissance masters, and especially to Raphael, a link which is explained in terms of the post-war ‘retour à l’ordre’ in French artistic culture. The novel’s references to Raphael as archetypal painter-lover are also related to its construction of a myth of the artist as virile and sexually prolific, and to its identification of creative and sexual impulses

Synaptic Maturation at Cortical Projections to the Lateral Amygdala in a Mouse Model of Rett Syndrome

Rett syndrome (RTT) is a neuro-developmental disorder caused by loss of function of Mecp2 - methyl-CpG-binding protein 2 - an epigenetic factor controlling DNA transcription. In mice, removal of Mecp2 in the forebrain recapitulates most of behavioral deficits found in global Mecp2 deficient mice, including amygdala-related hyper-anxiety and lack of social interaction, pointing a role of Mecp2 in emotional learning. Yet very little is known about the establishment and maintenance of synaptic function in the adult amygdala and the role of Mecp2 in these processes. Here, we performed a longitudinal examination of synaptic properties at excitatory projections to principal cells of the lateral nucleus of the amygdala (LA) in Mecp2 mutant mice and their wild-type littermates. We first show that during animal life, Cortico-LA projections switch from a tonic to a phasic mode, whereas Thalamo-LA synapses are phasic at all ages. In parallel, we observed a specific elimination of Cortico-LA synapses and a decrease in their ability of generating presynaptic long term potentiation. In absence of Mecp2, both synaptic maturation and synaptic elimination were exaggerated albeit still specific to cortical projections. Surprisingly, associative LTP was unaffected at Mecp2 deficient synapses suggesting that synaptic maintenance rather than activity-dependent synaptic learning may be causal in RTT physiopathology. Finally, because the timing of synaptic evolution was preserved, we propose that some of the developmental effects of Mecp2 may be exerted within an endogenous program and restricted to synapses which maturate during animal life

Typologie des problèmes éthiques nommés par des employés du réseau québécois de la santé et des services sociaux à l’occasion de séances de groupes de codéveloppement professionnel

En matière d’éthique, les organisations optent le plus souvent pour une approche formaliste faisant appel au code d’éthique. L’approche formaliste omet toutefois de prendre en considération le sens que les acteurs d’une organisation donnent à ces normes. Afin de jeter les bases d’une éthique organisationnelle empirique partant du point de vue des acteurs, cette recherche propose une typologie des problèmes éthiques vécus en organisation à partir d’une analyse qualitative des verbatim de rencontres de groupes de codéveloppement professionnel dans le réseau québécois de la santé.When it comes to ethics, organizations most often opt for a formalistic approach using the code of ethics. The formalistic approach, however, fails to take into account the meaning that the actors of an organization give to these norms. In order to lay the foundations of an empirical organizational ethics based on the actors’ point of view, this research proposes a typology of the ethical problems experienced in organization through a qualitative analysis of the transcripts of professional co-development meetings held in the Quebec healthcare sector.En cuestiones de ética, las organizaciones optan generalmente por un enfoque formal recurriendo al código de ética. Sin embargo, el enfoque formal omite tener en cuenta el sentido que los actores de una organización dan a esas normas. Con el fin de sentar las bases de una ética organizacional empírica formulada por los actores, esta investigación propone una tipología de los problemas éticos de la organización a partir de un análisis cualitativo de las transcripciones de entrevistas con grupos de codesarrollo profesional en el sistema quebequense de la salud

Transitions in infant learning are modulated by dopamine in the amygdala

Behavioral transitions characterize development. Young infant rats paradoxically prefer odors that are paired with shock, but older pups learn aversions. This transition is amygdala and corticosterone dependent. Using microarrays and microdialysis, we found downregulated dopaminergic presynaptic function in the amygdala with preference learning. Corticosterone-injected 8-d-old pups and untreated 12-d-old pups learned aversions and had dopaminergic upregulation in the amygdala. Dopamine injection into the amygdala changed preferences to aversions, whereas dopamine antagonism reinstated preference learning

Structural connectomics of anxious arousal in early adolescence: Translating clinical and ethological findings

Etiological explanations of clinical anxiety can be advanced through understanding the neural mechanisms associated with anxiety in youth prior to the emergence of psychopathology. In this vein, the present study sought to investigate how trait anxiety is related to features of the structural connectome in early adolescence. 40 adolescents (21 female, mean age=13.49years) underwent a diffusion-weighted imaging scan. We hypothesized that the strength of several a priori defined structural connections would vary with anxious arousal based on previous work in human clinical neuroscience and adult rodent optogenetics. First, connection strength of caudate to rostral middle frontal gyrus was predicted to be anticorrelated with anxious arousal, predicated on extant work in clinically-diagnosed adolescents. Second, connection strength of amygdala to rostral anterior cingulate and to medial orbital frontal cortex would be positively and negatively correlated with anxious arousal, respectively, predicated on rodent optogenetics showing the former pathway is anxiogenic and the latter is anxiolytic. We also predicted that levels of anxiety would not vary with measures of global network topology, based on reported null findings. Results support that anxiety in early adolescence is associated with (1) the clinical biomarker connecting caudate to frontal cortex, and (2) the anxiogenic pathway connecting amygdala to rostral anterior cingulate, both in left but not right hemisphere. Findings support that in early adolescence, anxious arousal may be related to mechanisms that increase anxiogenesis, and not in a deficit in regulatory mechanisms that support anxiolysis. Keywords: Connectome, Anxiety, Adolescence, Translational neuroscience, Diffusion imagin