1,106 research outputs found

    NMDAR-Mediated Calcium Transients Elicited by Glutamate Co-Release at Developing Inhibitory Synapses

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    Before hearing onset, the topographic organization of the inhibitory sound localization pathway from the medial nucleus of the trapezoid body (MNTB) to the lateral superior olive (LSO) is refined by means of synaptic silencing and strengthening. During this refinement period MNTB-LSO synapses not only release GABA and glycine but also release glutamate. This co-released glutamate can elicit postsynaptic currents that are predominantly mediated by NMDA receptors (NMDARs). To gain a better understanding of how glutamate contributes to synaptic signaling at developing MNTB-LSO inhibitory synapses, we investigated to what degree and under what conditions NMDARs contribute to postsynaptic calcium responses. Our results demonstrate that MNTB-LSO synapses can elicit compartmentalized calcium responses along aspiny LSO dendrites. These responses are significantly attenuated by the NMDAR antagonist APV. APV, however, had no effect on somatically recorded electrical postsynaptic responses, indicating little, if any, contribution of NMDARs to spike generation. NMDAR-mediated calcium responses were decreased when increasing extracellular magnesium concentrations to physiological levels indicating that MNTB-LSO synapses activate magnesium sensitive NMDAR on immature LSO dendrites. In Fura-2 AM loaded neurons, blocking GABAA and glycine receptors increased NMDAR contribution to somatic calcium responses suggesting that GABA and glycine, perhaps by shunting backpropagating action potentials, decrease the level of NMDAR activation under strong stimulus conditions

    A study in the elements of rapport

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    Thesis (M.S.)--Boston University, 1950. This item was digitized by the Internet Archive

    Mice Lacking the Alpha9 Subunit of the Nicotinic Acetylcholine Receptor Exhibit Deficits in Frequency Difference Limens and Sound Localization

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    Sound processing in the cochlea is modulated by cholinergic efferent axons arising from medial olivocochlear neurons in the brainstem. These axons contact outer hair cells in the mature cochlea and inner hair cells during development and activate nicotinic acetylcholine receptors composed of α9 and α10 subunits. The α9 subunit is necessary for mediating the effects of acetylcholine on hair cells as genetic deletion of the α9 subunit results in functional cholinergic de-efferentation of the cochlea. Cholinergic modulation of spontaneous cochlear activity before hearing onset is important for the maturation of central auditory circuits. In α9KO mice, the developmental refinement of inhibitory afferents to the lateral superior olive is disturbed, resulting in decreased tonotopic organization of this sound localization nucleus. In this study, we used behavioral tests to investigate whether the circuit anomalies in α9KO mice correlate with sound localization or sound frequency processing. Using a conditioned lick suppression task to measure sound localization, we found that three out of four α9KO mice showed impaired minimum audible angles. Using a prepulse inhibition of the acoustic startle response paradigm, we found that the ability of α9KO mice to detect sound frequency changes was impaired, whereas their ability to detect sound intensity changes was not. These results demonstrate that cholinergic, nicotinic α9 subunit mediated transmission in the developing cochlear plays an important role in the maturation of hearing

    Ten simple rules for principled simulation modelling

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    The Genetic Foundations of Attitude Formation: The Case of Left-Right Political Orientations

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    Kandler C, Bell E, Shikishima C, Yamagata S, Riemann R. The Genetic Foundations of Attitude Formation: The Case of Left-Right Political Orientations. In: R. A. S, S. M. K, eds. Emerging Trends in the Social and Behavioral Sciences: Interdisciplinary Directions. In Press.Since the pioneering work of Eaves and Eysenck (1974) appeared in Nature some 40 years ago,psychologists, sociologists, political scientists, and behavioral geneticists have investigated the effects of nature and nurture on the formation of social attitudes. It has consistently been found that manifestations of social attitudes (i.e., preferences, values, and beliefs pertaining to things like politics, religion, the treatment of ingroups and outgroups, etc.) are genetically influenced. More recently, researchers have focused their efforts on the psycho-physiological pathways between gene activity and attitudes. In particular, a broad body of research examines how personality traits may be a link between genetic factors and political orientations. The latter are typically treated as either a single left-right dimension or divided into two core aspects: resistance to change/authoritarian conservatism and acceptance of inequality/social dominance orientation. In this article, we provide an overview of this research, present some findings from our recent international behavioral genetic study on the topic, and identify key issues for future research. We suggest that future studies treat attitude formation as a complex process in which genetic factors and the psycho-physiological phenomena that stem from them are affected by the surrounding social environment and culture. Such research will require: (1) international study designs capturing individual and cultural levels of variation; and: (2) interdisciplinary collaboration among scientists and researchers in various fields of study such as genetics, psychology, sociology, political science, neuroscience, and human biology

    Cyclic Photophosphorylation in Vivo

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