Journal ArticleDOI
Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult.
Cornelius Gross,Xiaoxi Zhuang,Xiaoxi Zhuang,Kimberly L. Stark,Sylvie Ramboz,Ronald Oosting,Lynn G. Kirby,Luca Santarelli,Sheryl G. Beck,René Hen +9 more
TLDR
Findings show that postnatal developmental processes help to establish adult anxiety-like behaviour, and the normal role of the serotonin1A receptor during development may be different from its function when this receptor is activated by therapeutic intervention in adulthood.Abstract:
Serotonin is implicated in mood regulation, and drugs acting via the serotonergic system are effective in treating anxiety and depression. Specifically, agonists of the serotonin1A receptor have anxiolytic properties, and knockout mice lacking this receptor show increased anxiety-like behaviour. Here we use a tissue-specific, conditional rescue strategy to show that expression of the serotonin1A receptor primarily in the hippocampus and cortex, but not in the raphe nuclei, is sufficient to rescue the behavioural phenotype of the knockout mice. Furthermore, using the conditional nature of these transgenic mice, we suggest that receptor expression during the early postnatal period, but not in the adult, is necessary for this behavioural rescue. These findings show that postnatal developmental processes help to establish adult anxiety-like behaviour. In addition, the normal role of the serotonin1A receptor during development may be different from its function when this receptor is activated by therapeutic intervention in adulthood.read more
Citations
More filters
Journal ArticleDOI
Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants
Luca Santarelli,Michael Saxe,Cornelius Gross,Alexandre Surget,Fortunato Battaglia,Stephanie C. Dulawa,Noelia V. Weisstaub,James T. Lee,Ronald S. Duman,Ottavio Arancio,Catherine Belzung,René Hen +11 more
TL;DR: It is shown that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants, suggesting that the behavioral effects of chronic antidepressants may be mediated by the stimulation of neuroGenesis in the hippocampus.
Journal ArticleDOI
Serotonin Transporter Genetic Variation and the Response of the Human Amygdala
Ahmad R. Hariri,Venkata S. Mattay,Alessandro Tessitore,Bhaskar Kolachana,Francesco Fera,David Goldman,Michael F. Egan,Daniel R. Weinberger +7 more
TL;DR: Genetically driven variation in the response of brain regions underlying human emotional behavior is demonstrated and differential excitability of the amygdala to emotional stimuli may contribute to the increased fear and anxiety typically associated with the short SLC6A4 allele.
Journal ArticleDOI
Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression
TL;DR: Because the MPFC and related limbic structures provide forebrain modulation over visceral control structures in the hypothalamus and brainstem, their dysfunction can account for the disturbances in autonomic regulation and neuroendocrine responses that are associated with mood disorders.
Journal ArticleDOI
Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease
Jong-Hoon Kim,Jonathan M. Auerbach,José A. Rodríguez-Gómez,Iván Velasco,Denise K. Gavin,Nadya Lumelsky,Sang-Hun Lee,John Bang Nguyen,Rosario Sanchez-Pernaute,Krys S. Bankiewicz,Ronald D.G. McKay +10 more
TL;DR: It is shown that a highly enriched population of midbrain neural stem cells can be derived from mouse ES cells and the dopamine neurons generated by these stem cells show electrophysiological and behavioural properties expected of neurons from the midbrain.
Journal ArticleDOI
Psychobiological Mechanisms of Resilience and Vulnerability: Implications for Successful Adaptation to Extreme Stress
TL;DR: An integrative model of resilience and vulnerability that encompasses the neurochemical response patterns to acute stress and the neural mechanisms mediating reward, fear conditioning and extinction, and social behavior is proposed.
References
More filters
Journal ArticleDOI
Control of memory formation through regulated expression of a CaMKII transgene
TL;DR: A forebrain-specific promoter was combined with the tetracycline transactivator system to achieve both regional and temporal control of transgene expression, and the CaMKII signaling pathway is critical for both explicit and implicit memory storage.
Journal ArticleDOI
Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat
Christian Caldji,Beth Tannenbaum,Shakti Sharma,Darlene D. Francis,Paul M. Plotsky,Michael J. Meaney +5 more
TL;DR: It is suggested that maternal care during infancy serves to "program" behavioral responses to stress in the offspring by altering the development of the neural systems that mediate fearfulness.
Journal ArticleDOI
Serotonin receptor 1A knockout: an animal model of anxiety-related disorder.
Sylvie Ramboz,Ronald S. Oosting,Djamel Ait Amara,Hank F. Kung,Pierre Blier,Monica Mendelsohn,J. John Mann,Dani Brunner,René Hen +8 more
TL;DR: It is demonstrated that mice without 5-HT1A receptors display decreased exploratory activity and increased fear of aversive environments (open or elevated spaces) and suggested that reductions in 5- HT1A receptor density due to genetic defects or environmental stressors might result in heightened anxiety.
Journal ArticleDOI
Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice.
Andreas Kistner,Manfred Gossen,Frank Zimmermann,Jasna Jerecic,Christoph Ullmer,Hermann Lübbert,Hermann Bujard +6 more
TL;DR: Both tetracycline-controlled transcriptional activation systems provide genetic switches that permit the quantitative control of gene activities in transgenic mice in a tissue-specific manner and, thus, suggest possibilities for the generation of a novel type of conditional mutants.
Journal ArticleDOI
G Protein-Coupled Inwardly Rectifying K+ Channels (GIRKs) Mediate Postsynaptic but Not Presynaptic Transmitter Actions in Hippocampal Neurons
TL;DR: It is suggested that a number of G protein-coupled receptors activate the same class of postsynaptic K+ channel, which contains GIRK2, and that the same receptor can couple to different effector systems according to its subcellular location in the neuron.