Selected references
PhD 1995, Yale University. Postdoctoral research at Columbia University.
Cornelius Gross
Group leader at EMBL Monterotondo since 2003. Audero, E., Coppi, E., Mlinar, B., Rossetti, T., Caprioli, A. et al. (2008). Sporadic autonomic dysregulation and death associated with excessive serotonin autoinhibition. Science, 321, 130-133
Senior scientist since 2009.
Lo Iacono, L. & Gross, C. (2008). AlphaCa2+/calmodulindependent protein kinase II contributes to the developmental programming of anxiety in serotonin receptor 1A knock-out mice. J. Neurosci., 28, 6250-6257
Previous and current research
Carola, V., Frazzetto, G., Pascucci, T., Audero, E., Puglisi-Allegra, S. et al. (2008). Identifying molecular substrates in a mouse model of the serotonin transporter x environment risk factor for anxiety and depression. Biol. Psychiatry, 63, 840-846 Tsetsenis, T., Ma, X.H., Lo Iacono, L., Beck, S.G. & Gross, C. (2007). Suppression of conditioning to ambiguous cues by pharmacogenetic inhibition of the dentate gyrus. Nat Neurosci., 10, 896-902
Developmental programming of anxiety Anxiety disorders are debilitating mental illnesses characterised by excessive worry and rumination and exaggerated responses to threatening stimuli. Epidemiological studies suggest that both genetic and environmental factors contribute to the prevalence of these disorders. For example, exposure to adverse events such as trauma, maltreatment, or negligence during childhood is known to result in an increased risk of anxiety disorders in adulthood. However, not all persons subjected to such events develop anxiety, and genetic factors are thought to influence the long-term outcome of such experiences. Recently a number of specific genetic polymorphisms have been identified that moderate susceptibility to mental illness following exposure to childhood adversity. However, we know little about the neural circuits and molecular substrates that underlie such gene-by-environment risk factors. A better understanding of the molecular mechanisms involved could lead to novel diagnostic and therapeutic approaches for mental illness in humans. We are using pharmacological, histochemical, electrophysiological and behavioural genetic approaches to study the neural circuits underlying anxiety behaviour in mice. Several ongoing projects in the lab are addressing this question from different angles. Early gene-by-environment risk factors: We are particularly interested in understanding how exposure to early adverse experiences can program anxiety behaviour in adulthood. We have shown that exposure to low levels of maternal care is associated with increased anxiety and depression-related behaviour in adulthood and that this effect is moderated by specific mutations in genes that are known to play a role in brain development and plasticity. We are using tissue-specific and temporally controlled gene expression technology in transgenic mice to identify the neural circuits and critical time periods for these effects. We are also examining changes in gene expression and epigenetic marks associated with altered early environmental exposure. Finally, we are collaborating with psychiatrists to examine whether gene-by-environment risk factors identified in the mouse are also predisposing factors for behavioural disorders in human. Cellular substrates of anxiety: To help identify the cellular substrates of anxiety, we are using pharmacogenetic transgenic tools for the rapid modulation of electrical activity in selected cell-types in the brain. We have used a pharmaco-genetic inhibition strategy to examine the contributions of hippocampal and amygdala cell-types to anxiety and fear behavior. We are further developing these tools and combining them with electrophysiological recordings in awake behaving mice to identify the cell-types and circuits involved.
Future projects and goals •
Identification of molecular mechanisms that mediate the long-term programming of behaviour by early environmental experiences in mice and humans (genetic, epigenetic, hormonal, electrophysiological, morphological, and signaling mechanisms);
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creation of mouse models of specific human genetic variations that have been associated with behavioural disorders;
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development and application of pharmaco-genetic transgenic technologies for the tissue and celltype specific suppression of neural activity in behaving mice;
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identification and validation of the neurophysiological correlates of anxiety in behaving mice;
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study of copy number variations as predisposing factors for disease in mice.
Together these approaches are aimed at discovering the long-term plastic mechanisms that underlie susceptibility to anxiety. A better understanding of the molecular signals that trigger these plastic changes will allow us to form specific hypotheses about how human anxiety is determined and may lead to improved diagnostic and therapeutic tools in the clinic.
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