E. David Leonardo, MD, PhD
Our primary interest is in understanding how temporal factors, genetic risk, and environmental milieu interact to impact on the expression of mental illness. As the brain develops, distinct neural circuits develop within narrowly defined time periods. These precisely defined time windows provide the opportunity for short-lived gene X environment interactions that ultimately determine the functioning of mature circuitry and the behaviors that they mediate. In a longstanding collaboration with Alex Dranovsky, we are examining the effects of stressful and enriching experiences on mature and immature brain circuitry in the mouse, with the aim of understanding how such effects produce alterations in behavior.
In another area of investigation, we use novel, regulatable, serotonin-1A receptor mutant mice to disrupt normal serotonergic signaling in early development. Using this system, we can independently manipulate either specific cortical 5-HT1A medicated signaling by selectively removing cortical receptors, or globally disrupt serotonergic signaling by removing 5-HT1A receptors in the raphe, which provide negative feedback for serotonergic neurons. Using this model system, we have already identified distinct effects of cortical receptors on depression related behavior and raphe receptors on anxiety related behavior. We are currently investigating the time course during which the distinct circuits mediating these behaviors are vulnerable to disruption.
- 1999 University of California San Francisco School of Medicine
- Internship: 2001 New York State Psychiatric Institute
- Residency: 2003 NewYork-Presbyterian Hospital/Columbia University Medical Center
- Garcia-Garcia, A.L., Meng, Q., Canetta, S., Gardier, A.M., Guiard, B.P., Kellendonk, C., Dranovsky, A., *Leonardo, E.D. Serotonin signaling through Prefrontal Cortex 5-HT1A receptors during adolescence can determine baseline mood-related behaviors. (2017) Cell Reports. Jan 31;18(5) 1144-1156.
- Garcia-Garcia, A.L., Meng, Q., Richardson-Jones, J., Dranovsky, A., Leonardo, E.D. (2015) Disruption of 5-HT1A function in adolescence but not early adulthood leads to sustained increases of anxiety. doi:10.1016/j.neuroscience.2015.05.076.
- Kirshenbaum GS, Lieberman SR, Briner TJ, Leonardo ED, Dranovsky A. (2014) Adolescent but not adult-born neurons are critical for susceptibility to chronic social defeat. Front Behav Neurosci. 8:289.
- Richardson-Jones JW1, Craige CP, Guiard BP, Stephen A, Metzger KL, Kung HF, Gardier AM, Dranovsky A, David DJ, Beck SG, Hen R, Leonardo ED. (2010) 5-HT1A autoreceptor levels determine vulnerability to stress and response to antidepressants. Neuron. 65:40-52. doi: 10.1016/j.neuron.2009.12.003.
- Leonardo, E.D. (2010). 5-HT1A autoreceptors determine vulnerability to stress and response to antidepressants. Neuron 65: 40-52.
- Leonardo, E. D., and Hen, R. (2007) Anxiety as a Developmental Disorder. Neuropsychopharmacology reviews 2007: 1: 1-7.
- Mood Disorder