The overarching goal of this group is to develop techniques to optimize the functionality of the neural circuits that underlie behavior. Toward this end, we are primarily focused on an animal model that we have developed and studied over the last 5 years (Levine, Youngs et al. 2007; Levine, Leeder et al. 2008; Vitalo, Fricchione et al. 2009) . Using this model, we break down the broad question of how the brain shapes, and is shaped by, environmental changes, into three key questions. First, how do differential rearing conditions, both social and physical, impact neurological development and neuroplasticity at the cellular and physiological levels? Second, how do such changes in synaptic plasticity impact behavior and stress physiology? Third, can we develop interventions that reliably reproduce the behavioral and neuronal changes that occur in response to differential rearing conditions? This work is done in close collaboration with the Benson Henry Institute for Mind Body Medicine, Massachusetts General Hospital, where work performed in this laboratory can be translated to the clinical level in conjunction with their clinical research. In addition to the major focus on the interaction of environmental events and neuroplasticity, four other areas that this group has focused on in conjunction with other groups at the CEM and with other researchers at MGH are: 1) Fragile X Syndrome, the most common cause of inherited mental impairment; 2) the effect of adhesion molecules on the early differentiation of neural stem cells; 3) the use of a microfabricated slice culture for long term in vitro studies of synaptic connectivity; and 4) gene expression changes associated with fear extinction learning. Our current efforts are to elucidate key genetic, metabolic, and environmental pathways that affect synaptic plasticity in key regions of the brain involved in both cognitive and emotional learning and neurodevelopment. For these studies we employ a wide range of tools, including animal behavioral studies, basic molecular and cellular biological approaches, in-vivo (positron emission tomography) and ex-vivo (diffusion tensor imaging) approaches to whole brain imaging, tissue specific nuclear magnetic resonance selective control of gene expression in the central nervous system, sophisticated time lapse microscopy, and advanced BioMEMs devices.
Examples of ongoing projects include:
- Effect of differential sensory stimulation during rearing on behavior and wound healing
- Effect of rearing conditions and changes in neuronal function on peripheral stress hormones
- Functional brain imaging of brain changes during different rearing and physical stressors Identification of protein and gene expression changes in the hippocampus that regulate the HPA axis
- Effect of oxytocin on brain changes during differential rearing
- Vitalo A, Fricchione J, Rauch SL, Yarmush ML, Berthiaume F, Berdichevsky Y, Benson H, Fricchione G, Levine JB. Nest Building and Oxytocin Comparably Improve Wound Healing in Isolation Reared Rats, PLoS One 2009; 4: e5523.
- Berdichevsky Y, Sabolek H, Levine JB, Staley KJ, Yarmush ML. Microfluidics and multielectrode array-compatible organotypic slice culture method, Journal of Neuroscience Methods 2009; 178: 59-64.
- Levine JB, Leeder AD, Parekkadan B, Berdichevsky Y, Rauch, SL, Smoller JW, Konradi, C, Berthiaume, F, Yarmush, ML Isolation Rearing Impairs Wound Healing and is Associated with Increased Locomotion and Decreased Immediate Early Gene Expression in the Medial Prefrontal Cortex of Juvenile Rats. Neuroscience 2008, 151: 589-603.
- Parekkadan B, Berdichevsky Y, Irimia D, Leeder A, Toner M, Levine, JB, Yarmush, ML, Cell- cell interaction modulates neuroectodermal specification of embryonic stem cells, Neuroscience Letters 2008; 438: 190-195.
- Levine JB, Youngs RM, MacDonald MS, Chu, M, Leeder AD, Berthiaume F, Konradi, C. Isolation Rearing and Hyperlocomotion are Associated with Reduced Immediate Early Genes Expression Levels in the Medial Prefrontal Cortex. Neuroscience 2007, 145: 42-55.
- Rosenblatt LE, Gorantla S, Torres, JA, Yarmush RS, Rao S, Park ER, Denninger JW, Benson H, Fricchione GL, Bernstein B, Levine, JB. Relaxation Response Based Yoga Improves Functioning in Young Children with Autism: A Pilot Study. Journal of Alternative and Complementary Medicine, in press
- Stoddard, FJ; Levine JB, Lund KK. “Burn Injuries”, in Psychosomatic Medicine, Blumenthal, M and Strain, JJ; Lippincott, Williams & Wilkins, 2006.
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