The Neuroscience Program at The Saban Research Institute

Neuroscience Research Video length: 07:23

Quicklinks Research Focus Accomplishments Members Institute for the Developing Mind

Director:  Richard B. Simerly, PhD

How the brain functions depends on the organization of complex arrays of neuronal circuits that are established during development. We now know that a variety of neurological and psychiatric diseases have their origins in development, but we need to learn more about how the brain develops in order to identify effective therapies.

Our program is focused on understanding basic developmental neurobiological events by using a combined molecular genetic and cellular imaging approach. Combining with in vivo imaging studies, this approach promises to provide novel machanistic insights into the developmental origins of such devastating disorders as autism, fragile X syndrome and juvenile obesity. By focusing on key developmental critical periods and incorporating insight gainged from clinical observation, the scientists of the Neuroscience Program work to understand the relationship between abnormal brain development and disease.

Our goal is to exploit the inherent plasticity of the neonatal central nervous system to rescue normal function of affected brain circuitry and restore the full range of learning and experience that are essential components of childhood.

Clinical Research

Cellular mechanisms underlying development of forebrain circuits controlling metabolism and associated behaviors.

Laboratory Research
The major focus of the laboratory is to determine how endocrine signals direct formation of limbic-hypothalamic neural circuitry involved in the regulation of homeostatis. The hypothalmus is uniquely situated to control a wide variety of organ systems, while at the same time responding to endocrine feedback signals sent from those organs. Remarkably, the same hormonal signals that communicate to the hypothalamus in mature animals can impact formation of hypothalamic neural pathways during development so as to permanently alter their functional activity.

Currently, we are studying the development of forebrain pathways that regulate feeding and energy metabolism. Recent findings indicate that the fat cell derived hormone leptin acts on the hypothalamus during a discrete critical period of postnatal development to govern the assembly of homeostatic circuits known to control body weight and glucose development to govern the assembly of homeostatic circuits known to control body weight and gluclose metabolism. For this work, we use cellular imaging methods and computer assisted visualization tools, together with genetically manipulated animal models, to study how specific genes mediate the construction of hypothalamic neural networks.

The results of this work indicate that leptin is a major developmental factor that acts directly on the neonatal brain to specify patterns of connectivity in response to a variety of environmental factors including nutrition. The long term goal of this research is to harness the regulatory power of endocrine signals to program the developing brain for lasting health and an optimized metabolic phenotype.

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