Prof. Seth Blackshaw
Department of Neuroscience Johns Hopkins University School of Medicine Baltimore
Lecture topic: Radial glia in health and disease
Rosenberg Building, Hall 01
Past seminar at Sagol School of Neuroscience: 03.05.2015
Projects in the lab include:
Past seminar at Sagol School of Neuroscience: 8.12.16
Lecture title: Neuronal ensembles in operant learned responding for food and drug rewards
When using drugs of abuse, learned associations are formed between the drugs and stimuli present in the drug-taking environment. With continued use, these stimuli can become cues that promote drug relapse. Our research is focused on figuring out how these memories are stored in the brain. We have identified sparsely distributed patterns of neurons in the brain called ‘neuronal ensembles’ that are selectively activated by drug-related cues and thought to encode the learned associations that mediate drug seeking behavior. Drug-related cues activate specific genes such as c-fos within these neuronal ensembles and allow us to identify them in the brain. We exploit the c-fos promoter to turn on different transgenes in transgenic rats that allow us to manipulate specific neuronal ensembles and assess their role in drug-related memories. We also developed a fluorescence-activated cell sorting (FACS) procedure for purifying these activated ensembles and found unique molecular alterations within their cell bodies and synapses. We have developed novel c-fos-GFP transgenic rats that produce green fluorescent protein (GFP) in activated neurons and found unique synaptic alterations using slice electrophysiology. Using a combination of novel viruses and transgenic rats developed in collaboration with Dr. Brandon Harvey, we continue to search and characterize drug-related memory engrams in the brain that promote drug relapse.
Synaptic transmission underlies every aspect of nervous system function. How we think, feel, act and learn, all rely on information transfer between nerve cells. In addition, synapses are extremely dynamic, and activity-dependent changes in synaptic strength are essential to most forms of learning. It is becoming increasingly clear that synaptic dysfunction is central to the etiology and progression of a wide range of neuropsychiatric and neurodevelopmental disorders. The main goal of my research program is to understand the cellular and molecular basis of activity-dependent changes in synaptic strength at both excitatory and inhibitory connections, and how such changes are modified during pathological conditions. In our studies we use brain slice electrophysiology and pharmacology, two-photon laser microscopy, optogenetics and a wide-range of molecular manipulations. To gain insights into the mechanisms of synaptic function, we include in our studies functional analyses of transgenic mice for several synaptic proteins, as well as mouse models for various neuropsychiatric conditions, including Alzheimer’s disease, autistic spectrum disorders and schizophrenia.