PRINCIPAL INVESTIGATORS

CONTACT ME

Bruce Thomas Hope, Ph.D., Investigator

Chief, Neuronal Ensembles in Drug Addiction

Post-doctoral Training – Laboratory of Molecular Psychiatry, Department of Psychiatry, Yale University (advisor: Dr. Eric Nestler)

Ph.D. – Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, Canada (thesis advisor: Dr. Steven R. Vincent)

B.Sc. – Biochemistry, University of British Columbia, Vancouver, Canada

RESEARCH INTERESTS

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.

Selected Publications:

1. Guez-Barber DH, Fanous S, Harvey BK, Zhang Y, Becker KG, Picciotto MR, Hope BT. (2012) FACS purification of immunolabeled cell types in adult rat brain. J. Neurosci. Meth. 203:10-18.

2. Koya E, Golden SA, Hoffman AF, Lupica CR, Hope BT. Synaptic remodeling in nucleus accumbens neurons recruited during cocaine sensitization. (invited resubmission to Nat. Neurosci.)

3. Bossert JM, Stern AL, Theberge FRM, Cifani C, Koya E, Hope BT, Shaham Y. (2011) Ventral medial prefrontal cortex neuronal ensembles mediate context-induced relapse to heroin. Nat Neurosci. 14:420-422.

4. Guez-Barber DH, Harvey BK, Becker KG, Picciotto MR, Hope BT. (2011) FACS identifies unique cocaine-induced gene regulation in selectively activated adult striatal neurons. J. Neurosci. 31:4251-4259.

5. Marin M, Berkow A, Golden S, Koya E, Planeta, C, Hope BT. (2009) Context-specific modulation of signal transduction in rat nucleus accumbens following cocaine sensitization. Eur. J. Neurosci. 30:1931-1940.

6. Koya E, Golden SA, Berkow A, Simmons DE, Bossert JM, Nair SG, Uejima JL, Marin MT, Mitchell TB, Farquhar D, Ghosh S, Mattson BJ, Hope BT. (2009) Targeted disruption of cocaine-activated accumbens neurons prevents context-specific sensitization Nat Neurosci.12:1069-1073.

7. Mattson BJ, Koya E, Simmons DE, Mitchell TB, Berkow A, Crombag HS, Hope BT. (2008) Context-specific sensitization and associated neuronal ensembles in rat nucleus accumbens. Eur. J. Neurosci. 27:202-212.

8. Hope BT, Simmons DE, Mitchell T, Kreuter JD, Mattson BJ. (2006) Cocaine-induced locomotor activity and Fos expression in nucleus accumbens is sensitized for 6 months after repeated cocaine administration in a novel environment. Eur. J. Neurosci. 24:867-875.

9. Morón JA, Brockington A, Wise R, Rocha BA, Hope BT (2002) Dopamine uptake through the NET in brain regions with low levels of the DAT: Evidence from knockout mouse lines. J. Neurosci. 22(2):389-395.

10. Hope BT, Nye HE, Kelz MB, Self DS, Iadarola MJ, Nakabeppu Y, Duman RS, Nestler EJ. (1994) Induction of a long-lasting AP-1 complex composed of novel Fos-like proteins in brain: Effects of chronic cocaine and other chronic treatments. Neuron 13:1235-44.

About Dr. Hope's...

IRP Training Opportunities...