Bruce Thomas Hope, Ph.D.
Behavioral Neuroscience Research Branch, Neuronal Ensembles in Drug Addiction
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.
- Madangopal R, Ramsey LA, Weber SJ, Brenner MB, Lennon VA, Drake OR, Komer LE, Tunstall BJ, Bossert JM, Shaham Y, Hope BT. Inactivation of the infralimbic cortex decreases discriminative stimulus-controlled relapse to cocaine seeking in rats. Neuropsychopharmacology. 2021;46(11):1969-1980.
- Whitaker LR, Warren BL, Venniro M, Harte TC, McPherson KB, Beidel J, Bossert JM, Shaham Y, Bonci A, Hope BT. Bidirectional Modulation of Intrinsic Excitability in Rat Prelimbic Cortex Neuronal Ensembles and Non-Ensembles after Operant Learning. J Neurosci. 2017;37(36):8845-8856.
- Warren BL, Kane L, Venniro M, Selvam P, Quintana-Feliciano R, Mendoza MP, Madangopal R, Komer L, Whitaker LR, Rubio FJ, Bossert JM, Caprioli D, Shaham Y, Hope BT. Separate vmPFC Ensembles Control Cocaine Self-Administration Versus Extinction in Rats. J Neurosci. 2019;39(37):7394-7407.
- Rubio FJ, Olivares DE, Dunn C, Zhang S, Hilaire EM, Henry A, Mejias-Aponte C, Nogueras-Ortiz CJ, Selvam PV, Cruz FC, Madangopal R, Morales M, Hope BT. Flow Cytometry of Synaptoneurosomes (FCS) Reveals Increased Ribosomal S6 and Calcineurin Proteins in Activated Medial Prefrontal Cortex to Nucleus Accumbens Synapses. J Neurosci. 2023;43(23):4217-4233.
- Cruz FC, Koya E, Guez-Barber DH, Bossert JM, Lupica CR, Shaham Y, Hope BT. New technologies for examining the role of neuronal ensembles in drug addiction and fear. Nat Rev Neurosci. 2013;14(11):743-54.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
Biomedical Engineering and Biophysics
This page was last updated on Thursday, August 24, 2023