Source: Interfolio F180
Marisa Roberto
Scripps Research Joint Appointments
Research Focus
Neuronal Functions and Synaptic Communication: Neuropeptides and Drugs of Abuse
Alcoholism is a chronic relapsing illness that accounts for major disability worldwide and available treatments are insufficient. Current and future studies in my laboratory aim to understand the specific neuronal mechanisms that underlie synaptic and/or molecular changes to influence the development of dependence to alcohol and other drugs of abuse (nicotine, cocaine etc.). Tolerance occurs through adaptations at the cellular level, as the brain attempts to overcome the acute effects of drugs of abuse. With prolonged drug use, these adaptations often lead to significant changes in the structure and function of neurons. The synapse is the primary point for information transfer between neurons, and a central hypothesis is that synapses are the most sensitive sites of action for drugs of abuse. We primarily study the synapses of the central nucleus of the amygdala (CeA), a brain region that plays a central role in the behavioral effects of acute and chronic drug consumption, and in the physiological responses to fearful stimuli and stressful stimuli.
The aim of my group is to understand the effects of drugs of abuse on neuronal function and synaptic transmission using electrophysiological, pharmacological, and molecular methods. We have characterized several neuroadaptative changes that provide seminal insights into synaptic transmission and that will be useful towards developing new therapeutic agents to alleviate drug dependence, and particularly alcohol dependence. In parallel, our studies identified key functional roles for neuropeptide neurotransmitters in the neurocircuits that mediate motivated behavior.
Our early studies significantly advanced the field of alcohol research by elucidating critical synaptic and molecular mechanisms regarding the unique sensitivity of the G-aminobutyric acid (GABA) and glutamatergic systems in CeA to acute and chronic ethanol. We found that an anti-epileptic drug gabapentin (a structural analogue of GABA) reverses several behavioral aspects of ethanol dependence. These behavioral and cellular findings with gabapentin suggest the potential for use as a possible medication for the treatment of alcoholism. A fundamental dichotomy exists between systems that mediate positively reinforced alcohol consumption ('reward drinking') versus negatively reinforced intake ('relief drinking'). Over time, chronic elevated alcohol consumption results in neuroadaptations that involve the recruitment and pathological activity of extrahypothalamic stress systems, providing an incentive for negatively reinforced alcohol intake. The neuropeptide corticotropin-releasing factor (CRF) in the CeA has been hypothesized to have an important role in brain emotional function. We have characterized synaptic action of CRF in CeA and the involvement of this system and other stress-related neurotransmitters/neuroregulators (e.g.; nociceptin and neuropeptide Y) in alcohol dependence. We are also examining the actions of other neuromessenger systems, such as those for PACAP, endocannabinoids and opioids, on CeA synaptic transmission, and how these systems are affected by alcohol dependence and stress. The characterization of the amygdala neurocircuitry and connections with other brain regions (e.g. ventral tegmental area, prefrontal cortex, the bed nucleus of stria terminalis) as well as neuroinflammation are new areas of interest of my lab. Our findings provide a framework for further molecular and cellular research that will facilitate medication development and may help tailor personalized therapies for alcoholism and other addictive disorders.
Education
Ph.D. (Biology), University of Pisa, 2001B.A. (Biology), University of Pisa, 1996
Awards & Professional Activities
1996 University Enterprises Training Partnership (EUTP) Fellowship, The Brabraham Institute of Cambridge (UK)2005 Young Investigator Award, Research Society on Alcoholism
2005 Researcher at the Pearson Center for Alcoholism and Addiction Research
2005 Faculty Member of the Helen Dorris Neurological Research Center, MIND, TSRI
2006 Invited Plenary Speaker, Research Society on Alcoholism
2007 Young Investigator Award, ESBRA
2007 Member of the Fundraising Committee, Research Society on Alcoholism
2008 Organizer of the Triennial International Meeting: Alcoholism and Stress: A Framework for Future Treatment Strategies
2008 Member of the RSA Research Priorities Committee, Research Society on Alcoholism
2009 Presidential Early Career Awards for Scientists and Engineers (PECASE), President Barack Obama, USA
2011 Knight of the "Order of Merit of the Republic of Italy", Republic of Italy
2012 TSRI Faculty Lecture Series "Alcohol dependence: synaptic neuroadaptations in the amygdala", The Scripps Research Institute
2012 Congress Travel Award, ISBRA
2013 The 6th Edition of the International Prize "Genoa: a woman standing out from the crowd"
2016 The Jacob P. Waletzky Award, Society for Neuroscience
Selected Publications
Kreifeldt, M.; Herman, M. A.; Sidhu, H.; Okhuarobo, A.; Macedo, G. C.; Shahryari, R.; Gandhi, P. J.; Roberto, M.; Contet, C. Central amygdala corticotropin-releasing factor neurons promote hyponeophagia but do not control alcohol drinking in mice.. Molecular Psychiatry 2022, 27, 2502-2513.
[View]
Varodayan, F. P.; de Guglielmo, G.; Logrip, M. L.; George, O.; Roberto, M. Alcohol dependence disrupts amygdalar L-type voltage-gated calcium channel mechanisms. Journal of Neuroscience 2017, 37, 4593-4603.
[View]
Bajo, M.; Herman, M. A.; Varodayan, F. P.; Oleata, C. S.; Madamba, S. G.; Harris, R. A.; Blednov, Y. A.; Roberto, M. Role of the IL-1 receptor antagonist in ethanol-induced regulation of GABAergic transmission in the central amygdala. Brain Behavior and Immunity 2015, 45, 189-197.
[View]
Roberto, M.; Contet, C.; Woodward, J. J.; Roberto, M.; Contet, C.; Woodward, J. J.; Trenet, W.; Sibley, B. D.; Roberto, M.; Purohit, D. C.; Osorno, R. E.; Oliver, R. J.; Mandyam, C. D.; Contet, C.; Avchalumov, Y. Chronic ethanol exposure differentially alters neuronal function in the medial prefrontal cortex and dentate gyrus.. Neuropharmacology 2021, 185, 108438.
[View]
Spierling, S. R.; de Guglielmo, G.; Kirson, D.; Kreisler, A.; Roberto, M.; George, O.; Zorrilla, E. P. Insula to ventral striatal projections mediate compulsive eating produced by intermittent access to palatable food. Neuropsychopharmacology 2020, 45, 579-588.
[View]
Harris, R. A.; Bajo, M.; Bell, R. L.; Blednov, Y. A.; Varodayan, F. P.; Truitt, J. M.; Lasek, A. W.; Logrip, M. L.; Vendruscolo, L. F.; Roberts, A. J.; Roberts, E.; Roberts, E.; George, O.; Mayfield, J.; Billiar, T. R.; Hackam, D. J.; Mayfield, R. D.; Koob, G. F.; Koob, G. F.; Roberto, M.; Roberto, M.; Homanics, G. E.; Roberts, E.; Roberto, M.; Koob, G. F.; Guglielmo, G. D. Genetic and Pharmacologic Manipulation of TLR4 Has Minimal Impact on Ethanol Consumption in Rodents. The Journal of neuroscience : the official journal of the Society for Neuroscience 2017, 37, 1139-1155.
[View]
Grieder, T. E.; Herman, M. A.; Contet, C.; Tan, L. A.; Vargas-perez, H.; Cohen, A.; Chwalek, M.; Maal-bared, G.; Freiling, J.; Schlosburg, J. E.; Clarke, L.; Crawford, E.; Koebel, P.; Repunte-canonigo, V.; Sanna, P. P.; Tapper, A. R.; Roberto, M.; Kieffer, B. L.; Sawchenko, P. E.; Koob, G. F.; George, O.; Kooy, D. V. VTA CRF neurons mediate the aversive effects of nicotine withdrawal and promote intake escalation.. Nature neuroscience 2014, 1751-8.
[View]
Ciccocioppo, R.; de Guglielmo, G.; Hansson, A. C.; Ubaldi, M.; Kallupi, M.; Cruz, M. T.; Oleata, C. S.; Heilig, M.; Roberto, M. Restraint stress alters nociceptin/orphanin FQ and CRF systems in the rat central amygdala: significance for anxiety-like behaviors. Journal of Neuroscience 2014, 34, 363-372.
[View]
Bajo, M.; Cruz, M. T.; Siggins, G. R.; Messing, R.; Roberto, M. Protein kinase C epsilon mediation of CRF- and ethanol-induced GABA release in central amygdala. Proceedings of the National Academy of Sciences of the United States of America 2008, 105, 8410-8415.
[View]
Herman, M. A.; Roberto, M. Cell-type-specific tonic GABA signaling in the rat central amygdala is selectively altered by acute and chronic ethanol. Addiction Biology 2016, 21, 72-86.
[View]
Cottone, P.; Sabino, V.; Roberto, M.; Bajo, M.; Pockros, L.; Frihauf, J. B.; Fekete, E. M.; Steardo, L.; Rice, K. C.; Grigoriadis, D. E.; Conti, B.; Koob, G. F.; Zorrilla, E. P. CRF system recruitment mediates dark side of compulsive eating. Proceedings of the National Academy of Sciences of the United States of America 2009, 106, 20016-20020.
[View]