Edwin (Ted) G. Abel

faculty photo
Professor of Biology
Member, Center for Sleep and Circadian Neurobioloy, University of Pennsylvania
Member, Center for Neurobiology and Behavior, University of Pennsylvania
Member, Institute of Neurological Sciences, University of Pennsylvania
Affiliated Faculty, Institute for Research in Cognitive Science, University of Pennsylvania
Director, Biological Basis of Behavior Program, University of Pennsylvania
Program Director, NIMH Training Program in Behavioral and Cognitive Neuroscience, University of Pennsylvania
Member, Institute for Translational Medicine and Therapeutics
Department: Biology

Contact information
Smilow Center for Translational Research, Room 10-133
3400 Civic Center Blvd. Bldg. 421
Philadelphia, PA 19104-6168
Office: (215) 746-1122
Fax: (215) 573-7188
Lab: (215) 898-3100
B.A. (Chemistry)
Swarthmore College, 1985.
M.Phil. (Biochemistry)
University of Cambridge, Christ’s College, 1987.
Ph.D. (Biochemistry and Molecular Biology)
Harvard University, 1993.
Permanent link

Description of Research Expertise

Research Interests

The molecular basis of synaptic plasticity, sleep/wake regulation, learning and memory; mouse models of neurodevelopmental and psychiatric disorders

Key words: Memory storage; synaptic plasticity; long-term potentiation; behavior; sleep/wake states; genetically modified mice; epigenetics; cAMP signaling; autism; schizophrenia.

Description of Research

Research in the Abel lab focuses on the molecular mechanisms of memory storage and the molecular basis of neurodevelopmental and psychiatric disorders. Dr. Abel has been a leader in applying molecular and genetic approaches to define how neural circuits mediate behavior, making creative use of genetically modified mouse lines to study the biological basis of behavior. The three main areas of research in the Abel lab all derive from an interest in the ways in which information is stored in the brain. First, we have been examining the molecular and epigenetic mechanisms of long-term memory. We have identified ways to enhance memory, and we are seeking to define the molecular substrates underlying this cognitive enhancement with the hope that this will lead to novel therapeutic approaches for the debilitating cognitive impairments that accompany many neurological, psychiatric and neurodevelopmental disorders. Second, we have been examining the role of sleep in memory storage, defining the molecular mechanisms by which sleep deprivation impairs hippocampus-dependent memory. Recent work in the Abel lab has revealed that sleep deprivation alters synaptic connectivity in the hippocampus. Third, we are examining mouse models of schizophrenia and autism. We have recently identified male-specific deficits in reward learning in mouse models of autism, providing a potential way to explain the well-known male bias of this neurodevelopmental disorder.

Dr. Abel is Co-Director of the Biological Basis of Behavior Program, and he directs an NIMH-funded Graduate Training Program in Behavioral and Cognitive Neuroscience at Penn. He is the Faculty Director of the Neurobehavior Testing Core at Penn, and Editor-in-Chief of Neurobiology of Learning and Memory.

Molecular Mechanisms of Long-Term Memory Storage

Each neuron contains thousands of synapses, each of which needs to be independently modifiable by experience. Work in the Abel lab suggests that localized signaling mediated by scaffolding proteins generates synapse-specific activation of biochemical pathways that mediate long-term memory storage. Beginning as a postdoctoral fellow, Dr. Abel pioneered genetic approaches to define the role of the cAMP signaling and protein kinase A in hippocampal synaptic plasticity and memory. Most recently, his lab has focused on spatial compartmentalization of PKA signaling via a large family of A-kinase anchoring proteins (AKAPs), which restrict PKA and other signaling molecules to specific subcellular locations such as the plasma membrane where they interact with receptors, adenylyl cyclases, and ion channels. This research includes computational approaches to model spatially restricted signaling along with genetic and pharmacological approaches.

How are memories stored for months and even years in neural circuits in the brain? Recent work by the Abel lab has suggested that epigenetic modifications that act during development to define cell fate provide a biochemical mechanism for long-term memory storage. Histone acetylation, an activating epigenetic mark, plays a critical role in long-term memory. Decreasing histone acetylation by genetic deletion of the histone acetyltransferase CREB-binding protein (CBP) in the hippocampus reduces long-term memory performance, whereas increasing histone acetylation by pharmacological inhibition of histone deacetylases (HDACs) or genetic deletion of the co-repressor SIN3a enhances long-term memory. We have found the Nr4a family of genes is downstream of CBP-mediated histone acetylation and required for the enhancement of memory by HDAC inhibition. We are studying the transcriptional regulators mediating long-term memory through mouse models and the genetic targets of histone acetylation using genome-wide techniques.

Sleep and Memory

Sleep facilitates the formation of hippocampus-dependent memories and brief periods of sleep deprivation are detrimental to memory consolidation.  Additionally, sleep is regulated by many of the same molecular processes that contribute to memory storage.  The Abel lab uses a combination of molecular, genetic, and viral approaches to elucidate the machinery underlying sleep-associated long-term memory consolidation.  Specifically, we have found sleep deprivation induces a cascade of changes in cAMP signaling and protein synthesis. We have also defined the role of gliotransmission in mediating the impact of sleep deprivation on memory and cognition. Given that in today’s society people obtain insufficient sleep, which in turn results in deleterious effects on cognitive function, our studies are critical to understand the molecular and cellular changes induced by sleep and sleep deprivation and their impact on memory consolidation.

The Molecular Basis of Neurodevelopmental and Psychiatric Disorders

Cognitive deficits accompany many neurological, psychiatric and neurodevelopmental disorders. The Abel lab is interested in using mouse models to understand the structural, behavioral, and genetic underpinnings of schizophrenia and autism spectrum disorder. In an effort to model autism spectrum disorder, we have conducted an extensive study of behavioral phenotypes in several mouse models. Our studies in operant learning tasks have revealed deficits in motivation and reward-based learning, processes that are mediated by the basal ganglia. Our investigation of striatal-based behaviors and learning may provide unique insights into the basis of autism spectrum disorder, revealing the importance of deficits in the neural circuitry that mediates reward. With these translational approaches, we hope to identify novel targets for the development of new therapeutics to treat psychiatric and neurodevelopmental disorders.

Description of Itmat Expertise

Research in the Abel lab focuses on the molecular mechanisms of memory storage, with the goal of developing novel therapeutic approaches to treat the cognitive deficits that accompany many neurological and psychiatric disorders

Selected Publications

Peixoto Lucia L, Wimmer Mathieu E, Poplawski Shane G, Tudor Jennifer C, Kenworthy Charles A, Liu Shichong, Mizuno Keiko, Garcia Benjamin A, Zhang Nancy R, Giese K, Abel Ted: Memory acquisition and retrieval impact different epigenetic processes that regulate gene expression. BMC genomics 16 Suppl 5: S5, 2015.

Peixoto Lucia, Risso Davide, Poplawski Shane G, Wimmer Mathieu E, Speed Terence P, Wood Marcelo A, Abel Ted: How data analysis affects power, reproducibility and biological insight of RNA-seq studies in complex datasets. Nucleic acids research 43(16): 7664-74, Sep 2015.

Angelakos Christopher C, Abel Ted: Molecular Genetic Strategies in the Study of Corticohippocampal Circuits. Cold Spring Harbor perspectives in biology 7(7): a021725, Jul 2015.

Weljie Aalim M, Meerlo Peter, Goel Namni, Sengupta Arjun, Kayser Matthew S, Abel Ted, Birnbaum Morris J, Dinges David F, Sehgal Amita: Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt. Proceedings of the National Academy of Sciences of the United States of America 112(8): 2569-74, Feb 2015.

Havekes Robbert, Bruinenberg Vibeke M, Tudor Jennifer C, Ferri Sarah L, Baumann Arnd, Meerlo Peter, Abel Ted: Transiently increasing cAMP levels selectively in hippocampal excitatory neurons during sleep deprivation prevents memory deficits caused by sleep loss. The Journal of neuroscience : the official journal of the Society for Neuroscience 34(47): 15715-21, Nov 2014.

Patel Tapan P, Gullotti David M, Hernandez Pepe, O'Brien W Timothy, Capehart Bruce P, Morrison Barclay, Bass Cameron, Eberwine James E, Abel Ted, Meaney David F: An open-source toolbox for automated phenotyping of mice in behavioral tasks. Frontiers in behavioral neuroscience 8: 349, 2014.

Hawk Joshua D, Bookout Angie L, Poplawski Shane G, Bridi Morgan, Rao Allison J, Sulewski Michael E, Kroener Brian T, Manglesdorf David J, Abel Ted: NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors. The Journal of clinical investigation 122(10): 3593-602, Oct 2012.

Havekes Robbert, Canton David A, Park Alan J, Huang Ted, Nie Ting, Day Jonathan P, Guercio Leonardo A, Grimes Quinn, Luczak Vincent, Gelman Irwin H, Baillie George S, Scott John D, Abel Ted: Gravin orchestrates protein kinase A and β2-adrenergic receptor signaling critical for synaptic plasticity and memory. The Journal of neuroscience : the official journal of the Society for Neuroscience 32(50): 18137-49, Dec 2012.

Halassa Michael M, Florian Cedrick, Fellin Tommaso, Munoz James R, Lee So-Young, Abel Ted, Haydon Philip G, Frank Marcos G: Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss. Neuron 61(2): 213-9, Jan 2009.

Vecsey Christopher G, Baillie George S, Jaganath Devan, Havekes Robbert, Daniels Andrew, Wimmer Mathieu, Huang Ted, Brown Kim M, Li Xiang-Yao, Descalzi Giannina, Kim Susan S, Chen Tao, Shang Yu-Ze, Zhuo Min, Houslay Miles D, Abel Ted: Sleep deprivation impairs cAMP signalling in the hippocampus. Nature 461(7267): 1122-5, Oct 2009.

back to top
Last updated: 10/26/2015
The Trustees of the University of Pennsylvania