Sleep Research Society &
American Academy of Sleep Medicine
Undergraduate, Graduate and Postgraduate Training Opportunities
in Basic and Clinical Sleep Research and Sleep Medicine
2001 - V Edition
University of Pennsylvania
Department of Biology
319 Leidy Labs, 38th and Hamilton Walk,
University of Pennsylvania
Philadelphia, PA 19104-6018
Faculty (Name, Email address):
Types of Training Available
Types of Funding Available
Current Trainees (Names and Email address)Predoctoral Fellows:
Laurel Graves (email@example.com): MD, PhD student
Kevin Hellman (firstname.lastname@example.org): PhD Student
Trainees who have completed training [in the past five years] and current status (Name, Title, Institution, Email)
Primary Research and/or Clinical Focus of Laboratory
Technical Capabilities of Lab
Primary Training Focus
Other Training Opportunities
At Penn, other training opportunities are available through the Center for Sleep and Respiratory Neurobiology, Allan Pack, MD, PhD, Director, http://www.med.upenn.edu/sleepctr/
Representative Publications For the Last Five Years
Mayford, M., Abel, T. and Kandel, E. R. (1995). Transgenic approaches to cognition. Curr. Opin. Neurobiol. 5: 141-148.
Abel, T., Alberini, C., Ghirardi, M., Huang, Y.-Y., Nguyen, P. and Kandel, E. R. (1995). Steps toward a molecular definition of memory consolidation. In Schachter, D. (ed.), Memory Distortion. Harvard University Press, Cambridge, Mass., pp. 298-325.
Nguyen, P. V., Alberini, C. M., Huang, Y.-Y., Ghirardi, M., Abel, T. and Kandel, E. R. (1995). Genes, synapses and long-term memory. In Ottoson, D. (ed.), Challenges and Perspectives in Neuroscience. Elsevier, Oxford, U.K., pp. 213-237.
Kandel, E. R. and Abel, T. (1995). Neuropeptides, adenylyl cyclase and memory storage. Science 268: 825-826.
Patterson, S. L., Abel, T., Deuel, T. A. S., Martin, K. C., Rose, J. C. and Kandel, E. R. (1996). Recombinant BDNF rescues deficits in basal synaptic transmission and hippocampal LTP in BDNF knockout mice. Neuron 16: 1137-1145.
Huang, Y.-Y., Nguyen, P. V., Abel, T. and Kandel, E. R. (1996). Long-lasting forms of synaptic potentiation in the mammalian hippocampus. Learning and Memory 3: 74-85.
Abel, T., Nguyen, P. V., Barad, M., Deuel, T. A. S., Kandel, E. R., and Bourtchouladze, R. (1997). Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory. Cell 88: 615-626.
Silva, A. J., Simpson, E. M., Takahashi, J. S., Lipp, H. P., Nakanishi, N., Wehner, J. M., Giese, K. P., Tully, T., Abel, T., Chapman, P. F., Fox, K., Grant, S., Itohara, S., Lathe, R., Mayford, M., McNamara, J. O., Morris, R. J., Picciotto, M., Roder, J., Shin, H. S., Slesinger, P. A., Storm, D. R., Stryker, M. P., Wang, Y. and Wolfer, D. P. (1997). Mutant mice and neuroscience: recommendations concerning genetic background. Neuron 19: 755-759.
Abel, T., Martin, K. C., Bartsch, D. and Kandel, E. R. (1998). Memory suppressor genes: Inhibitory constraints on the storage of long-term memory. Science, 279: 338-341.
Abel, T. and Kandel, E. R. (1998). Positive and negative regulatory mechanisms that mediate long-term memory storage. Brain Research Reviews, 26: 360-378.
Bourtchouladze, R., Abel, T., Berman, N., Gordon, R., Lapidus, K. and Kandel, E. R. (1998). Different training procedures for contextual memory in mice can recruit either one or two critical periods for memory consolidation that require protein synthesis and PKA. Learning and Memory 5: 365-374.
Cardin, J and Abel, T. (1999). Memory suppressor genes: Enhancing the relationship between synaptic plasticity and memory storage. J. Neurosci. Res. 58: 10-23.
Lattal, K. M. and Abel, T. (2000). Cellular and molecular mechanisms of learning and memory. In Reith, M.E.A. (ed.), Cerebral Signal Transduction: From First to Fourth Messengers. Humana Press, Totowa, New Jersey, pp. 27-71.
Nguyen, P. V., Abel, T., Kandel, E. R. and Bourtchouladze, R. (2000). Strain-dependent differences in LTP and hippocampus-dependent memory in inbred mice. Learning & Memory 7: 170-179.
Rotenberg, A., Abel, T., Hawkins, R. D., Kandel, E. R. and Muller, R. U. (2000). Parallel instabilities of LTP, place cells and learning caused by decreased protein kinase A activity. Journal of Neuroscience 20: 8096-8102.
Woo, N. H., Duffy, S. N., Abel, T. and Nguyen, P. V. (2000). Genetic and pharmacological demonstration of differential recruitment of cAMP-dependent protein kinases by synaptic activity. Journal of Neurophysiology, 84: 2739-2735.
Duffy, S. N., Craddock, K. J., Abel, T. and Nguyen, P. V. (2001). Environmental enrichment modifies the PKA-dependence of hippocampal LTP and improves hippocampus-dependent memory. Learning & Memory, 8: 26-34.
Graves, L., Pack, A. and Abel, T. (2001). Sleep and memory: A molecular perspective. Trends in Neurosciences, 24: 237-243.
Abel, T. and Lattal, K. M. (2001). Molecular mechanisms of memory acquisition, consolidation and retrieval. Curr. Opin. Neurobiol., 11: 180-187.
Nie, T. and Abel, T. (2001). Fear conditioning in inbred mouse strains: An analysis of the time course of memory. Behavioral Neuroscience, in press.
Wand, G., Levine, M., Zweifel, L., Schwindinger, W. and Abel, T. (2001). The cyclic AMP/protein kinase A signal transduction pathway modulates ethanol consumption and sedative effects of ethanol. Journal of Neuroscience, in press.
Lattal, K. M. and Abel, T. (2001). An immediate shock freezing deficit with discrete cues: A possible role for US processing mechanisms. Journal of Experimental Psychology: Animal Behavior Processes, in press.
Lattal, K. M. and Abel, T. (2001). Different requirements for protein synthesis in acquisition and extinction of spatial preferences and context-evoked fear. Submitted.
Graves, L., Hellman, K., Veasey, S., Blendy, J., Pack, A. and Abel, T. A role for CREB in sleep/wake regulation. Submitted.
www link for the Lab
Faculty Research Interests
Ted Abel, Ph.D. is an Assistant Professor of Biology at the University of Pennsylvania. His research focuses on three major areas: the molecular basis of long-term memory storage and the role of sleep in memory storage; and the molecular basis of sleep/wake regulation.
A. The Molecular Basis of Long-Term Memory Storage
Synaptic plasticity, the change in the strength of neuronal connections in the brain, is thought to underlie memory storage and may play a crucial role in a variety of neurological and mental disorders, including Alzheimer’s disease, mental retardation, epilepsy and depression. One goal of our research is to use transgenic mice to explore the molecular basis of synaptic plasticity and memory storage. Transgenic techniques can be used to express gene products designed to inhibit or enhance the activity of endogenous signaling pathways with a high degree of molecular specificity. The transgenic approach is spatially and temporally more restricted than the conventional gene knockout approach, thereby allowing for a more direct correlation between a behavioral deficit and neuronal function in the adult brain.
One form of synaptic plasticity that has received much attention is long-term potentiation (LTP), an activity-dependent form of synaptic enhancement. Like many forms of memory and synaptic plasticity, LTP in the hippocampus has distinct temporal phases. Long-lasting LTP differs from short-term potentiation in requiring protein kinase A (PKA) activity, protein synthesis and transcription. To explore the molecular basis and behavioral significance of long-lasting forms of synaptic plasticity, we have produced mice in which PKA activity in the hippocampus is reduced by the transgenic expression of R(AB), a dominant negative form of the regulatory subunit of PKA. R(AB) transgenic mice exhibit selective impairments in long-term contextual memory and long-lasting forms of hippocampal synaptic plasticity.
We are currently developing new lines of transgenic mice in which expression of the R(AB) transgene is temporally, quantitatively and spatially regulated to define precisely the role that PKA plays in memory acquisition, consolidation, retrieval and extinction. These temporally regulated transgenes will also allow us to distinguish between developmental and acute effects of the transgene. By using inducible systems to express transgenes that enhance the PKA system, we are exploring if long-term memory can be improved by increasing signaling through this pathway.
B. The Role of Sleep in Long-Term Memory Storage
We have recently extended our research on long-term memory to begin to examine the molecular processes underlying the role of sleep in the consolidation of hippocampus-dependent long-term memory. Sleep is involved in many physiological processes, and disturbances in sleep are a hallmark of many diseases, including psychiatric disorders, such as depression. We are interested in bridging past behavioral studies, which have shown that sleep is needed for the consolidation of memory, with current knowledge about the molecular mechanisms underlying memory storage. Mice are an ideal system with which to explore the relationship between sleep and memory consolidation. Our recent work has used genetic and pharmacological approaches in mice to demonstrate that PKA activity is critically important for long-term memory storage. There are striking parallels between the effects of sleep deprivation and the effects of pharmacological manipulation of the PKA signaling pathway on the consolidation of memory. Based on this, we are examining the role of the PKA signaling pathway in the behavioral effects of sleep deprivation on hippocampus-dependent tasks in mice using genetic, pharmacological, electrophysiological and behavioral approaches.
C, Molecular mechanisms of sleep/wake regulation:
The cyclic AMP (cAMP)-responsive element binding protein (CREB) is a stimulus-induced transcription factor that has been shown to be important for neuronal function. Phosphorylated CREB levels within the forebrain are higher in waking than in sleep, and levels of CRE-mediated transcription oscillate in the suprachiasmatic nucleus in a circadian fashion. However, whether CREB regulates the sleep/wake cycle or alters circadian rhythms in mammals is unknown. To explore this question, we examined behavioral state and circadian parameters in mice lacking the a face D isoforms of CREB. NREM and REM sleep, as well as total sleep time, was significantly increased in CREB mutant mice, and time awake was decreased. The homeostatic response of CREB mutant mice to sleep deprivation revealed by increases in REM sleep (REM sleep rebound) was altered compared to wildtype mice. Circadian period was unaffected by the mutation, but wheel-running activity was diminished in CREB a D mutant mice, paralleling the reductions in wakefulness. Our results suggest that the CREB protein contributes to the mechanisms by which wakefulness is maintained, and our analysis reveals a dissociation between the homeostatic maintenance of sleep/wake states and the homeostatic response to sleep deprivation.