John and Rebecca Moores Professor
Department of Biology and Biochemistry
Office: HSC 356
Contact: email@example.com - (713) 743-8381
Education: Ph.D., University of Texas at Austin
A number of properties of a neuron change in a coordinated fashion to store a given type of memory. Our long-term goal is to determine which properties of neurons change, and how these properties are regulated during formation of memories. Plasticity of glutamatergic synapses is important in the storage of information in the brain. Neuronal and glial plasma membrane glutamate transporters play major roles in removing released glutamate from the synaptic cleft. Although the function of glutamate transporters has received considerable attention, only recently did we demonstrate that glutamate uptake is regulated during expression of long-term synaptic plasticity. Glutamate uptake is increased during long-term sensitization in Aplysia, during long-term potentiation (LTP) in the hippocampus of the rat, and during morphine addiction and withdrawal in the rat. These findings suggest that long-term regulation of glutamate uptake during changes in synaptic efficacy may be a phylogenetically conserved mechanism that occurs along with different types of synaptic plasticities. Furthermore, deficiencies in glutamate uptake have been implicated in a number of diseases including ALS, epilepsy, and Alzheimers. The immediate goal of our experiments is to elucidate the general principles and functions of regulation of synaptic glutamate uptake associated with synaptic plasticity. In our research, we focus on well-studied long-term learning in Aplysia (long-term sensitization and learning that food is inedible) and synaptic plasticities in the hippocampus of the rat associated with LTP.
Understanding how learning and memory are modulated is an important aspect of understanding how memories are formed. Emotional state, various environmental factors, and diseases of the nervous system can impact the formation of memory. The long-term goals of this part of our research are to define factors that normally modulate memory formation and to determine how these factors modulate learning and memory. In addressing these goals, we discovered that the circadian clock modulates a simple form of long-term memory, long-term sensitization of the tail-siphon withdrawal reflex in Aplysia. Animals form long-term memory when they are trained during the day but form much less memory when they are trained at night. However, short-term memory of the same behavior is formed equally well during the day and night. Our current experiments extend our previous research by investigating circadian modulation of other forms of memory and the mechanisms responsible for circadian modulation of long-term memory. One set of experiments is to determine the scope and function of circadian modulation of learning and memory. We will investigate circadian modulation of a more complex associative form of learning (learning that food is inedible), and we will investigate circadian modulation of learning in nocturnal species of Aplysia. A second set of experiments is to determine the neuronal circuitry involved in the circadian modulation of learning and memory. A third set of experiments is to determine whether the circadian clock modulates learning and memory through modulation of facilitatory serotonergic neurons in the learning and memory circuitry. A fourth set of experiments is to determine which biochemical and molecular events necessary for the induction of long-term memory in sensory neurons are responsible for the circadian modulation of memory. We will investigate circadian modulation of synthesis of ApC/EBP mRNA and activation of MAPK and PKA during the formation of memory. In addition to elucidating the modulation of learning and memory, this research will provide insights into how the circadian clock regulates its outputs to produce rhythms. Furthermore, knowing the mechanisms by which memory formation is modulated will aid attempts to improve memory as well as to treat diseases that affect memory.
- Collado MS, Lyons LC, Levenson JM, Khabour O, Pita-Almenar JD, Schrader L, Eskin A. (2007). In vivo regulation of an Aplysia glutamate transporter, ApGT1, during long-term memory formation. Journal of Neurochemistry, 100(5):1315-28.
- Pita-Almenar JD, Collado MS, Colbert CM, Eskin A. (2006). Different mechanisms exist for the plasticity of glutamate reuptake during early long-term potentiation (LTP) and late LTP. The Journal Of Neuroscience: The Official Journal Of The Society For Neuroscience, 26(41):10461-71.
- Lyons LC, Collado MS, Khabour O, Green CL, Eskin A. (2006). The circadian clock modulates core steps in long-term memory formation in Aplysia. The Journal Of Neuroscience: The Official Journal Of The Society For Neuroscience, 26(34):8662-71.
- Lyons LC, Rawashdeh O, Eskin A. (2006). Non-ocular circadian oscillators and photoreceptors modulate long term memory formation in Aplysia. Journal of Biological Rhythms, 21(4):245-55.
- Chin J, Liu RY, Cleary LJ, Eskin A, Byrne JH. (2006). TGF-beta1-induced long-term changes in neuronal excitability in aplysia sensory neurons depend on MAPK. Journal of Neurophysiology, 95(5):3286-90.
- Lyons LC, Rawashdeh O, Katzoff A, Susswein AJ, Eskin A. (2005). Circadian modulation of complex learning in diurnal and nocturnal Aplysia. Proceedings Of The National Academy Of Sciences Of The United States Of America, 102(35):12589-94.
- Khabour, O., Levenson, J., Lyons, L.C., Kategaya, L.S., Chin, J., Byrne, J.H. and Eskin, A. 2004. Co-regulation of glutamate uptake and long-term sensitization in Aplysia. J. Neuroscience, 24(40):8829-8837.
- Antzoulatos, A.G., Cleary, L.J., Eskin, A., Baxter, D.A. and Byrne, J.H. 2003. Desensitization of postsynaptic glutamate receptors contributes to high-frequency depression of Aplysia sensorimotor connection. Learning and Memory 10:309-313.
- Fernandez, R.I., Lyons, L.C., Levenson, J., Khabour, O. and Eskin , A. 2003. Circadian modulation of long-term sensitization in Aplysia. Proc. Natl. Acad. Sci. 100:14415-14420.
- Levenson, J., Weeber, E., Selcher, J.C., Kategaya, L.S., Sweatt, D. and Eskin, A. 2002. Long-term potentiation and contextual fear conditioning increase neuronal glutamate uptake. Nature Neuroscience 5: 155-161.
- Chin, J., Burdohan, J.A., Eskin, A. and Byrne, J.H. 2002. Inhibitor of glutamate transport alters synaptic transmission at sensorimotor synapses in Aplysia. J. Neurophysiology 87: 3165-3168.
- Chin, J., Angers, A., Cleary, L.J., Eskin, A. and Byrne, J.H. 2002. TGF-B1 alters synapsin distribution and modulates synaptic depression in Aplysia. J. Neuroscience 22: RC220 (1-6)
- Levenson, J., Weeber, E.J., Sweatt, J.D. and Eskin, A. 2002. Glutamate uptake in synaptic plasticity: from mollusk to mammal. Current Molecular Medicine 2:593-603.
- Hattar, S., Lyons, L.C., Dryer, L. and Eskin, A. 2002. Circadian regulation of the transcription factor, ApC/EBP, in the eye of Aplysia. J. Neurochem. 83:1401-1411.
- Blumenthal, E.M., Block, G.D. and Eskin, A. 2001. Cellular and molecular analysis of molluscan circadian pacemakers. Handbook of Behavioral Neurobiology: Circadian Clocks, Plenum Press (in press).
- Levenson, J., Sherry, D., Dryer, L., Chin, J., Byrne, J.H. and Eskin, A. 2000. Localization of glutamate and glutamate transporters in neurons of Aplysia . J. Comparative Neurology 423:121-131.
- Levenson, J., Endo, S., Fernandez, R., Kategaya, L., Byrne, J.H. and Eskin, A. 2000. Long-term regulation of neuronal high affinity glutamate and glutamine uptake in Aplysia . Proc. Natl. Acad. Sci. USA 97: 97:12858-63.
- Sloan, M.A., Levenson, J., Tran, Q., Kerbeshian, M., Block, G.D. and Eskin, A. 1999. Aging affects the ocular circadian pacemaker of Aplysia californica. J. Biol. Rhythms 14:151-159.
- Levenson, J., Byrne, J.H. and Eskin, A. 1999. Levels of serotonin in the hemolymph of Aplysia are modulated by light:dark cycles and sensitization training. J. Neuroscience 18:8094-8103
- Chin, J., Angers, A., Cleary, L., Eskin, A. and Byrne, J.H. 1999. TGF-B1 in Aplysia : Role in long-term changes in the excitability of sensory neurons and distribution of TBR-II-like immunoreactivity. Learning and Memory 6:31
- Sankrithi, N. and Eskin, A. 1999. Effects of cyclin-dependent kinase inhibitors on transcription and ocular circadian rhythm of Aplysia. J. Neurochem. 72:605-613
- Zwartjes, R.E., West, H., Hattar, S., Ren, X., Noel. F., Nunez-Regueiro, M., MacPhee, K., Homayouni, R., Crow, M.T., Byrne, J.H. and Eskin, A. Identification of specific mRNAs affected by treatments producing long-term facilitation in Aplysia. Learning