Research Interests
Dr. Thayer's laboratory studies neurodegenerative processes. His group uses electrophysiological and optical techniques to measure ion currents, to image synaptic proteins and to record changes in intracellular calcium within single neurons grown in tissue culture. Current research efforts focus on three principal areas.
1) Calcium is an essential second messenger involved in neurotransmitter release, gene regulation, and synaptic plasticity. Inappropriate elevation of the intracellular calcium concentration contributes to the neurodegeneration associated with AIDS, ischemia, epilepsy and head trauma. Thus, neurons have developed a complex system to maintain calcium homeostasis. Current studies focus on the modulation of processes that remove calcium from the cytoplasm by drugs and second messengers.
2) Synapse loss occurs early in neurodegenerative disease and correlates with cognitive decline in patients with HIV-1 associated dementia and Alzheimer’s disease. Recent studies indicate that loss of synapses is not an early step leading to the cell’s demise but instead, is a coping mechanism to reduce excess excitotoxic input. Current studies employ in vitro models to evaluate pharmacological strategies to prevent loss or induce recovery of synapses during neurotoxic processes.
3) Cannabinoids, analogs of the psychoactive ingredient in marijuana, act on receptors that are part of an endogenous signaling system. Endocannabinoid signaling serves as an on-demand neuroprotective mechanism. Currents studies examine the role of the endocannabinoid system in regulating synaptic transmission and neurotoxicity.
Drugs to slow the progression of neurodegenerative disease are lacking. Agents that modulate calcium signals, possibly via the endocannabinoid system, may protect synapses and cells from neurotoxic insult.
Selected papers:
Roloff AM, Anderson GR, Martemyanov KA, Thayer SA. (2010) Homer 1a gates the induction mechanism for endocannabinoid-mediated synaptic plasticity. J. Neurosci.
Ferragamo MJ, Reinardy JL, Thayer SA. (2009) Ca2+-dependent, stimulus-specific modulation of the plasma membrane Ca2+ pump in hippocampal neurons. J Neurophysiol.
Roloff, A. M. and Thayer, S. A. (2009) Modulation of excitatory synaptic transmission by Δ9-tetrahydrocannabinol switches from agonist to antagonist depending on firing rate. Molec. Pharmacol.
Kim, H. J. and Thayer, S. A. (2009) Lithium Increases Synapse Formation between Hippocampal Neurons by Depleting Phosphoinositides. Molec. Pharmacol.
Shideman, C. R., Reinardy J.L. and Thayer, S. A. (2009) γ-Secretase Modulates Store Operated Ca²+ Entry into Rat Sensory Neurons. Neurosci. Lett. 451:124-8
Kim, H. J., Martemyanov K. A. and Thayer, S. A. (2008) Human Immunodeficiency Virus Protein Tat Induces Synapse Loss via a Reversible Process that is Distinct from Cell Death J. Neurosci. 28:12604-13.
Kim, H. J., Waataja, J. J and Thayer, S. A. (2008) Cannabinoids inhibit network-driven synapse loss between hippocampal neurons in culture J. Pharmacol. Exp. Ther.
325: 850-858
Waataja, J. J., Kim, H. K., Roloff, A. M. and Thayer, S. A. (2008) Excitotoxic loss of post-synaptic sites is distinct temporally and mechanistically from neuronal death J. Neurochem. 104: 364–375. |
