Cell Biology and Neuroscience

Phone: (951) 827-7865
Fax: (951) 827-3087
Office Location: 1109 Biological Sciences
Office Hours:
Email: todd.fiacco@ucr.edu

Todd A. Fiacco, Ph.D.

Biography

The overall research goal of the lab is to elucidate the function of astrocytes in synaptic signaling during normal physiological brain activity and also during brain pathology. Although astrocytes have been known for many years to possess numerous metabotropic receptors of the G_i, G_s, and G_q families that bind and respond to synaptically-released neurotransmitter, the function of these receptors has remained unclear. Activation of astrocytic Gq GPCRs both in situ and in vivo can be visualized using indicator dyes that detect changes in intracellular Ca²⁺ concentration following release of Ca²⁺ from IP₃ receptor-sensitive internal stores. Visualization of astrocyte Ca²⁺ provides a readout of Gq GPCR signaling activity in the cell. The research questions currently being studied in the lab include: 

• What is the level of synaptic activity required to elicit an astrocytic Gq GPCR response?
• Once this level has been reached, do astrocytes respond in a whole-cell or microdomain manner? 
• Are microdomains driven by neuronal activity or constitutive (basal) GPCR signaling activity in the absence of ligand?
• Do astrocytic GPCRs exhibit short- or long-term plasticity? 

Evidence out of my lab suggests that astrocytic GPCRs and their signaling molecules play an important role in the rapid modulation of glutamate and potassium uptake, two critical astrocyte functions. We have also obtained data suggesting that astrocytic Gq GPCRs exhibit a homeostatic-like plasticity in response to long-term changes in neuronal firing rates. 

In collaboration with Dr. Devin Binder (http://www.binderlab.com/index.php?cID=1), the lab has begun to explore the role of astrocytes in epilepsy. Astrocytes may actively participate in the generation of seizures involving mechanisms that do not require G_q GPCR-driven Ca²⁺ elevations, but rather by a series of events occurring as a result of changes in astrocyte volume. 

Figure caption: An astrocyte (green) and a CA1 pyramidal neuron (red) in an acute hippocampal slice patch-clamped with Alexa 488 and Alexa 568 hydrazide dyes, respectively.

Publications

• Agulhon C, Sun M-Y, Murphy T, Myers T, Lauderdale K, Fiacco TA. Calcium signaling and gliotransmission in normal versus reactive astrocytes. Frontiers in Pharmacology 3:139, 2012.
• Pontrello CG, Sun MY, Lin A, Fiacco TA, DeFea KA, Ethell IM. Cofilin under arrest: a new role for β-arrestin-2 in NMDA-dependent dendritic spine plasticity, LTD and learning. PNAS 109(7): 442-51, 2012.
• Agulhon C, Fiacco TA, McCarthy KD. Hippocampal short- and long-term plasticity are not modulated by astrocyte calcium signaling. Science 327(5970):1212-3, 2010.
• Fiacco TA, Agulhon C, McCarthy KD. Sorting out astrocyte physiology from pharmacology. Annu Rev Pharmacol Toxicol. 49: 151-74, 2009.
• Agulhon C, Petravicz J, McMullen AB, Sweger EJ, Minton SK, Taves SR, Casper KB, Fiacco TA, McCarthy KD. What Is the Role of Astrocyte Calcium in Neurophysiology? Neuron 59(6): 932-946, 2008.
• Fiacco TA, Agulhon C. Advances in understanding new roles for astrocytes in the modulation of neuronal activity. Physiology News 72: 18-20, 2008.
• Fiacco TA, Casper K, Agulhon C, Sweger E, Taves S, Minton S, McCarthy KD. Molecular approaches for studying astrocytes. In: Astrocytes in (patho)Physiology of the Nervous System, Springer ( Boston , MA ); Edited by Vladimir Parpura and Phil Haydon, pp. 383-406, 2008.
• Petravicz J, Fiacco TA, McCarthy KD. Loss of IP3 receptor-dependent Ca2+ increases in hippocampal astrocytes does not affect baseline CA1 pyramidal neuron synaptic activity. Journal of Neuroscience 28(19):4967-73, 2008.
• Djukic B, Fiacco TA, McCarthy KD. Astrocyte signaling systems in physiology and pathology. In: Immune and Glial Regulation of Pain, edited by Joyce A. DeLeo, Linda S. Sorkin, and Linda R. Watkins, IASP Press, Seattle, pp.229-247, 2007.
• Fiacco TA, Agulhon C, Taves S, Petravicz J, Casper K, Dong Xinzhong, Chen J, McCarthy KD. Selective stimulation of astrocyte calcium in situ does not affect neuronal excitatory synaptic activity. Neuron 54:611-626, 2007.
• Fiacco TA, McCarthy KD. Astrocyte calcium elevations: Properties, propagation, and effects on brain signaling. Glia 54(7):676-690, 2006.
• Fiacco TA, McCarthy KD. Intracellular astrocyte calcium waves in situ increase the frequency of spontaneous AMPA receptor currents in CA1 pyramidal neurons. Journal of Neuroscience 24:722-732, 2004.
• Fiacco TA, Rosene DL, Galler JR, Blatt GJ. Increased density of hippocampal kainate receptors but normal density of NMDA and AMPA receptors in a rat model of prenatal protein malnutrition. Journal of Comparative Neurology 456:350-360, 2003.
• Tonkiss J, Shultz P, Shumsky JS, Fiacco TA, Vincitore M, Rosene DL, and JR Galler. hlordiazepoxide-induced spatial learning deficits: dose-dependent differences following prenatal malnutrition. Pharmacology, Biochemistry, and Behavior 65(1):105, 1999.