UCR

Cell Biology and Neuroscience



Todd A. Fiacco


Todd Fiacco
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.

Assistant Professor

Biography

The overall research goal of the lab is to elucidate the function of astrocytes in brain physiology and pathology. There are two main research objectives:

1. To understand the properties and function of astrocytic receptors and the purpose of neuron-to-astrocyte receptor signaling in the brain.

2. To understand astrocytic mechanisms controlling neuronal excitability.

Astrocytes express numerous metabotropic receptors (a.k.a. G protein-coupled receptors or GPCRs) of the Gi, Gs, and Gq families, but the function of these receptors has remained controversial and unclear. Neurons can activate astrocytic GPCRs in situ and in vivo by release of neurotransmitter during synaptic activity. We use calcium indicator dyes to visualize activation of astrocytic Gq GPCRs in acute hippocampal slices following low-level or local stimulation of Schaffer collaterals. To date, while it is clear that neurons can stimulate astrocyte receptors, the level of neuronal activity that can elicit an astrocyte response is not well understood. Nor is it clear if the astrocytic response remains confined to a local domain, such as an astrocyte process or microdomain, or propagates over a larger area of the cell and/or includes the cell soma. We are actively performing experiments to answer these questions. In addition, we are exploring the effect of stimulating astrocytic GPCRs and their signaling molecules on the rapid modulation of glutamate and potassium uptake, two critical astrocyte functions. Up- or downregulation of astrocyte potassium and glutamate uptake may alter glutamate or K+ concentrations near the synapse, with possible effects on neuronal excitatory synaptic or extrasynaptic activity.

The lab is also studying plasticity of astrocytic receptors at both the whole-cell and microdomain levels. Findings gathered to date suggest that astrocytic Gq GPCRs rapidly (within hours) scale up or down in acute hippocampal slices in response to long-term changes in neuronal firing rates. Having an understanding of how astrocytic receptor signaling is affected by changes in neuronal activity has important implications for both normal synaptic function as well as processes underlying neurological disorders and neurodegenerative disease. 

In collaboration with the Devin Binder Lab (http://www.binderlab.com/index.php?cID=1), we have begun to explore the role of astrocytes in epilepsy. Astrocytes may actively participate in the generation of seizures involving mechanisms that do not require Gq GPCR-driven Ca2+ elevations, but rather by a series of events occurring as a result of changes in astrocyte volume. We are also interested in determining the changes taking place in reactive astrocytes at the molecular level over the course of epileptogenesis. 

astrocyte

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

Publications

  • Xie AX, Lauderdale K, Murphy T, Myers TL, Fiacco TA. Inducing plasticity of astrocytic receptors by manipulation of neuronal firing rates. J Vis Exp (85), doi: 10.3791/51458, 2014.
  • Sun MY, Devaraju P, Xie AX, Holman I, Samones E, Murphy TR, Fiacco TA. Astrocyte calcium microdomains are inhibited by Bafilomycin A1 and cannot be replicated by low-level Schaffer collateral stimulation in situ. Cell Calcium, 55(1): 1-16, 2014.
  • Davila D, Karine Thibault K, Fiacco TA, Agulhon C. Recent molecular approaches to understanding astrocyte function in vivo. Front Cell Neurosci, 7: 272, 2013. 
  • Hubbard JA, Hsu MS, Fiacco TA, Binder DK. Glial cell changes in epilepsy: Overview of the clinical problem and therapeutic opportunities. Neurochemistry International, 63(7): 638-51, 2013. 
  • Devaraju P, Sun MY, Myers TL, Lauderdale K, Fiacco TA. Astrocytic group I mGluR-dependent potentiation of astrocytic glutamate and potassium uptake. J. Neurophysiol. 109:2404-14, 2013.
  • Xie AX, Sun MY, Murphy T, Lauderdale K, Tiglao E, Fiacco TA. Bidirectional scaling of astrocytic metabotropic glutamate receptor signaling following long-term changes in neuronal firing rates. PLoS One 7(11):49637, 2012. 
  • 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): 1-16, 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.
  • 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, 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.
  • 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.

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Cell Biology and Neuroscience
2109 Biological Science

David Eastmond: Chair of Cell Biology & Neurosience
Tel: (951) 827-4497
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E-mail: david.eastmond@ucr.edu

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