Department of Pharmacology
- Investigating the Role of Astrocyte Signaling in Brain Function
Approximately 50% of the mammalian brain is composed of astrocytes. These cells are present in every region of brain, are always closely associated with neuronal elements, and exhibit a wide variety of morphological phenotypes and neurotransmitter receptors. It is striking that while these cells constitute the largest single population of cells in brain, we know very little concerning their role in brain function. Many neurobiologists believe that astrocytes play a critical role in buffering extracellular potassium levels within the narrow range required for neuronal activity. Similarly, astrocytes are thought important in removing glutamate following its release at neuronal synapses.
A primary goal of our laboratory is to determine how astrocytes and neurons are signaling one another and the functional outcome of neuron astrocyte conversation. Our working hypothesis is that there are microdomains within astrocytic syncytium that interact with neuronal synapses to facilitate or to dampen neuronal excitability and/or neurotransmission. Through a combination of 2-photon imaging in live animals, electrophysiological, and behavioral studies using genetically-engineered mice we hope to begin unraveling the role of these cells in neurophysiology and disease.
Click above for PubMed publications.
- Agulhon, C., Fiacco, T.A., McCarthy, K.D. Hippocampal Short- and Long-term Plasticity are not Modulated by Astrocyte Ca2+ Signaling. (2010) Science 327(5970): 1250-1254. Free access to: abstract or full text article in Science online.
- Fiacco, T.A., Agulhon, C., McCarthy, K.D. (2009) Sorting out astrocyte physiology from pharmacology. Annu. Rev. Pharmacol. Toxicol 49: 151-174. Abstact
- Agulhon, C., Petravicz, J., McMullen, A.B., Sweger, E.J., Minton, S.K., Taves, S.R., Casper, K.B., Fiacco, T.A., McCarthy, K.D. (2008) What is the role of astrocyte calcium in neurophysiology? Neuron 25: 932-46. Abstract
- Petravicz, J., Fiacco, T.A., McCarthy, K.D. (2008) Loss of IP3 receptor-dependent Ca2+ increases in hippocampal astrocytes does not affect baseline CA1 pyramidal neuron synaptic activity. J. Neurosci. 28:4967-73. Abstract
- Djukic, B., Casper, K.B., Philpot, B.D., Chin, L.S., McCarthy, K.D. (2007) Conditional knock-out of Kir4.1 leads to glial membrane depolarization, inhibition of potassium and glutamate uptake, and enhanced short-term synaptic potentiation. J. Neurosci. 27:11354-65. Abstract
- Fiacco, T.A., Agulhon, C., Taves, S.R., Petravicz, J., Casper, K.B., Dong, X., Chen, J., McCarthy, K.D. (2007) Selective stimulation of astrocyte calcium in situ does not affect neuronal excitatory synaptic activity. Neuron 24:611-625. Abstract
- Casper, K.B., and McCarthy, K.D. GFAP-positive progenitor cells produce neurons and oligodendrocytes throughout the CNS. (2006) Mol Cell Neurosci 31: 676-684. Abstract
- Sweger, E.J., Casper, K.B., Scearce-Levie, K., Conklin, B.R., and McCarthy, K.D. (2007) Development of hydrocephalus in mice expressing the G(i)-coupled GPCR Ro1 RASSL receptor in astrocytes. J. Neurosci. 27:2309-17.
- Pascual, O., Casper, K., Kubera, C., Zhang, J., Revilla-Sanchez, R., Sul, J-Y., Takano, H., Moss, S.J., McCarthy, K.D., and Haydon, P.G. (2005) Astrocyte purinergic signaling coordinates synaptic networks. Science 310: 113-116. Abstract
- Fiacco, T.A., and McCarthy, K.D. (2004) Intracellular astrocyte calcium waves in situ increase the frequency of spontaneous AMPA receptor currents in CA1 pyramidal neurons. J Neurosci 24: 722-32. Abstract
- Lin, W., Kemper, A., McCarthy, K.D., Pytelm P., Wangm, J.P., Campbell, I.L., Utset, M.F., and Popko, B. (2004) Interferon-gamma induced medulloblastoma in the developing cerebellum. J Neurosci 24: 10074-83. Abstract
- Nett, W.J., Oloff, S.H., and McCarthy, K.D. (2002) Hippocampal astrocytes in situ exhibit calcium oscillations that occur independent of neuronal activity. J Neurophysiol 87(1): 528-537. Abstract