McCarthy Lab Paper Published in Science & Highlighted in Nature

 The paper, titled "Hippocampal Short- and Long-Term Plasticity Are Not Modulated by Astrocyte Ca²⁺ Signaling," calls into question the accepted paradigm that non-neuronal glial cells influence neuronal function by releasing calcium-dependent chemical messangers (gliotransmitters) at synapses, affecting synaptic transmission.

Summary: For the past decade it has been widely accepted that astrocytes release neuroactive molecules (gliotransmitters) affecting synaptic transmission.  This process is generally accepted to be a Ca2+ dependent process.  Cendra Agulhon used two mouse lines to either selectively increase or obliterate astrocytic Gq G protein-coupled receptor Ca2+ signaling to further test this hypothesis.  She found that neither increasing nor obliterating astrocytic Ca2+ fluxes affect spontaneous and evoked excitatory synaptic transmission or synaptic plasticity, indicating that the mechanism of gliotransmission needs to be reconsidered.

The paper was published in Science on March 5, 2010 along with a commentary, and highlighted in Nature March 11, 2010 and Nature Revew Neuroscience in  the May 10, 2010 issue.  Cendra Agulhon, pictured above right, is first author on the paper.  Dr. Ken McCarthy and Todd Fiacco are co-authors. 

The high impact of this work is evidenced by its publication in Science, it being highlighted in Nature and Nature Review Neuroscience and a commentary published in Science.

Full-text article in Science online.

Highlighting of paper in Nature

Highlighting of the paper in Nature Review Neuroscience

Commentary in Science online

Cendra's interview in the Scientist blog

Cendra's interview in Chemical & Engineering News

Cendra quoted in article on glial cell research in The Boston Globe

Cendra's interview in Science en Vie (in French)

For free access to full text online article or abstract:  Go to McCarthy faculty page, scroll to publications and the links are at the end of the citation for the Science article.

Figure Legend: Confocal image of an astrocyte (green) extending ramified processes that contact CA1 neuronal dendrites (red) within the stratum radiatum of hippocampus.

Astrocytes exhibit a large number of G_q G protein-coupled receptors (G_q GPCRs) linked to calcium mobilization from internal stores. While these receptors are activated by neurotransmitters released from presynaptic terminals, astrocytic G_q GPCR calcium signaling does not modulate hippocampal synaptic transmission and plasticity. The neurophysiological outcome of neuron-to-astrocyte G_q GPCR calcium signaling remains unknown.

Click image for enlargement.

Movie Legend: Stimulation of MrgA1R, a G_q GPCR selectively expressed in astrocytes of genetically modified mice, trigger Ca²⁺ increases not only in the soma and thick processes but also in astrocyte fine processes, as reported previously.

The movie below shows a patch-loaded astrocyte with OGB-1 Ca2+ indicator for filling small cellular compartments. Stimulation of MrgA1Rs evokes astrocytic Ca2+ increases not only in the soma and thick processes but also in astrocyte fine processes. While individual fine processes cannot be resolved using confocal microscopy, Ca2+ was clearly monitored in small territories of astrocyte fine processes which appear as a “cloud” or fine fuzz above background surrounding thick processes.