Endocannabinoid-Dependent Synaptic Plasticity in the Striatum

Atwood, Brady K.; Lovinger, David M.

doi:10.1007/978-3-319-57371-7_5

Cited by 1 publication

(1 citation statement)

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“…This finding is consistent with previous reports showing that activation of Group I mGluRs can mediate both LTD and LTP in the striatum (Sung et al, 2001;Gubellini et al, 2003;Lüscher and Huber, 2010). The mechanisms underlying striatal LTD are largely disputed, particularly regarding LTD at cortico-dSPN versus cortico-iSPN synapses, but in general, it is thought that postsynaptic Group I mGluR and L-type Ca 21 channel activation results in the mobilization of eCBs that bind presynaptic CB1Rs to suppress glutamate release (Gerdeman et al, 2002;Kreitzer and Malenka, 2007;Atwood and Lovinger, 2017). Studies have shown that pharmacological activation of Group I mGluRs is sufficient to induce eCB-mediated LTD and that blocking Group I mGluRs prevents LTD induction (Calabresi et al, 1999;Sung et al, 2001;Kreitzer and Malenka, 2007;Shen et al, 2008;Yin et al, 2008;Chepkova et al, 2009;Fino and Venance, 2010;Trusel et al, 2015).…”

Section: Adenosine and Glutamate Gate Hfs-ltd At Direct Corticostriatal Synapsessupporting

confidence: 91%

Astrocyte Signaling Gates Long-Term Depression at Corticostriatal Synapses of the Direct Pathway

et al. 2020

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Despite extensive research into understanding synaptic mechanisms of striatal plasticity, the functional role played by astrocytes in this region remains to be fully elucidated. It was recently demonstrated that high-frequency stimulation (HFS) of cortical inputs induced long-term depression (LTD) mediated by adenosine A1 receptor (A1R) activation at corticostriatal synapses of the direct pathway [cortico-striatal projection neuron (dSPN)] in the dorsolateral striatum (DLS). Because astrocyte-derived adenosine has been shown to regulate synaptic transmission in several brain areas, we investigated whether this form of neuron-astrocyte signaling contributes to synaptic plasticity in the DLS of male and female mice. We found that cortical HFS increases calcium (Ca 21 ) levels in striatal astrocytes through activation of metabotropic glutamate receptor type 5 (mGluR5) signaling and that this astrocyte-mediated response is necessary for A1R-mediated LTD. Consistent with this, astrocyte activation with G q designer receptors exclusively activated by designer drugs (DREADDs) induced A1R-mediated synaptic depression at cortico-dSPN synapses. Together, these results indicate that astrocytes are integral elements of striatal A1Rmediated LTD.

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