| First Author | Lewitus GM | Year | 2014 |
| Journal | J Neurosci | Volume | 34 |
| Issue | 18 | Pages | 6146-55 |
| PubMed ID | 24790185 | Mgi Jnum | J:210602 |
| Mgi Id | MGI:5571516 | Doi | 10.1523/JNEUROSCI.3481-13.2014 |
| Citation | Lewitus GM, et al. (2014) An adaptive role of TNFalpha in the regulation of striatal synapses. J Neurosci 34(18):6146-55 |
| abstractText | Elevation of inflammatory cytokines in the striatum precedes symptoms in a number of motor dysfunctions, but it is unclear whether this is part of the disease process or an adaptive response to the pathology. In pyramidal cells, TNFalpha drives the insertion of AMPA-type glutamate receptors into synapses, and contributes to the homeostatic regulation of circuit activity in the developing neocortex. Here we demonstrate that in the mouse dorsolateral striatum, TNFalpha drives the internalization of AMPARs and reduces corticostriatal synaptic strength, dephosphorylates DARPP-32 and GluA1, and results in a preferential removal of Ca(2+)-permeable AMPARs. Striatal TNFalpha signaling appears to be adaptive in nature, as TNFalpha is upregulated in response to the prolonged blockade of D2 dopamine receptors and is necessary to reduce the expression of extrapyramidal symptoms induced by chronic haloperidol treatment. These data indicate that TNFalpha is a regulator of glutamatergic synaptic strength in the adult striatum in a manner distinct from its regulation of synapses on pyramidal cells and mediates an adaptive response during pathological conditions. |
