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The Journal of Neuroscience, March 1, 2003, 23(5):1859

Optical Imaging of Long-Term Depression in the Mouse Cerebellar Cortex In Vivo

Wangcai Gao¹, Robert L. Dunbar¹, Gang Chen¹, Kenneth C. Reinert¹, John Oberdick², and Timothy J. Ebner¹

¹ Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, and ² Department of Neuroscience and the Neurobiotechnology Center, The Ohio State University College of Medicine, Columbus, Ohio 43210

Conjunctive stimulation of climbing fiber and parallel fiber inputs results in long-term depression (LTD) at parallel fiber-Purkinje cell synapses. Although hypothesized to play a major role in cerebellar motor learning, there has been no characterization of the cellular and molecular mechanisms of LTD in the whole animal, let alone its spatial properties, both of which are critical to understanding the role of LTD in cerebellar function. Neutral red optical imaging of the cerebellar cortex in the anesthetized mouse was used to visualize the spatial patterns of activation. Stimulation of the parallel fibers evoked a transverse beam of optical activity, and stimulation of the contralateral inferior olive evoked parasagittal bands. Conjunctive stimulation of parallel fibers and climbing fibers induced a long-term decrease (at least 1 hr) in the optical response to subsequent parallel fiber activation confined to the region of interaction between these two inputs. Activation of climbing fibers alone failed to induce the long-term decrease. Field potential recordings confirmed that the depression is postsynaptic and restricted to the interaction site. The long-term depression in the beam was prevented by a group 1 metabotropic glutamate receptor (mGluR₁) antagonist and was absent in transgenic mice selectively expressing an inhibitor of protein kinase C (PKC) in Purkinje cells. Conversely, the long-term depression occurred in the mGluR₄ knock-out mouse, consistent with its postsynaptic origin. In addition to providing the first visualization of parallel fiber-Purkinje cell LTD in the cerebellar cortex, this study demonstrates the spatial specificity of LTD and its dependence on mGluR₁ and PKC in vivo.

Key words: long-term depression; optical imaging; neutral red; cerebellum; mGluR; protein kinase C; parallel fiber; Purkinje cell

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Copyright © 2003 Society for Neuroscience  0270-6474/03/2351859-08$05.00/0

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