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The Journal of Neuroscience, February 23, 2005, 25(8):2108-2116; doi:10.1523/JNEUROSCI.4254-04.2005

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Cellular/Molecular
Metabotropic P2Y Purinoceptor-Mediated Presynaptic and Postsynaptic Enhancement of Cerebellar GABAergic Transmission

Fumihito Saitow,¹ Takayuki Murakoshi,¹ Hidenori Suzuki,¹ and Shiro Konishi²

¹Department of Pharmacology, Nippon Medical School, Tokyo 113-8602, Japan, and ²Institute for Biomedical Science, Waseda University, Tokyo 202-0021, Japan

Cerebellar GABAergic inhibitory transmission is under heterosynaptic control mediated by diverse chemical messengers. Here, we investigated roles of metabotropic P2Y purinoceptors (P2YRs) on GABAergic synapses between cerebellar interneurons and Purkinje cells (PCs). Activation of P2Y purinoceptors by two selective agonists, ADP and 2-methylthio-ADP (2MeSADP), elicited two distinct forms of synaptic plasticity of GABAergic transmission in the cerebellar cortex. First, the two agonists induced long-lasting enhancement of stimulation-evoked GABAergic IPSCs as well as GABA_A receptor currents in PCs. This effect was completely abolished by intracellular infusion of the Ca²⁺-chelating agent BAPTA. Measurements of intracellular Ca²⁺ ([Ca²⁺]_i) dynamics showed that puff application of 2MeSADP produced an increase in [Ca²⁺]_i of PCs and that this increase persisted in an external Ca²⁺-deficient medium. These results suggest that P2Y activation postsynaptically elicits long-term enhancement of GABA_A receptor sensitivity of PCs through a G_q-mediated increase in [Ca²⁺]_i. The other action of P2YR agonists on cerebellar GABAergic synapses was that they produced a short-term increase in the frequency and the amplitude of spontaneous GABA_A receptor-mediated IPSCs in PCs in a manner sensitive to a P2Y₁R antagonist, N⁶-methyl 2'-deoxyadenosine 3',5'-bisphosphate. This action appeared to be attributable to an excitability increase in presynaptic GABAergic interneurons, because ADP excited all Lugaro cells examined and some of interneurons in the molecular layer. These results suggest that activation of cerebellar P2Y purinoceptors leads to modulation of GABAergic transmission in different spatial and temporal domains, namely short-term and long-term plasticity through presynaptic and postsynaptic mechanisms at interneuronPC inhibitory synapses in the rat cerebellar cortex.

Key words: cerebellum; Purkinje cell; purinergic; P2Y receptor; GABA; synaptic transmission

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Received Oct 13, 2004; revised January 18, 2005; accepted January 18, 2005.

This article has been cited by other articles:

				F. Saitow, M. Murano, and H. Suzuki Modulatory Effects of Serotonin on GABAergic Synaptic Transmission and Membrane Properties in the Deep Cerebellar Nuclei J Neurophysiol, March 1, 2009; 101(3): 1361 - 1374. [Abstract] [Full Text] [PDF]

				R. Piet and C. E. Jahr Glutamatergic and Purinergic Receptor-Mediated Calcium Transients in Bergmann Glial Cells J. Neurosci., April 11, 2007; 27(15): 4027 - 4035. [Abstract] [Full Text] [PDF]

				G. Burnstock Physiology and Pathophysiology of Purinergic Neurotransmission Physiol Rev, April 1, 2007; 87(2): 659 - 797. [Abstract] [Full Text] [PDF]

				M. Hirono and K. Obata {alpha}-Adrenoceptive Dual Modulation of Inhibitory GABAergic Inputs to Purkinje Cells in the Mouse Cerebellum J Neurophysiol, February 1, 2006; 95(2): 700 - 708. [Abstract] [Full Text] [PDF]

				D. A. Rusakov, F. Saitow, K. P. Lehre, and S. Konishi Modulation of Presynaptic Ca2+ Entry by AMPA Receptors at Individual GABAergic Synapses in the Cerebellum J. Neurosci., May 18, 2005; 25(20): 4930 - 4940. [Abstract] [Full Text] [PDF]

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