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Purinergic modulation of synaptic input to Purkinje neurons in rat cerebellar brain slices
Author(s) -
Brockhaus Johannes,
Dressel Diana,
Herold Sabine,
Deitmer Joachim W.
Publication year - 2004
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.0953-816x.2004.03325.x
Subject(s) - ppads , neuroscience , inhibitory postsynaptic potential , purinergic receptor , ionotropic effect , nbqx , cerebellar cortex , chemistry , postsynaptic potential , glutamate receptor , biophysics , biology , adenosine , cerebellum , receptor , ampa receptor , biochemistry
Adenosine triphosphate (ATP) is a cotransmitter and an extracellular neuromodulator in nervous systems, and it influences neural circuits and synaptic strength. We have studied a stimulating effect of ATP (100 µ m ) on the synaptic input of Purkinje neurons in acute cerebellar brain slices of juvenile rats (p14–19). Bath application of ATP increased the frequency of spontaneous postsynaptic currents (sPSCs) almost twofold, and increased their amplitude. These effects were fully suppressed by the P 2 receptor antagonist pyridoxalphosphate‐6‐azophenyl‐2′4′‐disulphonic acid (PPADS; 10 µ m ), or after blocking action potentials with tetrodotoxin (TTX; 0.5 µ m ), but were not impaired by inhibiting ionotropic, non‐NMDA glutamate receptors with 2,3‐dioxo‐6‐nitro‐1,2,3,4,‐tetrahydrobenzo[f]quinoxaline‐7‐sulphonamide (NBQX; 5 µ m ). The frequency of sPSCs was reduced by 35% by PPADS and increased by 50% after inhibiting ectonucleotidase with ARL67156 (50 µ m ), suggesting intrinsic, ‘tonic’, stimulation of synaptic activity via P 2 receptors. The pharmacological profile indicated that the ATP effect was mediated by both P 2 X and P 2 Y receptors, most probably of the P 2 X 5 – and P 2 Y 2,4 –like subtypes. The action potential frequency in the inhibitory basket cells was increased by 65%, and decreased in Purkinje neurons by 25%, in the presence of ATP. Our results suggest that ATP continuously modulates the cerebellar circuit by increasing the activity of inhibitory input to Purkinje neurons, and thus decreasing the main cerebellar output activity, which contributes to locomotor coordination.