Order-Dependent Coincidence Detection in Cerebellar Purkinje Neurons at the Inositol Trisphosphate Receptor

By Dmitry Sarkisov, S. Wang. 2008

74 citations recorded by the source corpus.

Associative long-term depression (LTD) at cerebellar parallel fiber–Purkinje cell synapses is sensitive to the temporal order in which the parallel fiber is coactivated with the climbing fiber input, but how order sensitivity is achieved is unknown. Here we show that the cerebellar inositol-1,4,5-trisphosphate (IP3) receptor, whose activation is required for LTD induction, is sensitive in situ to the order of presentation of its coagonists, IP3 and cytoplasmic calcium. By focally photolyzing a novel caged IP3 compound in dendritic spines, we find that pairing IP3 with climbing fiber-mediated calcium entry leads to a large calcium release transient if the climbing fiber is activated up to 100 ms before or up to 500 ms after IP3 uncaging. This asymmetric timing window for coactivation follows the kinetics of calcium removal and IP3 unbinding from the receptor and is not limited by IP3 metabolism. IP3 receptor binding thus acts as an eligibility trace that can drive temporal order-dependent calcium release and LTD induction in Purkinje cells and event order-dependent sensory plasticity in the whole animal.

Subfields: Cell Biology, Cellular and Molecular Neuroscience, Neurology

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Citations in the corpus

Rare Neural Correlations Implement Robotic Conditioning with Delayed Rewards and Disturbances (2013, background): “An important topic in neural computation is the understanding tagging (Frey and Morris, 1997; Redondo and Morris, 2011 ) or eligibility traces (Wang et al., 2000; Sarkisov and Wang, 2008).”
Widespread State-Dependent Shifts in Cerebellar Activity in Locomoting Mice (2012, methodology): “Calcium transients were identified after highpass filtering PC dendritic fluorescence to remove variations on time scales longer than ,1 s and applying a filter that selected for the milliseconds-scale rise [49,50,51] and slower decline [15] of complex-spike-triggered calcium transients.”
The spike timing dependence of plasticity (2012, background): “Strong evidence suggests that the order-dependent coincidence detector is the IP3 receptor, which is coactivated by PLC-produced IP3 and VSCC-derived cytosolic calcium (Nakamura et al., 1999; Wang et al., 2000; Sarkisov and Wang, 2008).”
Burst timing-dependent plasticity of NMDA receptor-mediated transmission in midbrain dopamine neurons: A putative cellular substrate for reward learning (2009, unknown): “Indeed, IP3-mediated enhancement of Ca signals has been shown to last for hundreds of milliseconds because of prolonged lifetime of IP3 binding to IP3Rs (Sarkisov and Wang, 2008).”
Distinct dopamine receptor pathways underlie the temporal sensitivity of associative learning (2019, background): “In the cerebellum, bidirectional plasticity at parallel fiber-Purkinje neuron synapses has been proposed to similarly rely on calcium release from the ER lumen via IP3 receptors (Finch and Augustine, 1998; Sarkisov and Wang, 2008; Wang et al., 2000).”
Frontiers in Synaptic Neuroscience Synaptic Neuroscience (unknown): “Here, spike and synaptic activation could leave a time decaying eligibility trace (Wang et al., 2000; Sarkisov and Wang, 2008) that subsequent neuromodulator receptor activation may then interact with to modulate plasticity.”
Spike Timing Dependent Plasticity: A Consequence of More Fundamental Learning Rules (2010, unknown): “At cerebellar parallel fiber-Purkinje cell synapses timing-dependence of LTD (Wang et al., 2000a; Safo and Regehr, 2008) may arise from the properties of calcium release driven by the second messenger IP 3 (Sarkisov and Wang, 2008).”