Action potential timing determines dendritic calcium during striatal up-states

作者：Kerr JND; Plenz D^*

来源：Journal of Neuroscience, 2004, 24(4): 877-885.

DOI：10.1523/JNEUROSCI.4475-03.2004

• action potential backpropagation
• spike timing
• calcium
• NMDA
• plasticity
• fura-2
• organotypic culture
• spiny projection neuron
• dendritic processing
• up-state
• down-state
• cortex
• striatum
• substantia nigra
• electrophysiology
• imaging

Up-states represent a key feature of synaptic integration in cortex and striatum that involves activation of many synaptic inputs. In the striatum, the sparse firing and tight control of action potential timing is in contrast to the large intracellular membrane potential depolarizations observed during the up-state. One hallmark of striatal spiny projection neurons is the delay to action potential generation in both up-states and suprathreshold depolarization by somatic current injection. By studying somatic and dendritic intracellular calcium ([Ca2+](i)) transients during spontaneous up-states in cortex-striatum-substantia nigra organotypic cultures, we show that the delay between up-state onset and action potential generation determines dendritic peak [Ca2+](i). Peak [Ca2+](i) from single action potentials reached maximum values when action potentials were close to up-state onset and sharply decayed to near subthreshold up-state [Ca2+] levels as a function of time (tau = 47 +/- 26 msec for tertiary dendrite). Similarly, a precisely timed action potential elicited during subthreshold up-states through somatic current injection established that the delay between up-state onset and action potential generation is the critical variable that controls peak [Ca2+](i). Blocking NMDA channels internally with high intracellular Mg2+ ([Mg2+](i)) (10 mM) abolished the dependency of peak [Ca2+](i) on action potential timing during spontaneous up-states. Finally, high [Mg2+](i) specifically blocked [Ca2+](i) transients that resulted from local NMDA application in conjunction with backpropagating action potentials. We conclude that precisely timed, single action potentials during striatal up-states control peak dendritic calcium levels. We suggest that this mechanism might play an important role in synaptic plasticity of the corticostriatal pathway.

• 出版日期2004-1-28