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Action Potential Regulation of Arc Expression| old_uid | 12729 |
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| title | Action Potential Regulation of Arc Expression |
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| start_date | 2013/07/19 |
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| schedule | 11h30 |
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| online | no |
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| summary | The immediate-early gene Arc plays a key role in neuronal plasticity mechanisms underlying learning and memory. However, the exact relationship between neuronal activity and Arc expression has remained elusive. Here we used juxtacellular nanostimulation (Houweling & Brecht, 2008) to establish the relationship between action potential (AP) firing and Arc expression in single cortical pyramidal neurons in vivo.
We systematically varied the number and frequency of APs in single layer 2 pyramidal cells in barrel somatosensory cortex of Arc-dVenus transgenic mice and subsequently monitored fluorescence of the Arc reporter using confocal microscopy. Fluorescence was observed after firing as few as 25-200 APs depending on the rate of AP firing. For a given firing rate expression increased monotonically with increasing AP numbers and approached asymptotic levels after 500 APs. The relationship between neuronal activity and Arc expression displayed a strong AP frequency dependence such that spike trains at lower firing rates required larger numbers of APs to induce Arc expression and resulted in lower asymptotic levels. Control experiments showed that nanostimulation-induced Arc expression required action potentials and was not dependent on excitatory synaptic inputs. Additional experiments in which brief nanostimulation trials were applied at regular time intervals suggest that AP activity can be faithfully integrated over periods of time lasting up to tens of minutes.
Together, we demonstrate that Arc expression is tightly regulated by neuronal activity over a wide range of time scales, from seconds to minutes. Moreover, these results are the first to establish a quantitative transfer function between in vivo neuronal activity and gene expression, at the single cell level. |
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| responsibles | Deris |
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