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LTP is accompanied by an enhanced local excitability of pyramidal neuron dendrites

Abstract

The propagation and integration of signals in the dendrites of pyramidal neurons is regulated, in part, by the distribution and biophysical properties of voltage-gated ion channels. It is thus possible that any modification of these channels in a specific part of the dendritic tree might locally alter these signaling processes. Using dendritic and somatic whole-cell recordings, combined with calcium imaging in rat hippocampal slices, we found that the induction of long-term potentiation (LTP) was accompanied by a local increase in dendritic excitability that was dependent on the activation of NMDA receptors. These changes favored the back-propagation of action potentials into this dendritic region with a subsequent boost in the Ca2+ influx. Dendritic cell-attached patch recordings revealed a hyperpolarized shift in the inactivation curve of transient, A-type K+ currents that can account for the enhanced excitability. These results suggest an important mechanism associated with LTP for shaping signal processing and controlling dendritic function.

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Figure 1: Theta-burst pairing (TBP) induced strong and pathway-specific LTP.
Figure 2: Profile of b-AP-induced Ca2+ signals along the main apical dendrite.
Figure 3: Increase in dendritic Ca2+ signals from b-APs after LTP induction.
Figure 4: LTP was accompanied by an increase in dendritic b-AP amplitude.
Figure 5: Distal dendritic b-APs and Ca2+ signals—LTP.
Figure 6: Distal dendritic b-APs and Ca2+ signals—LTP block.
Figure 7: Dendrite-attached patch recordings revealed an increase in synaptic input with LTP.
Figure 8: Hyperpolarized shift in steady-state inactivation of distal dendritic IA with LTP.

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Acknowledgements

We wish to acknowledge L. Schexnayder for early work on this project at Baylor and thank H. Miyakawa and M. Inoue for help with the project at the MBL. In addition, we thank X. Chen, R. Gray, M. Haque, M. Migliore, R. Chitwood, N. Poolos, A. Jeromin and M. Ginger for important contributions. Supported by grants from the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Mental Health (NIMH) (D.J.& J.M.), the Human Frontier Science Program (D.J.) and the Alexander von Humboldt Foundation (A.F.).

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Correspondence to Daniel Johnston.

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Frick, A., Magee, J. & Johnston, D. LTP is accompanied by an enhanced local excitability of pyramidal neuron dendrites. Nat Neurosci 7, 126–135 (2004). https://doi.org/10.1038/nn1178

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