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Somatodendritic integration under increased network activity in layer 5 pyramidal cells of the somatosensory cortex

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Abstract

Integrative properties of single neurons have been extensively studied in acute brain slices. However, these preparations are characterized by extremely low levels of synaptic and action potential activity. In comparison to in vivo, reduced intracortical input and lack of subcortical modulation increase the effective difference between mean membrane potential and spiking threshold, preventing self-sustained network activity in vitro. To elicit an increased and stable network activity (INA) in vitro comparable to that found in awake animals, we mimicked subcortical cholinergic and serotoninergic inputs using carbachol or barium alone or in combination with serotonin in layer 5 pyramidal cells in slices of mouse somatosensory cortex. INA is primarily induced by a modulation of intrinsic conductances resulting in a depolarization of the membrane potential. We studied the impact of INA on synaptic and somatodendritic integration using extracellular stimulation and dendritic calcium imaging. Synaptic inhibition is strengthened due to an increased driving force for chloride. The critical frequency at which somatic action potentials induce a dendritic calcium action potential is lowered. Simultaneous inhibitory synaptic input is powerful enough to suppress dendritic calcium action potential generation. Pharmacologically induced INA enables the study of neuronal integration in well-accessible cortical slices within an active network.

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Acknowledgements

We thank Drs. Alain Destexhe, Michele Giugliano, Serge Korogod, Matthew Larkum, and Hans-R. Lüscher for useful discussions and comments on earlier versions of the manuscript. This work was supported by the Swiss National Foundation (Grant 3100-107529/1) and the Novartis Foundation for Medical-Biological Research.

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  1. Institute of Physiology, University of Bern, Bühlplatz 5, 3012, Bern, Switzerland

    Florian B. Neubauer & Thomas Berger

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  1. Florian B. Neubauer
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  2. Thomas Berger
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Correspondence to Thomas Berger.

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Supplementary Fig. 1

Serotonin activates the persistent sodium current in layer 5 pyramidal cells. Somatic voltage—clamp recording of persistent sodium currents. The pipette solution contained (in mM): 120 CsOH, 5 CsCl, 20 TEA—acetate, 4 4—aminopyridine, 10 EGTA, 10 HEPES, 4 Mg—ATP, 0.3 Na2—GTP, 10 Na2—Phosphocreatine, pH adjusted to 7.3 with gluconic acid (50 % v/v in H2O). Under control conditions, potassium and calcium currents as well as Ih are blocked with Cs—gluconate, TEA, and 4—aminopyridine in the pipette solution and 100 μM NiCl2, 200 μM CdCl2, and 20 μM ZD7288 in the bath. A voltage command (upper panel) from a clamp potential Vc of —70 mV to 0 mV for 2 s results in the complete inactivation of the transient sodium current. A consecutive ramp voltage command from 0 mV to —70 mV within 2 s (slope —35 mV / s) activates the persistent current which can be seen as a slow downward deflection of the current trace (arrow; lower panel, black trace). The activation range for the persistent sodium current is 0 to —55 mV. Using the identical protocol following bath application of 20 μM serotonin results in an increased amplitude of the persistent sodium current (lower panel, gray trace). Mouse P13. (JPG 286 kb)

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Neubauer, F.B., Berger, T. Somatodendritic integration under increased network activity in layer 5 pyramidal cells of the somatosensory cortex. Pflugers Arch - Eur J Physiol 455, 1063–1079 (2008). https://doi.org/10.1007/s00424-007-0350-z

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