Biophysical foundation and function of depolarizing afterpotentials in principal cells of the medial entorhinal cortex

Fischer, Caroline (2019): Biophysical foundation and function of depolarizing afterpotentials in principal cells of the medial entorhinal cortex. Dissertation, LMU München: Graduate School of Systemic Neurosciences (GSN)

Abstract

Neurons in layer II of the rodent medial entorhinal cortex (MEC) encode spatial information. One particular type, grid cells, tends to fire at specific spatial locations that form hexagonal lattices covering the explored environment. Within these firing fields grid cells frequently show short high-frequency spike sequences. Such bursts have received little attention but may contribute substantially to encoding spatial information. On the other hand, in vitro recordings of MEC principal cells have revealed that action potentials are followed by prominent depolarizing afterpotentials (DAP). Their biophysical foundation and function, however, are poorly understood. The objective of this study is to understand the mechanism behind the DAP by creating a biophysical realistic model of a stellate cell and to draw a connection between DAPs and burst firing in vivo. The developed single-compartment model reproduced the main electrophysi- ological characteristics of stellate cells in the MEC layer II, that are a DAP, sag, tonic firing in response to positive step currents and resonance. Using virtual blocking experiments, it was found that for the generation of the DAP only a NaP , KDR and leak current were necessary whereby the NaP current also exhibited a resurgent component. This suggests that for the generation of the DAP a balance between several currents is needed. In addition, the persistent and resurgent sodium current might play an important role. We analyzed the relevance of DAPs in vivo using whole-cell recordings of grid cells from Domnisoru et al. (2013). We found that around 20% of the cells exhibited a DAP. However, the percentage of cells was much lower than estimates from in vitro recordings. We showed that this is partly due to the quality of the recording as selecting APs from presumably good parts of the recording improved the visibility of DAPs. To investigate the relationship between DAPs and burst firing all cells were classified into bursty and non-bursty based on the spike-time autocorrelation. All cells with a DAP were bursty except the cell with the smallest DAP. Moreover, taking the mean of the spike-triggered average of the membrane potential for all bursty and non-bursty cells respectively showed a clear DAP for bursty but not for non-bursty cells. In summary, we found that the DAP can be realized in a single-compartment model by a NaP , KDR and leak current and provided evidence for the relevance of DAPs for burst firing in vivo.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: depolarizing afterpotential, medial entorhinal cortex, single-compartment model
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
• Fakultäten: Graduate School of Systemic Neurosciences (GSN)
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 27. Juni 2019
• 1. Bericht­erstatter:in: Herz, Andreas