PMID- 32332120 OWN - NLM STAT- MEDLINE DCOM- 20201022 LR - 20201207 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 40 IP - 23 DP - 2020 Jun 3 TI - Spike Afterpotentials Shape the In Vivo Burst Activity of Principal Cells in Medial Entorhinal Cortex. PG - 4512-4524 LID - 10.1523/JNEUROSCI.2569-19.2020 [doi] AB - Principal neurons in rodent medial entorhinal cortex (MEC) generate high-frequency bursts during natural behavior. While in vitro studies point to potential mechanisms that could support such burst sequences, it remains unclear whether these mechanisms are effective under in vivo conditions. In this study, we focused on the membrane-potential dynamics immediately following action potentials (APs), as measured in whole-cell recordings from male mice running in virtual corridors (Domnisoru et al., 2013). These afterpotentials consisted either of a hyperpolarization, an extended ramp-like shoulder, or a depolarization reminiscent of depolarizing afterpotentials (DAPs) recorded in vitro in MEC principal neurons. Next, we correlated the afterpotentials with the cells' propensity to fire bursts. All DAP cells with known location resided in Layer II, generated bursts, and their interspike intervals (ISIs) were typically between 5 and 15 ms. The ISI distributions of Layer-II cells without DAPs peaked sharply at around 4 ms and varied only minimally across that group. This dichotomy in burst behavior is explained by cell-group-specific DAP dynamics. The same two groups of bursting neurons also emerged when we clustered extracellular spike-train autocorrelations measured in real 2D arenas (Latuske et al., 2015). Apart from slight variations in grid spacing, no difference in the spatial coding properties of the grid cells across all three groups was discernible. Layer III neurons were only sparsely bursting (SB) and had no DAPs. As various mechanisms for modulating ion-channels underlying DAPs exist, our results suggest that temporal features of MEC activity can be altered while maintaining the cells' overall spatial tuning characteristics.SIGNIFICANCE STATEMENT Depolarizing afterpotentials (DAPs) are frequently observed in principal neurons from slice preparations of rodent medial entorhinal cortex (MEC), but their functional role in vivo is unknown. Analyzing whole-cell data from mice running on virtual tracks, we show that DAPs do occur during behavior. Cells with prominent DAPs are found in Layer II; their interspike intervals (ISIs) reflect DAP time-scales. In contrast, neither the rarely bursting cells in Layer III, nor the high-frequency bursters in Layer II, have a DAP. Extracellular recordings from mice exploring real 2D arenas demonstrate that grid cells within these three groups have similar spatial coding properties. We conclude that DAPs shape the temporal response characteristics of principal neurons in MEC with little effect on spatial properties. CI - Copyright (c) 2020 the authors. FAU - Csordas, Dora E AU - Csordas DE AD - Bernstein Center for Computational Neuroscience Munich and Faculty of Biology, Ludwig-Maximilians-Universitat Munchen, Martinsried-Planegg 82152, Germany. FAU - Fischer, Caroline AU - Fischer C AD - Bernstein Center for Computational Neuroscience Munich and Faculty of Biology, Ludwig-Maximilians-Universitat Munchen, Martinsried-Planegg 82152, Germany. FAU - Nagele, Johannes AU - Nagele J AD - Bernstein Center for Computational Neuroscience Munich and Faculty of Biology, Ludwig-Maximilians-Universitat Munchen, Martinsried-Planegg 82152, Germany. FAU - Stemmler, Martin AU - Stemmler M AUID- ORCID: 0000-0002-9040-0475 AD - Bernstein Center for Computational Neuroscience Munich and Faculty of Biology, Ludwig-Maximilians-Universitat Munchen, Martinsried-Planegg 82152, Germany. FAU - Herz, Andreas V M AU - Herz AVM AUID- ORCID: 0000-0002-3836-565X AD - Bernstein Center for Computational Neuroscience Munich and Faculty of Biology, Ludwig-Maximilians-Universitat Munchen, Martinsried-Planegg 82152, Germany herz@bio.lmu.de. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200424 PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 SB - IM MH - Action Potentials/*physiology MH - Animals MH - Entorhinal Cortex/*cytology/*physiology MH - Grid Cells/*physiology MH - Male MH - Membrane Potentials/physiology MH - Mice MH - Mice, Inbred C57BL MH - Principal Component Analysis/methods PMC - PMC7275867 OTO - NOTNLM OT - bursts OT - grid cells OT - medial entorhinal cortex OT - spatial navigation OT - spike afterpotentials OT - whole-cell recording in vivo EDAT- 2020/04/26 06:00 MHDA- 2020/10/23 06:00 PMCR- 2020/12/03 CRDT- 2020/04/26 06:00 PHST- 2019/10/28 00:00 [received] PHST- 2020/04/03 00:00 [revised] PHST- 2020/04/11 00:00 [accepted] PHST- 2020/04/26 06:00 [pubmed] PHST- 2020/10/23 06:00 [medline] PHST- 2020/04/26 06:00 [entrez] PHST- 2020/12/03 00:00 [pmc-release] AID - JNEUROSCI.2569-19.2020 [pii] AID - JN-RM-2569-19 [pii] AID - 10.1523/JNEUROSCI.2569-19.2020 [doi] PST - ppublish SO - J Neurosci. 2020 Jun 3;40(23):4512-4524. doi: 10.1523/JNEUROSCI.2569-19.2020. Epub 2020 Apr 24.