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Nagele, J.

Publications and source records attributed to Nagele, J..

3 recordsLinked to original sources

bioRxiv2025

Depolarizing afterpotentials in rodent mEC layer II neurons vary gradually across all principal cell types

Principal cells in Layer II (LII) of the rodent medial entorhinal cortex (mEC) often discharge in short burst episodes, whose biophysical mechanism and biological function are not fully understood. As shown by in vitro recordings in rats and in vivo recordings in mice, action potentials of stellate cells (SCs) and pyramidal cells (PCs) in mEC LII can trigger depolarizing afterpotentials (DAPs) that facilitate spike doublets and burst firing. In vitro recordings in mice confirm these findings for SCs and two additional cell types intermediate between SCs and PCs but suggest that mouse PCs generate minute DAPs only. To better understand the diversity and physiology of the intermediate LII mEC cell types, we performed slice experiments in Long Evans rats of both sexes and analyzed the data using clustering techniques. The analysis suggests four distinct cell clusters, reminiscent of previous observations in mice. On purpose, DAP properties were not used for the cluster analysis so that they could be studied post-hoc in an unbiased manner. Our results show that characteristic features of DAPs and other physiological markers are broadly distributed within each cell class and vary gradually from cluster to cluster, forming a continuum of biophysical properties.

neuroscience↗

bioRxiv2024

Grid cells anticipate the animal's future movement

Grid cells in the rodent medial entorhinal cortex preferentially fire spikes when the animal is within certain regions of space. When experimental data are averaged over time, spatial firing fields become apparent. If these firing fields represented only the current position of the animal, a grid cells firing should not depend on whether the animal is running into or out of a firing field. Yet many grid cells are sensitive to the animals direction of motion relative to the firing-field center. Such apparent egocentric "inbound-outbound tuning" could be a sign of prospective encoding of future position, but it is unclear whether grid cells code ahead in space or in time. To investigate this question, we decided to undo the inbound-outbound modulation by shifting all spikes within a given firing field by a fixed distance in space or in time. For grid-cell data recorded in mice, optimizing in space requires a forward shift of around 2.5 cm, whereas optimizing in time yielded a forward shift of about 170 ms. In either case the firing-field sizes decrease. Minimizing just the field size yields somewhat smaller shifts (roughly 1.8 cm and around 115 ms ahead). Jointly optimizing along the temporal and spatial dimension reveals a continuum of flat inbound-outbound tuning curves and a shallow minimum for field sizes, located at about 2.3 cm and 35 ms. These findings call into question a purely spatial or purely temporal interpretation of grid-cell firing fields and inbound-outbound tuning.

neuroscience↗

bioRxiv2019

Spike afterpotentials shape the in-vivo burst activity of principal cells in medial entorhinal cortex

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, 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 stellate and pyramidal 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 inter-spike intervals (ISIs) were typically between five and fifteen milliseconds. The ISI distributions of Layer-II cells without DAPs peaked sharply at around four milliseconds 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 two-dimensional arenas (Latuske et al., 2015). No difference in the spatial coding properties of the grid cells across all three groups was discernible. Layer III neurons were only sparsely bursting and had no DAPs. As various mechanisms for modulating the ion-channels underlying DAPs exist, our results suggest that the temporal features of MEC activity can be altered while maintaining the cells spatial tuning characteristics. Significance StatementDepolarizing 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 inter-spike intervals 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 two-dimensional arenas demonstrate that grid cells within these three groups have rather similar spatial coding properties. We conclude that DAPs shape the temporal but not the spatial response characteristics of principal neurons in MEC. Author contributionsAll authors designed research. DEC, CF, and JN performed research and analyzed data (equal contribution). AVMH wrote and edited the paper with support from MS and the other authors.

neuroscience↗