Interspike Intervals Reveal Functionally Distinct Cell Populations in the Medial Entorhinal Cortex

Abstract

The superficial layers of the medial entorhinal cortex (MEC) contain spatially selective neurons that are crucial for spatial navigation and memory. These highly specialized neurons include grid cells, border cells, head-direction cells, and irregular spatially selective cells. In addition, MEC neurons display a large variability in their spike patterns at a millisecond time scale. In this study, we analyzed spike trains of neurons in the MEC superficial layers of mice and found that these neurons can be classified into two groups based on their propensity to fire spike doublets at 125-250 Hz. The two groups, labeled "bursty" and "non-bursty" neurons, differed in their spike waveforms and interspike interval adaptation but displayed a similar mean firing rate. Grid cell spatial periodicity was more commonly observed in bursty than in non-bursty neurons. In contrast, most neurons with head-direction selectivity or those that fired at the border of the environment were non-bursty neurons. During theta oscillations, both bursty and non-bursty neurons fired preferentially near the end of the descending phase of the cycle, but the spikes of bursty neurons occurred at an earlier phase than those of non-bursty neurons. Finally, analysis of spike-time crosscorrelations between simultaneously recorded neurons suggested that the two cell classes are differentially coupled to fast-spiking interneurons: bursty neurons were twice as likely to have excitatory interactions with putative interneurons as non-bursty neurons. These results demonstrate that bursty and non-bursty neurons are differentially integrated in the MEC network and preferentially encode distinct spatial signals.

Grid and Nongrid Cells in Medial Entorhinal Cortex Represent Spatial Location and Environmental Features with Complementary Coding Schemes

“…Using these criteria, a large majority (~95 %) of mEC cells was classified as spatial (Figure 1A), including numerous cells which would previously have been identified as non-spatial (Figure S2C). The proportions of cells with specialized spatial firing patterns were comparable to previous reports (grid cells: 17.7 %; border cells: 9.3 %) (Kropff et al, 2015; Latuske et al, 2015; Tang et al, 2014; Zhang et al, 2013) (Figure S2D), but also included a substantial fraction of spatial cells (67.5 %) that lacked any grid or border pattern. We refer to the latter type as non-grid spatial cells (Figure 1B, C and Table S1) and confirmed that their spatial firing patterns did not arise from systematic variation in running speed.…”

“…For mEC recordings, classification has previously been performed by first calculating descriptive values for each cell class (grid score, border score, spatial information, HD mean resultant length) and by then comparing the values to those calculated from the shuffled data of all recorded mEC cells pooled together (Figure S2A) (Barry et al, 2012; Bjerknes et al, 2015; Boccara et al, 2010; Koenig et al, 2011; Kropff et al, 2015; Krupic et al, 2015; Langston et al, 2010; Latuske et al, 2015; Perez-Escobar et al, 2016; Stensola et al, 2012; Tang et al, 2014; Wills et al, 2010; Winter et al, 2015; Zhang et al, 2013). However, pooling shuffled data across all cells fails to account for the firing statistics of individual cells, most notably the relationship between a cell’s firing rate and its spatial information (Figure S2B) (Rolls et al, 1997).…”

Stability of medial entorhinal cortex representations over time

“…Many previous studies have identified a substantial subset of mEC cells as nonspatial (Kropff et al, ; Latuske et al, ; Tang et al, ; Tang et al, ; Zhang et al, ). In contrast, recent work utilizing more sophisticated classification criteria found that almost all mEC cells exhibit some degree of spatial firing (Diehl et al, ; Hardcastle, Maheswaranathan, et al, ).…”

Spatial representation in the hippocampal formation: a history

“…Including the entire entorhinal-hippocampal circuit A key objective for a more complete understanding of entorhinal-hippocampal function will be to determine how cell types with different functional correlates map onto the variety of morphological or neurochemical cell types and their unique connectivity patterns. Recent data suggest that, in layer II of MEC, both stellate and pyramidal cells can be grid cells, although stellate cells may comprise the majority of them 256,257,[272][273][274][275] . If so, are grid patterns created independently in these two cell classes, or does one of them inherit the grid from the other?…”