Comparison of head direction cell firing characteristics across thalamo-parahippocampal circuitry

Abstract

Head direction (HD) cells, which fire persistently when an animal's head is pointed in a particular direction, are widely thought to underlie an animal's sense of spatial orientation and have been identified in several limbic brain regions. Robust HD cell firing is observed throughout the thalamo-parahippocampal system, although recent studies report that parahippocampal HD cells exhibit distinct firing properties, including conjunctive aspects with other spatial parameters, which suggest they play a specialized role in spatial processing. Few studies, however, have quantified these apparent differences. Here, we performed a comparative assessment of HD cell firing characteristics across the anterior dorsal thalamus (ADN), postsubiculum (PoS), parasubiculum (PaS), medial entorhinal (MEC), and postrhinal (POR) cortices. We report that HD cells with a high degree of directional specificity were observed in all five brain regions, but ADN HD cells display greater sharpness and stability in their preferred directions, and greater anticipation of future headings compared to parahippocampal regions. Additional analysis indicated that POR HD cells were more coarsely modulated by other spatial parameters compared to PoS, PaS, and MEC. Finally, our analyses indicated that the sharpness of HD tuning decreased as a function of laminar position and conjunctive coding within the PoS, PaS, and MEC, with cells in the superficial layers along with conjunctive firing properties showing less robust directional tuning. The results are discussed in relation to theories of functional organization of HD cell tuning in thalamo-parahippocampal circuitry.

Keywords: anterior thalamus; border cell; egocentric bearing; egocentric distance; grid cell; head direction cell; navigation; parahippocampal; place cell; theta.

Figure 1.

A. Circuit diagram showing the principal connections (arrows) between the anterodorsal thalamus (ADN), postsubiculum (PoS), parasubiculum (PaS), medial entorhinal cortex (MEC), and postrhinal cortex (POR). B. Representative electrode tracks in Cresyl violet stained sections for each region. C. Ten HD cell tuning curve plots (firing rate x HD) are shown for each region. Cells were selected based on their mean vector length: the 5 largest and 5 lowest mean vector length values are shown. Peak firing rate (top) and mean vector length (bottom) are reported above each tuning curve. D. Heat maps for each region show the population of classified HD cell tuning curves sorted by preferred firing direction (bin with maximum peak firing rate). Rows show the individual tuning curve of a cell with binned firing rates normalized on a scale from 0 to 1. E. Angular difference (degrees) between the preferred firing directions of HD cells recorded on the same tetrode in the same recording session. F. Representative tuning curves of bidirectional HD cells are shown for each region. Peak firing rate (top), mean vector length (middle), and bidirectional index (bottom) are reported above each tuning curve.

Figure 2.

Histograms showing the cumulative proportion for basic firing characteristics of HD cells measured across anterodorsal thalamus (ADN), postsubiculum (PoS), parasubiculum (PaS), medial entorhinal cortex (MEC), and postrhinal cortex (POR). *p < 0.05; **p < 0.01; ***p < 0.001.

Figure 3.

Histograms showing the cumulative proportion for burst index measures for all HD cells (top), the burst index from HD cells with peak firing rates between 10 and 20Hz (middle), and coefficient of variation for HD cells (bottom). Anterodorsal thalamus (ADN), postsubiculum (PoS), parasubiculum (PaS), medial entorhinal cortex (MEC), and postrhinal cortex (POR). *p < 0.05 ***p < 0.01 ***p < 0.001.

Figure 4.

Proportion of each conjunctive subtype found in each region. HD x T: HD x Theta; HD x G: HD x Grid; HD x B: HD x Border; HD x P: HD x Place; HD x LV: HD x Linear velocity; HD x AV: HD x angular head velocity; HD x EB: HD x Egocentric bearing; HD x ED: HD x Egocentric Distance.

Figure 5.

Scatter plots showing the relationship between burst and theta indices of HD cells for each region. Trendline (black) and Pearson’s correlations (r) are shown for each plot. Anterodorsal thalamus (ADN), postsubiculum (PoS), parasubiculum (PaS), medial entorhinal cortex (MEC), and postrhinal cortex (POR).

Figure 6.

Examples of HD cells tuned to linear velocity. Each row displays one cell. Left column: HD cell tuning curve with Rayleigh value. Middle column: linear velocity tuning curve with Pearson’s correlation (r) and slope. Right column: AHV tuning curve. Labels for each plot are as shown for the cell in the top row. The location of each cell is denoted on the left. Two cells are shown for the ADN (rows 5 and 6). One cell increased its firing with increasing linear velocity (row 5), while the other cell decreased its firing with increasing linear velocity (row 6). None of the cells shown here were classified as sensitive to AHV.

Figure 7.

Examples of HD cells tuned to AHV. Each row displays one cell. Left column: HD cell tuning curve with Rayleigh value. Middle column: AHV tuning curve with Pearson’s correlation (r) and slope values for CW and CCW portions. Right column: Linear velocity tuning curve with Pearson’s correlation (r) and slope values. Labels for plots are shown for the cell in the bottom row. The cells in the top two rows were from ADN; the cell in the bottom row was from POR. Note that the ADN cell in the second row has an inverted AHV function. The POR cell in the bottom row was sensitive to both AHV and linear velocity.

Figure 8.

HD cell tuning curves based on different AHV ranges. A) Ranked ordered distribution of peak firing rate ratios based on the high AHV range (90 – 300°/s) to low AHV range (0 – 30°/s) for all HD cells in each of the five brain areas. Ratios generally ranged between 0.5 to 2.0 with smooth continuous distributions for each brain area. The dashed line in each plot represents a ratio of 1.0. B) HD tuning curves for three different AHV ranges (see legend) for the 6 cells shown in the PoS ranked-ordered plot in A by the red dots (numbered 1–6). C) Same as B except for ADN and cells numbered 7–12 in the ranked ordered plot for ADN in A. Note that even in cells that had high ratios (e.g., cells 5, 6, 11, 12), there was still significant direction specific firing at the low AHV range. Axis labels for each plot are shown in the top row for each column.

Figure 9.

Scatter plots showing raw data and the median (black horizontal line) for basic firing characteristics of pure (red circles) and conjunctive (blue circles) HD cells in each region. *p < 0.05; **p < 0.01; ***p < 0.001.

Figure 10.. PCA and Cluster Analyses.

A) PCA using 12 different parameters and displaying the three best components (PC-1, PC-2, PC-3). Each plot displays how much each parameter contributes to that component. The plot on the left shows the amount of variance accounted for by the first 5 components. B) Cluster analyses using three different PCA components. C) Same as B, but analyzed by brain area. D) Analyses using k-means clustering to determine the optimal number of distinct clusters the data could be divided into; top: k-means silhouette analysis, bottom: k-means elbow analysis. E) Three-dimensional scatter plots color-coded by brain area using left: Rayleigh r, peak firing rate, and theta index; middle: peak firing rate, theta index, and burst index; right: Rayleigh r, peak firing rate, and absolute value of linear velocity correlation. See text for more details.

Figure 11.

Polar HD cell tuning curves (firing rate x HD) are shown for each laminar region (Sup = layers II/III; Deep = layers IV/V). The first 5 cells that exceeded the median mean vector length for each laminar region are shown. Above each tuning curve is the peak firing rate (top) and mean vector length (bottom) for that cell.

Figure 12.

A. Scatter plots showing raw data and the median (red horizontal line) for basic firing characteristics of superficial (gray circles) and deep layer (black circles) parahippocampal HD cells. B. Bar graph showing the proportion of pure HD cells (black bars) per superficial and deep layers of each parahippocampal region. *p < 0.05; **p < 0.01; ***p < 0.001.

Figure 13.

Scatter plots showing the mean vector length (left) and directional firing range (right) of each MEC layer III HD cells plotted as a function of recording location relative to the dorsal border of MEC. Trendline (black) is shown for each plot.