The anterior thalamic head-direction signal is abolished by bilateral but not unilateral lesions of the lateral mammillary nucleus

Abstract

Head-direction (HD) cells are neurons that signal a rat's directional heading in the horizontal plane. Evidence suggests that the lateral mammillary nucleus (LMN) may play an important role in generating the HD signal. Here, we examined the role of LMN in the HD circuit by comparing the effects of unilateral and bilateral LMN lesions on the activity of HD cells in the anterodorsal thalamus (AD). HD cells were recorded from AD in freely behaving rats. In the middle of the recording session, the rat received either bilateral or unilateral lesions of LMN. Immediately after the lesion, we continued recording the same HD cell in AD that had been recorded before the lesion. Additional cells were recorded from lesioned animals for up to 3 weeks after the lesion. We found that bilateral lesions of LMN permanently abolish HD cells in AD. After bilateral lesions, AD exhibits unusual rhythmic oscillations and velocity-correlated spike activity. Unilateral lesions of LMN did not abolish HD cells in AD. After unilateral lesions, the firing properties of HD cells in AD become more similar to those of HD cells in the intact hemisphere of LMN. We discuss the implications of these findings for understanding the role of LMN in the HD circuit.

Fig. 1.

Connections of the rat HD circuit (shading indicates regions that are known to contain HD cells).

Fig. 2.

HD cells in AD did not lose their directional firing properties in response to ULs of LMN. The directional tuning curves of each HD cell are plotted before (solid lines) and immediately after (broken lines) the UL. Notice that some HD cells reduced their firing rate, broadened their tuning width, or shifted their preferred firing direction immediately after ULs.Gray shading indicates the extent of the lesion in each case, at coordinates 4.52 (top) and 4.80 (bottom) mm posterior to bregma. Anatomical diagrams are adapted from the atlas of Paxinos and Watson (1997). SuM, Supramammillary nucleus; ML, medial mammillary nucleus (lateral division); MM, medial mammillary nucleus (medial division); Arc, arcuate hypothalamic nucleus.

Fig. 3.

HD cells remained present in AD for up to 2 weeks after ULs of LMN. The postlesion time interval is denoted at thetop of each graph. Notice that, in cases UL2 and UL5, the original HD cell that was recorded before the lesion (Fig. 2) apparently had recovered its firing properties after a few days (see Results).

Fig. 4.

HD cells in AD lost all of their directional firing properties in response to BLs of LMN. The directional tuning curves of each HD cell are plotted before (solid lines) and immediately after (broken lines) the BLs. Notice that HD cells did not fall silent after BLs but fired spontaneously in a nondirectional manner (see Results). Gray shading indicates the extent of the lesion in each case, as in Figure 2. PMD, Dorsal premammillary nucleus;LH, lateral hypothalamic area; PMV, ventral premammillary area; VTA, ventral tegmental area;SuM, supramammillary nucleus; ML, medial mammillary nucleus (lateral division); MM, medial mammillary nucleus (medial division); Arc, arcuate hypothalamic nucleus.

Fig. 5.

In four of six cases, the activity of former HD cells was correlated with the rat’s movement speed immediately after BLs. Graph plots the firing rate of former HD cells (y-axis) as a function of the rat’s movement speed (x-axis). The correlation was negative in case BL1, and positive in cases BL2, BL3, and BL6. See Results for regression analysis.

Fig. 6.

Emergence of rhythmic activity in AD after BLs, at sites in which HD cell activity was recorded before the lesions. Graphs show autocorrelation histograms for cell firing at different postlesion time intervals (only the positive half of the autocorrelation function is plotted). Histograms demonstrate little evidence for rhythmic activity immediately after the BL (left panels), but rhythmic firing at a frequency of 6 Hz begins to appear after 6 hr (middle panels) and becomes quite pronounced at longer delays (right panels). In case BL3, multiunit bursting appeared after 24 hr, so it was not possible to isolate single units. However, voltage traces show that, like single-unit activity, this multiunit bursting was synchronized to a frequency of ∼6 Hz (top right panel; 4 sec of voltage data are shown in four consecutive sweeps of 1 sec each).

Fig. 7.

HD cells in AD did not lose their directional firing properties in response to CTL lesions of LMN. CTL lesions only destroyed tissue surrounding LMN but not LMN itself (except in case CTL4 in which LMN was damaged on the right side but not the left side).Gray shading indicates the extent of the lesion in each case, at coordinates relative to bregma shown in boldbeside each section (Paxinos and Watson, 1997).

Fig. 8.

Mean directional information content before (PRE LESION), immediately after [POST (immediate)], and several days after [POST (delayed)] LMN lesions. Note that BLs completely eliminated all directional information content, but HD cells remain directional after UL and CTL lesions. There is no postdelayed condition for BL or CTL lesions, because HD cells were never again encountered after BLs, and searching for additional cells was not conducted after CTL lesions.