Head direction (HD) cells discharge based on an animal's directional heading. Computational models propose that a ring-attractor network across the connections between the lateral mammillary (LMN) and dorsal tegmental nuclei (DTN) underlies the signal's generation. These models contain neurons that encode either HD or angular head velocity (AHV), but also require cells that are sensitive to both parameters conjunctively (HD + AHV). Here we identify both types of HD cells in the LMN and DTN of female rats, with one population sensitive to AHV (both symmetric and asymmetric), and the other population insensitive to AHV. Notably, many HD + AHV cells are also sensitive to the animal's linear head-speed (LHS). In contrast, anterodorsal thalamic HD cells are rarely sensitive to AHV or LHS. These findings demonstrate that the requisite HD + AHV cell is present in areas that generate the HD signal and supports the view that a ring attractor network underlies its generation in mammals.

Head direction (HD) cells discharge as a function of the animal’s directional heading and are believed to underlie one’s sense of direction. They have been identified in several brain areas, although the signal is thought to be generated across the connections between the lateral mammillary (LMN) and dorsal tegmental nuclei (DTN). Computational models have proposed that a ring-attractor network underlies the mechanisms that generate the signal. These models usually contain separate populations of neurons that encode HD and angular head velocity (AHV). Currently, both cell types have been identified in the LMN and DTN. However, HD attractor models also require cells, referred to as ‘rotation’ cells, which are sensitive to both parameters conjunctively (HD+AHV). Here we sought to identify such cells in the LMN-DTN network. We identified two distinct types of HD cells. The majority of LMN HD cells (∼64%) were AHV-independent, responding only to the animal’s directional heading. However, a second population (∼36%) was sensitive to both HD and AHV. Both symmetric and asymmetric AHV cell types were found. Similar results were found in the DTN, but with a higher percentage of conjunctive HD+AHV cells (60%). Notably, many HD+AHV conjunctive cells were also sensitive to the animal’s linear velocity (LV). In contrast, HD cells in the anterodorsal thalamus were rarely sensitive to AHV or LV. These findings demonstrate that the requisite rotation-type HD cell is present in brain areas responsible for generating the HD signal and supports the view that an attractor style network underlies its generation in mammals. Statements and Declaratio This manuscript does not represent the official view of the National Institute of Neurological Disorders and Stroke (USA) (NINDS), the National Institutes of Health (USA) (NIH), or any part of the US Federal Government. No official support or endorsement of this article by the NINDS or NIH is intended or should be inferred. ### Competing Interest Statement The authors have declared no competing interest.

Rodent open field behavior is highly organized and occurs spontaneously in novel environments. This organization is disrupted in mice with vestibular pathology, suggesting vestibular signals provide important contributions to this behavior. A caveat to this interpretation is that previous studies have investigated open field behavior in adult mice with congenital vestibular dysfunction, and the observed deficits may have resulted from developmental changes instead of the lack of vestibular signals. To determine which aspects of open field behavior depend specifically on vestibular signals, mouse movement organization was examined under dark and light conditions at two time points, 1 and 2 months, after bilateral chemical labyrinthectomy. Our results show that acquired vestibular damage selectively disrupted the organization of open field behavior. Access to visual environmental cues attenuated, but did not eliminate, these significant group differences. Improvement in movement organization from the first to the second testing session was limited to progression path circuity. These observations provide evidence for the role of the vestibular system in maintaining spatial orientation and establishes a foundation to investigate neuroplasticity in brain systems that process self-movement information.

Spatial orientation is a ubiquitous feature of animal behavior. Environmental and self-movement cues are sources of information used to maintain spatial orientation. The literature has typically focused on differences between mice and rats using environmental cues to guide movement. The current study uses the organization of exploratory behavior under dark conditions to investigate species differences in self-movement cue processing. Mouse and rat exploratory behavior was recorded under dark conditions on a circular table without walls. The resulting movements were segmented in progressions (movement ≥ 3 cm/s) and stops (movement<3 cm/s). Mice exhibited longer travel distances, faster progression peak speeds, and weaker tendency to scale progression peak speeds to Euclidean distances relative to rats. In contrast, similar levels of performance were observed on measures (progression path circuity, change in heading, stability of stopping behavior) sensitive to vestibular pathology. These results are consistent with species differences in a variety of performance variables; however, self-movement cue based spatial orientation did not differentiate between mice and rats. This work establishes a translational foundation for future work investigating the neurobiology of self-movement cue processing using species-unique neuroscience techniques.

Nearly all species rely on visual and nonvisual cues to guide navigation, and which ones they use depend on the environment and task demands. The postsubiculum (PoS) is a crucial brain region for the use of visual cues, but its role in the use of self-movement cues is less clear. We therefore evaluated rats' navigational performance on a food-carrying task in light and in darkness in rats that had bilateral neurotoxic lesions of the PoS. Animals were trained postoperatively to exit a refuge and search for a food pellet, and carry it back to the refuge for consumption. In both light and darkness, control and PoS-lesioned rats made circuitous outward journeys as they searched for food. However, only control rats were able to accurately use visual or self-movement cues to make relatively direct returns to the home refuge. These results suggest the PoS's role in navigation is not limited to the use of visual cues, but also includes the use of self-movement cues. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The vestibular system provides a crucial component of place-cell and head-direction cell activity [1-7]. Otolith signals are necessary for head-direction signal stability and associated behavior [8, 9], and the head-direction signal's contribution to parahippocampal spatial representations [10-14] suggests that place cells may also require otolithic information. Here, we demonstrate that self-movement information from the otolith organs is necessary for the development of stable place fields within and across sessions. Place cells in otoconia-deficient tilted mice showed reduced spatial coherence and formed place fields that were located closer to environmental boundaries, relative to those of control mice. These differences reveal an important otolithic contribution to place-cell functioning and provide insight into the cognitive deficits associated with otolith dysfunction.

The limbic thalamus, specifically the anterior thalamic nuclei (ATN), contains brain signals including that of head direction cells, which fire as a function of an animal's directional orientation in an environment. Recent work has suggested that this directional orientation information stemming from the ATN contributes to the generation of hippocampal and parahippocampal spatial representations, and may contribute to the establishment of unique spatial representations in radially oriented tasks such as the radial arm maze. While previous studies have shown that ATN lesions can impair spatial working memory performance in the radial maze, little work has been done to investigate spatial reference memory in a discrimination task variant. Further, while previous studies have shown that ATN lesions can impair performance in the radial maze, these studies produced the ATN lesions prior to training. It is therefore unclear whether the ATN lesions disrupted acquisition or retention of radial maze performance. Here, we tested the role of ATN signaling in a previously learned spatial discrimination task on a radial arm maze. Rats were first trained to asymptotic levels in a task in which two maze arms were consistently baited across training. After 24 h, animals received muscimol inactivation of the ATN before a 4 trial probe test. We report impairments in post-inactivation trials, suggesting that signals from the ATN modulate the use of a previously acquired spatial discrimination in the radial-arm maze. The results are discussed in relation to the thalamo-cortical limbic circuits involved in spatial information processing, with an emphasis on the head direction signal.

The organization of rodent exploratory behavior appears to depend on self-movement cue processing. As of yet, however, no studies have directly examined the vestibular system's contribution to the organization of exploratory movement. The current study sequentially segmented open field behavior into progressions and stops in order to characterize differences in movement organization between control and otoconia-deficient tilted mice under conditions with and without access to visual cues. Under completely dark conditions, tilted mice exhibited similar distance traveled and stop times overall, but had significantly more circuitous progressions, larger changes in heading between progressions, and less stable clustering of home bases, relative to control mice. In light conditions, control and tilted mice were similar on all measures except for the change in heading between progressions. This pattern of results is consistent with otoconia-deficient tilted mice using visual cues to compensate for impaired self-movement cue processing. This work provides the first empirical evidence that signals from the otolithic organs mediate the organization of exploratory behavior, based on a novel assessment of spatial orientation.

Acetylcholine contributes to accurate performance on some navigational tasks, but details of its contribution to the underlying brain signals are not fully understood. The medial septal area provides widespread cholinergic input to various brain regions, but selective damage to medial septal cholinergic neurons generally has little effect on landmark-based navigation, or the underlying neural representations of location and directional heading in visual environments. In contrast, the loss of medial septal cholinergic neurons disrupts navigation based on path integration, but no studies have tested whether these path integration deficits are associated with disrupted head direction (HD) cell activity. Therefore, we evaluated HD cell responses to visual cue rotations in a familiar arena, and during navigation between familiar and novel arenas, after muscarinic receptor blockade with systemic atropine. Atropine treatment reduced the peak firing rate of HD cells, but failed to significantly affect other HD cell firing properties. Atropine also failed to significantly disrupt the dominant landmark control of the HD signal, even though we used a procedure that challenged this landmark control. In contrast, atropine disrupted HD cell stability during navigation between familiar and novel arenas, where path integration normally maintains a consistent HD cell signal across arenas. These results suggest that acetylcholine contributes to path integration, in part, by facilitating the use of idiothetic cues to maintain a consistent representation of directional heading.

The neural representation of directional heading is conveyed by head direction (HD) cells located in an ascending circuit that includes projections from the lateral mammillary nuclei (LMN) to the anterodorsal thalamus (ADN) to the postsubiculum (PoS). The PoS provides return projections to LMN and ADN and is responsible for the landmark control of HD cells in ADN. However, the functional role of the PoS projection to LMN has not been tested. The present study recorded HD cells from LMN after bilateral PoS lesions to determine whether the PoS provides landmark control to LMN HD cells. After the lesion and implantation of electrodes, HD cell activity was recorded while rats navigated within a cylindrical arena containing a single visual landmark or while they navigated between familiar and novel arenas of a dual-chamber apparatus. PoS lesions disrupted the landmark control of HD cells and also disrupted the stability of the preferred firing direction of the cells in darkness. Furthermore, PoS lesions impaired the stable HD cell representation maintained by path integration mechanisms when the rat walked between familiar and novel arenas. These results suggest that visual information first gains control of the HD cell signal in the LMN, presumably via the direct PoS → LMN projection. This visual landmark information then controls HD cells throughout the HD cell circuit.

Navigation and the underlying brain signals are influenced by various allothetic and idiothetic cues, depending on environmental conditions and task demands. Visual landmarks typically control navigation in familiar environments but, in the absence of landmarks, self-movement cues are able to guide navigation relatively accurately. These self-movement cues include signals from the vestibular system, and may originate in the semicircular canals or otolith organs. Here, we tested the otolithic contribution to navigation on a food-hoarding task in darkness and in light. The dark test prevented the use of visual cues and thus favored the use of self-movement information, whereas the light test allowed the use of both visual and non-visual cues. In darkness, tilted mice made shorter-duration stops during the outward journey, and made more circuitous homeward journeys than control mice; heading error, trip duration, and peak error were greater for tilted mice than for controls. In light, tilted mice also showed more circuitous homeward trips, but appeared to correct for errors during the journey; heading error, trip duration, and peak error were similar between groups. These results suggest that signals from the otolith organs are necessary for accurate homing performance in mice, with the greatest contribution in non-visual environments.

The vestibular system contributes to the performance of various spatial memory tasks, but few studies have attempted to disambiguate the roles of the semicircular canals and otolith organs in this performance. This study tested the otolithic contribution to spatial working and reference memory by evaluating the performance of otoconia-deficient tilted mice on a radial arm maze and a Barnes maze. One radial arm maze task provided both intramaze and extramaze cues, whereas the other task provided only extramaze cues. The Barnes maze task provided only extramaze cues. On the radial arm maze, tilted mice performed similar to control mice when intramaze cues were available, but committed more working and reference memory errors than control mice when only extramaze cues were available. On the Barnes maze task, control and tilted mice showed similar latency, distance, and errors during acquisition training. On the subsequent probe trial, both groups spent the greatest percentage of time in the goal quadrant, indicating they were able to use extramaze cues to guide their search. Overall, these results suggest signals originating in the otolith organs contribute to spatial memory, but are not necessary for all aspects of spatial performance.

Spatial learning and navigation depend on neural representations of location and direction within the environment. These representations, encoded by place cells and head direction (HD) cells, respectively, are dominantly controlled by visual cues, but require input from the vestibular system. Vestibular signals play an important role in forming spatial representations in both visual and non-visual environments, but the details of this vestibular contribution are not fully understood. Here, we review the role of the vestibular system in generating various spatial signals in rodents, focusing primarily on HD cells. We also examine the vestibular system's role in navigation and the possible pathways by which vestibular information is conveyed to higher navigation centers.