Benjamin J. Clark

Origins of landmark encoding in the brain

The ability to perceive ones position and directional heading relative to landmarks is necessary for successful navigation within an environment. Recent studies have shown that the visual system dominantly controls the neural representations of directional heading and location when familiar visual cues are available, and several neural circuits, or streams, have been proposed to be crucial for visual information processing. Here, we summarize the evidence that the dorsal presubiculum (also known as the postsubiculum) is critically important for the direct transfer of visual landmark information to spatial signals within the limbic system.

Disruption of the head direction cell network impairs the parahippocampal grid cell signal

Are we heading in the right direction? Some neurons, called grid cells, discharge at multiple locations to form a regular pattern that represents the animals environment. These cells use information about the animals running speed and direction of movement to constantly update its location. The so-called head direction cells provide the direction-of-movement signal. Winter et al. recorded neuronal activity in awake behaving rats. When they disabled the input from the head direction cells, the grid cells lost their normal function. These findings provide experimental confirmation of theoretical predictions that grid cells will no longer exhibit their characteristic firing pattern when the head direction signal is disturbed. Science, this issue p. 870 Inactivating the anterior thalamic nuclei affects the firing properties of neurons that represent space in the brain. Navigation depends on multiple neural systems that encode the moment-to-moment changes in an animal’s direction and location in space. These include head direction (HD) cells representing the orientation of the head and grid cells that fire at multiple locations, forming a repeating hexagonal grid pattern. Computational models hypothesize that generation of the grid cell signal relies upon HD information that ascends to the hippocampal network via the anterior thalamic nuclei (ATN). We inactivated or lesioned the ATN and subsequently recorded single units in the entorhinal cortex and parasubiculum. ATN manipulation significantly disrupted grid and HD cell characteristics while sparing theta rhythmicity in these regions. These results indicate that the HD signal via the ATN is necessary for the generation and function of grid cell activity.

Interaction of egocentric and world-centered reference frames in the rat posterior parietal cortex.

Navigation requires coordination of egocentric and allocentric spatial reference frames and may involve vectorial computations relative to landmarks. Creation of a representation of target heading relative to landmarks could be accomplished from neurons that encode the conjunction of egocentric landmark bearings with allocentric head direction. Landmark vector representations could then be created by combining these cells with distance encoding cells. Landmark vector cells have been identified in rodent hippocampus. Given remembered vectors at goal locations, it would be possible to use such cells to compute trajectories to hidden goals. To look for the first stage in this process, we assessed parietal cortical neural activity as a function of egocentric cue light location and allocentric head direction in rats running a random sequence to light locations around a circular platform. We identified cells that exhibit the predicted egocentric-by-allocentric conjunctive characteristics and anticipate orienting toward the goal.

Vestibular and attractor network basis of the head direction cell signal in subcortical circuits

Accurate navigation depends on a network of neural systems that encode the moment-to-moment changes in an animals directional orientation and location in space. Within this navigation system are head direction (HD) cells, which fire persistently when an animals head is pointed in a particular direction (Sharp et al., 2001a; Taube, 2007). HD cells are widely thought to underlie an animals sense of spatial orientation, and research over the last 25+ years has revealed that this robust spatial signal is widely distributed across subcortical and cortical limbic areas. The purpose of the present review is to summarize some of the recent studies arguing that the origin of the HD signal resides subcortically, specifically within the reciprocal connections of the dorsal tegmental and lateral mammillary nuclei. Furthermore, we review recent work identifying “bursting” cellular activity in the HD cell circuit after lesions of the vestibular system, and relate these observations to the long held view that attractor network mechanisms underlie HD signal generation. Finally, we summarize anatomical and physiological work suggesting that this attractor network architecture may reside within the tegmento-mammillary circuit.

Both visual and idiothetic cues contribute to head direction cell stability during navigation along complex routes

Successful navigation requires a constantly updated neural representation of directional heading, which is conveyed by head direction (HD) cells. The HD signal is predominantly controlled by visual landmarks, but when familiar landmarks are unavailable, self-motion cues are able to control the HD signal via path integration. Previous studies of the relationship between HD cell activity and path integration have been limited to two or more arenas located in the same room, a drawback for interpretation because the same visual cues may have been perceptible across arenas. To address this issue, we tested the relationship between HD cell activity and path integration by recording HD cells while rats navigated within a 14-unit T-maze and in a multiroom maze that consisted of unique arenas that were located in different rooms but connected by a passageway. In the 14-unit T-maze, the HD signal remained relatively stable between the start and goal boxes, with the preferred firing directions usually shifting <45° during maze traversal. In the multiroom maze in light, the preferred firing directions also remained relatively constant between rooms, but with greater variability than in the 14-unit maze. In darkness, HD cell preferred firing directions showed marginally more variability between rooms than in the lighted condition. Overall, the results indicate that self-motion cues are capable of maintaining the HD cell signal in the absence of familiar visual cues, although there are limits to its accuracy. In addition, visual information, even when unfamiliar, can increase the precision of directional perception.

Movements of exploration intact in rats with hippocampal lesions

Prompted by the theoretical prediction that damage to the hippocampus should abolish exploratory behavior, the present study examined exploratory movements in control rats and rats with hippocampal lesions produced with the neurotoxin N-methyl d-aspartate (NMDA). In four daily 30-min sessions, control and hippocampal rats were exposed to an open circular table under room lighting. Both control and hippocampal rats spent a majority of time near, and organized trips away from, a portion of the table (home base) near a large cue placed proximal to the table. On Day 1, control and HPC rats made equal numbers of head orientations and a comparable number of trips, featuring equal travel distance and numbers of stops. By Day 4, dwell times near the home base increased and other movements decreased in the control rats but the activity profile of Day 1 persisted in the hippocampal rats. The high degree of similarity in behavior between hippocampal and control rats on Day 1 and the persistence of this behavior in hippocampal rats on Day 4 suggests that the hippocampus is not necessary for the display of normal exploratory movements per se. The absence of habituation of exploration in hippocampal rats is discussed in relation to contemporary theories of hippocampal function.

Intact Landmark Control and Angular Path Integration by Head Direction Cells in the Anterodorsal Thalamus After Lesions of the Medial Entorhinal Cortex

The medial entorhinal cortex (MEC) occupies a central position within neural circuits devoted to the representation of spatial location and orientation. The MEC contains cells that fire as a function of the animals head direction (HD), as well as grid cells that fire in multiple locations in an environment, forming a repeating hexagonal pattern. The MEC receives inputs from widespread areas of the cortical mantle including the ventral visual stream, which processes object recognition information, as well as information about visual landmarks. The role of the MEC in processing the HD signal or landmark information is unclear. We addressed this issue by neurotoxically damaging the MEC and recording HD cells within the anterodorsal thalamus (ADN). Direction‐specific activity was present in the ADN of all animals with MEC lesions. Moreover, the discharge characteristics of ADN HD cells were only mildly affected by MEC lesions, with HD cells exhibiting greater anticipation of future HDs. Tests of landmark control revealed that HD cells in lesioned rats were capable of accurately updating their preferred firing directions in relation to a salient visual cue. Furthermore, cells from lesioned animals maintained stable preferred firing directions when locomoting in darkness and demonstrated stable HD cell tuning when locomoting into a novel enclosure, suggesting that MEC lesions did not disrupt the integration of idiothetic cues, or angular path integration, by HD cells. Collectively, these findings suggest that the MEC plays a limited role in the formation and spatial updating of the HD cell signal.

Cortical connectivity maps reveal anatomically distinct areas in the parietal cortex of the rat.

A central feature of theories of spatial navigation involves the representation of spatial relationships between objects in complex environments. The parietal cortex has long been linked to the processing of spatial visual information and recent evidence from single unit recording in rodents suggests a role for this region in encoding egocentric and world-centered frames. The rat parietal cortex can be subdivided into four distinct rostral-caudal and medial-lateral regions, which includes a zone previously characterized as secondary visual cortex. At present, very little is known regarding the relative connectivity of these parietal subdivisions. Thus, we set out to map the connectivity of the entire anterior-posterior and medial-lateral span of this region. To do this we used anterograde and retrograde tracers in conjunction with open source neuronal segmentation and tracer detection tools to generate whole brain connectivity maps of parietal inputs and outputs. Our present results show that inputs to the parietal cortex varied significantly along the medial-lateral, but not the rostral-caudal axis. Specifically, retrosplenial connectivity is greater medially, but connectivity with visual cortex, though generally sparse, is more significant laterally. Finally, based on connection density, the connectivity between parietal cortex and hippocampus is indirect and likely achieved largely via dysgranular retrosplenial cortex. Thus, similar to primates, the parietal cortex of rats exhibits a difference in connectivity along the medial-lateral axis, which may represent functionally distinct areas.

Control of Anterodorsal Thalamic Head Direction Cells by Environmental Boundaries: Comparison With Conflicting Distal Landmarks

Experiments were conducted to determine whether environmental boundaries exert preferential control over the tuning of head direction (HD) cells. In each experiment, HD cells were recorded in the rat anterodorsal thalamus while they foraged for randomly scattered food in trapezoid‐ and rectangle‐shaped environments. After an initial recording session, each environment was rotated 90°, and changes in the preferred firing directions of HD cells were monitored. Rats were disoriented before each test session to prevent the use of self‐movement cues to maintain orientation from one session to the next. In Experiment 1, we demonstrate that HD cell tuning consistently shifted in register with the trapezoid shaped enclosure, but was more variable in the rectangle shaped environment. In Experiments 2 and 3, we show that the strong control by the trapezoid persists in the presence of one clearly visible distal landmark, but not when three or more distal landmarks, including view of the recording room, are present. Together, the results indicate that distinct environmental boundaries exert strong stimulus control over HD cell orientation. However, this geometric control can be overridden with a sufficient number of salient distal landmarks. These results stand in contrast to the view that information from geometric cues usually takes precedence over information from landmark cues.

Head direction cell activity in the anterodorsal thalamus requires intact supragenual nuclei

Neural activity in several limbic areas varies as a function of the animals head direction (HD) in the horizontal plane. Lesions of the vestibular periphery abolish this HD cell signal, suggesting an essential role for vestibular afference in HD signal generation. The organization of brain stem pathways conveying vestibular information to the HD circuit is poorly understood; however, recent anatomical work has identified the supragenual nucleus (SGN) as a putative relay. To test this hypothesis, we made lesions of the SGN in rats and screened for HD cells in the anterodorsal thalamus. In animals with complete bilateral lesions, the overall number of HD cells was significantly reduced relative to control animals. In animals with unilateral lesions of the SGN, directional activity was present, but the preferred firing directions of these cells were unstable and less influenced by the rotation of an environmental landmark. In addition, we found that preferred directions displayed large directional shifts when animals foraged for food in a darkened environment and when they were navigating from a familiar environment to a novel one, suggesting that the SGN plays a critical role in projecting essential self-motion (idiothetic) information to the HD cell circuit.