Head Direction Signal Research Articles

Electrophysiological signatures of veridical head direction in humans.

Information about heading direction is critical for navigation as it provides the means to orient ourselves in space. However, given that veridical head-direction signals require physical rotation of the head and most human neuroimaging experiments depend upon fixing the head in position, little is known about how the human brain is tuned to such heading signals. Here we adress this by asking 52 healthy participants undergoing simultaneous electroencephalography and motion tracking recordings (split into two experiments) and 10 patients undergoing simultaneous intracranial electroencephalography and motion tracking recordings to complete a series of orientation tasks in which they made physical head rotations to target positions. We then used a series of forward encoding models and linear mixed-effects models to isolate electrophysiological activity that was specifically tuned to heading direction. We identified a robust posterior central signature that predicts changes in veridical head orientation after regressing out confounds including sensory input and muscular activity. Both source localization and intracranial analysis implicated the medial temporal lobe as the origin of this effect. Subsequent analyses disentangled head-direction signatures from signals relating to head rotation and those reflecting location-specific effects. Lastly, when directly comparing head direction and eye-gaze-related tuning, we found that the brain maintains both codes while actively navigating, with stronger tuning to head direction in the medial temporal lobe. Together, these results reveal a taxonomy of population-level head-direction signals within the human brain that is reminiscent of those reported in the single units of rodents.

Transforming a head direction signal into a goal-oriented steering command.

To navigate, we must continuously estimate the direction we are headed in, and we must correct deviations from our goal1. Direction estimation is accomplished by ring attractor networks in the head direction system2,3. However, we do not fully understand how the sense of direction is used to guide action. Drosophila connectome analyses4,5 reveal three cell populations (PFL3R, PFL3L and PFL2) that connect the head direction system to the locomotor system. Here we use imaging, electrophysiology and chemogenetic stimulation during navigation to show how these populations function. Each population receives a shifted copy of the head direction vector, such that their three reference frames are shifted approximately 120° relative to each other. Each cell type then compares its own head direction vector with a common goal vector; specifically, it evaluates the congruence of these vectors via a nonlinear transformation. The output of all three cell populations is then combined to generate locomotor commands. PFL3R cells are recruited when the fly is oriented to the left of its goal, and their activity drives rightward turning; the reverse is true for PFL3L. Meanwhile, PFL2 cells increase steering speed, and are recruited when the fly is oriented far from its goal. PFL2 cells adaptively increase the strength of steering as directional error increases, effectively managing the tradeoff between speed and accuracy. Together, our results show how a map of space in the brain can be combined with an internal goal to generate action commands, via a transformation from world-centric coordinates to body-centric coordinates.

The Anterior Thalamus Preferentially Drives Allocentric But Not Egocentric Orientation Tuning in Postrhinal Cortex.

Navigating a complex world requires integration of multiple spatial reference frames, including information about one's orientation in both allocentric and egocentric coordinates. Combining these two information sources can provide additional information about one's spatial location. Previous studies have demonstrated that both egocentric and allocentric spatial signals are reflected by the firing of neurons in the rat postrhinal cortex (POR), an area that may serve as a hub for integrating allocentric head direction (HD) cell information with egocentric information from center-bearing and center-distance cells. However, we have also demonstrated that POR HD cells are uniquely influenced by the visual properties and locations of visual landmarks, bringing into question whether the POR HD signal is truly allocentric as opposed to simply being a response to visual stimuli. To investigate this issue, we recorded HD cells from the POR of female rats while bilaterally inactivating the anterior thalamus (ATN), a region critical for expression of the "classic" HD signal in cortical areas. We found that ATN inactivation led to a significant decrease in both firing rate and tuning strength for POR HD cells, as well as a disruption in the encoding of allocentric location by conjunctive HD/egocentric cells. In contrast, POR egocentric cells without HD tuning were largely unaffected in a consistent manner by ATN inactivation. These results indicate that the POR HD signal originates at least partially from projections from the ATN and supports the view that the POR acts as a hub for the integration of egocentric and allocentric spatial representations.

Angular Head Velocity Cells within Brainstem Nuclei Projecting to the Head Direction Circuit.

The sense of orientation of an animal is derived from the head direction (HD) system found in several limbic structures and depends on an intact vestibular labyrinth. However, how the vestibular system influences the generation and updating of the HD signal remains poorly understood. Anatomical and lesion studies point toward three key brainstem nuclei as key components for generating the HD signal-nucleus prepositus hypoglossi, supragenual nucleus, and dorsal paragigantocellularis reticular nuclei. Collectively, these nuclei are situated between the vestibular nuclei and the dorsal tegmental and lateral mammillary nuclei, which are thought to serve as the origin of the HD signal. To determine the types of information these brain areas convey to the HD network, we recorded neurons from these regions while female rats actively foraged in a cylindrical enclosure or were restrained and rotated passively. During foraging, a large subset of cells in all three nuclei exhibited activity that correlated with the angular head velocity (AHV) of the rat. Two fundamental types of AHV cells were observed; (1) symmetrical AHV cells increased or decreased their firing with increases in AHV regardless of the direction of rotation, and (2) asymmetrical AHV cells responded differentially to clockwise and counterclockwise head rotations. When rats were passively rotated, some AHV cells remained sensitive to AHV, whereas firing was attenuated in other cells. In addition, a large number of AHV cells were modulated by linear head velocity. These results indicate the types of information conveyed from the vestibular nuclei that are responsible for generating the HD signal.SIGNIFICANCE STATEMENT Extracellular recording of brainstem nuclei (nucleus prepositus hypoglossi, supragenual nucleus, and dorsal paragigantocellularis reticular nucleus) that project to the head direction circuit identified different types of AHV cells while rats freely foraged in a cylindrical environment. The firing of many cells was also modulated by linear velocity. When rats were restrained and passively rotated, some cells remained sensitive to AHV, whereas others had attenuated firing. These brainstem nuclei provide critical information about the rotational movement of the head of the rat in the azimuthal plane.

Cerebellar control of a unitary head direction sense

The head-direction (HD) system, a key neural circuit for navigation, consists of several anatomical structures containing neurons selective to the animal's head direction. HD cells exhibit ubiquitous temporal coordination across brain regions, independently of the animal's behavioral state or sensory inputs. Such temporal coordination mediates a single, stable, and persistent HD signal, which is essential for intact orientation. However, the mechanistic processes behind the temporal organization of HD cells are unknown. By manipulating the cerebellum, we identify pairs of HD cells recorded from two brain structures (anterodorsal thalamus and retrosplenial cortex) that lose their temporal coordination, specifically during the removal of the external sensory inputs. Further, we identify distinct cerebellar mechanisms that participate in the spatial stability of the HD signal depending on sensory signals. We show that while cerebellar protein phosphatase 2B-dependent mechanisms facilitate the anchoring of the HD signal on the external cues, the cerebellar protein kinase C-dependent mechanisms are required for the stability of the HD signal by self-motion cues. These results indicate that the cerebellum contributes to the preservation of a single and stable sense of direction.

A model for transforming egocentric views into goal-directed behavior.

Neurons in the rat postrhinal cortex (POR) respond to the egocentric (observer-centered) bearing and distance of the boundaries, or geometric center, of an enclosed space. Understanding of the precise geometric and sensory properties of the environment that generate these signals is limited. Here we model how this signal may relate to visual perception of motion parallax along environmental boundaries. A behavioral extension of this tuning is the known 'centering response', in which animals follow a spatial gradient function based on boundary parallax to guide behavior toward the center of a corridor or enclosure. Adding an allocentric head direction signal to this representation can translate the gradient across two-dimensional space and provide a new gradient for directing behavior to any location. We propose a model for how this signal may support goal-directed navigation via projections to the dorsomedial striatum. The result is a straightforward code for navigational variables derived from visual geometric properties of the surrounding environment, which may be used to map space and transform incoming sensory information into an appropriate motor output.

A Spiking Neural Network Model of Rodent Head Direction Calibrated With Landmark Free Learning.

Maintaining a stable estimate of head direction requires both self-motion (idiothetic) information and environmental (allothetic) anchoring. In unfamiliar or dark environments idiothetic drive can maintain a rough estimate of heading but is subject to inaccuracy, visual information is required to stabilize the head direction estimate. When learning to associate visual scenes with head angle, animals do not have access to the ‘ground truth' of their head direction, and must use egocentrically derived imprecise head direction estimates. We use both discriminative and generative methods of visual processing to learn these associations without extracting explicit landmarks from a natural visual scene, finding all are sufficiently capable at providing a corrective signal. Further, we present a spiking continuous attractor model of head direction (SNN), which when driven by idiothetic input is subject to drift. We show that head direction predictions made by the chosen model-free visual learning algorithms can correct for drift, even when trained on a small training set of estimated head angles self-generated by the SNN. We validate this model against experimental work by reproducing cue rotation experiments which demonstrate visual control of the head direction signal.

Head direction cells in a migratory bird prefer north.

Animals exhibit remarkable navigation abilities as if they have an internal compass. Head direction (HD) cells encoding the animal’s heading azimuth are found in the brain of several animal species; the HD cell signals are dependent on the vestibular nuclei, where magnetic responsive cells are present in birds. However, it is difficult to determine whether HD cell signals drive the compass orientation in animals, as they do not necessarily rely on the magnetic compass under all circumstances. Recording of HD cell activities from the medial pallium of shearwater chicks (Calonectris leucomelas) just before their first migration, during which they strongly rely on compass orientation, revealed that shearwater HD cells prefer a north orientation. The preference remained stable regardless of geolocations and environmental cues, suggesting the existence of a magnetic compass regulated by internally generated HD signals. Our findings provide insight into the integration of the direction and magnetoreception senses.

Landmark-modulated directional coding in postrhinal cortex.

Visual landmarks can anchor an animal’s internal sense of orientation to the external world. The rodent postrhinal cortex (POR) may facilitate this processing. Here, we demonstrate that, in contrast to classic head direction (HD) cells, which have a single preferred orientation, POR HD cells develop a second preferred orientation when an established landmark cue is duplicated along another environmental wall. We therefore refer to these cells as landmark-modulated–HD (LM-HD) cells. LM-HD cells discriminate between landmarks in familiar and novel locations, discriminate between visually disparate landmarks, and continue to respond to the previous location of a familiar landmark following its removal. Rats initially exposed to different stable landmark configurations show LM-HD tuning that may reflect the integration of visual landmark information into an allocentric HD signal. These results provide insight into how visual landmarks are integrated into a framework that supports the neural encoding of landmark-based orientation.

A model of head direction and landmark coding in complex environments.

Environmental information is required to stabilize estimates of head direction (HD) based on angular path integration. However, it is unclear how this happens in real-world (visually complex) environments. We present a computational model of how visual feedback can stabilize HD information in environments that contain multiple cues of varying stability and directional specificity. We show how combinations of feature-specific visual inputs can generate a stable unimodal landmark bearing signal, even in the presence of multiple cues and ambiguous directional specificity. This signal is associated with the retrosplenial HD signal (inherited from thalamic HD cells) and conveys feedback to the subcortical HD circuitry. The model predicts neurons with a unimodal encoding of the egocentric orientation of the array of landmarks, rather than any one particular landmark. The relationship between these abstract landmark bearing neurons and head direction cells is reminiscent of the relationship between place cells and grid cells. Their unimodal encoding is formed from visual inputs via a modified version of Oja's Subspace Algorithm. The rule allows the landmark bearing signal to disconnect from directionally unstable or ephemeral cues, incorporate newly added stable cues, support orientation across many different environments (high memory capacity), and is consistent with recent empirical findings on bidirectional HD firing reported in the retrosplenial cortex. Our account of visual feedback for HD stabilization provides a novel perspective on neural mechanisms of spatial navigation within richer sensory environments, and makes experimentally testable predictions.

Disruption of the anterior thalamic head direction signal following reduction of the hippocampal theta rhythm.

There is overlap between the structures containing head direction (HD) cells and those mediating the hippocampal theta rhythm, and both signals are thought to play an important role in spatial navigation. Previous research has shown that reversible inactivation of the medial septum attenuates hippocampal theta activity and disrupts path integration-based navigation. Although the HD signal reflects navigational performance, it is unclear whether theta rhythm contributes to the direction-specific activity of HD cells. We sought to determine whether HD cell activity is changed following reversible inactivation of the medial septum to eliminate theta rhythm. HD cells were recorded from the anterodorsal thalamus of female Long-Evans rats while they navigated in a cylindrical environment across standard, landmark rotation, and dark conditions. Following infusions of muscimol into the medial septum, recordings demonstrated a clear decrease in the power of hippocampal theta oscillations. In the landmark rotation experiment, intraseptal administration of muscimol produced HD cells with preferred directions that shifted unpredictably between sessions, suggesting that cue control was affected. Further, following septal inactivation many HD cells were unable to maintain a stable preferred firing direction within the recording sessions when the animals locomoted in the dark, suggesting that idiothetic processing was affected. These findings provide evidence that theta oscillations contribute to the directional stability of HD cells in anterodorsal thalamus. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A Thalamic Reticular Circuit for Head Direction Cell Tuning and Spatial Navigation

As we navigate in space, external landmarks and internal information guide our movement. Circuit and synaptic mechanisms that integrate these cues with head-direction (HD) signals remain, however, unclear. We identify an excitatory synaptic projection from the presubiculum (PreS) and the multisensory-associative retrosplenial cortex (RSC) to the anterodorsal thalamic reticular nucleus (TRN), so far classically implied in gating sensory information flow. Invitro, projections to TRN involve AMPA/NMDA-type glutamate receptors that initiate TRN cell burst discharge and feedforward inhibition of anterior thalamic nuclei. Invivo, chemogenetic anterodorsal TRN inhibition modulates PreS/RSC-induced anterior thalamic firing dynamics, broadens the tuning of thalamic HD cells, and leads to preferential use of allo- over egocentric search strategies in the Morris water maze. TRN-dependent thalamic inhibition is thus an integral part of limbic navigational circuits wherein it coordinates external sensory and internal HD signals to regulate the choice of search strategies during spatial navigation.

Precise coupling of the thalamic head-direction system to hippocampal ripples

The anterior thalamus is a key relay of neuronal signals within the limbic system. During sleep, the occurrence of hippocampal sharp wave-ripples (SWRs), believed to mediate consolidation of explicit memories, is modulated by thalamocortical network activity, yet how information is routed around SWRs and how this communication depends on neuronal dynamics remains unclear. Here, by simultaneously recording ensembles of neurons in the anterior thalamus and local field potentials in the CA1 area of the hippocampus, we show that the head-direction (HD) cells of the anterodorsal nucleus are set in stable directions immediately before SWRs. This response contrasts with other thalamic cells that exhibit diverse couplings to the hippocampus related to their intrinsic dynamics but independent of their anatomical location. Thus, our data suggest a specific and homogeneous contribution of the HD signal to hippocampal activity and a diverse and cell-specific coupling of non-HD neurons.

Experience- and Context-Dependent Modulation of the Invertebrate Compass System

How are head direction signals computed and maintained in neural circuits? In this issue of Neuron, Shiozaki etal. (2020) expand our understanding of the fly "compass" network, revealing context- and experience-dependent changes in the multiplexed encoding of head direction and steering maneuvers.

Vision and Locomotion Combine to Drive Path Integration Sequences in Mouse Retrosplenial Cortex.

The retrosplenial cortex (RSC) is involved in a broad range of cognitive functions, integrating rich sensory, motor, and spatial signals from multiple brain areas, including the hippocampal system. RSC neurons show hippocampus-dependent activity reminiscent of place cell sequences. Using cellular calcium imaging in a virtual reality (VR)-based locomotion task, we investigate how the integration of visual and locomotor inputs may give rise to such activity in RSC. A substantial population shows neural sequences that track position in the VR environment. This activity is driven by the conjunction of visual stimuli sequences and active movement, which is suggestive of path integration. The activity is anchored to a reference point and predominantly follows the VR upon manipulations of optic flow against locomotion. Thus, locomotion-gated optic flow, combined with the presence of contextual cues at the start of each trial, is sufficient to drive the sequential activity. A subpopulation shows landmark-related visual responses that are modulated by animal's position in the VR. Thus, rather than fragmenting the spatial representationinto equivalent locomotion-based ensemble versus optic-flow-based ensemble, in RSC, optic flow appears to override locomotion signals coherently in the population, when the gain betweenthe two signals is altered.

Home, head direction stability, and grid cell distortion.

The home is a unique location in the life of humans and animals. In rats, home presents itself as a multicompartmental space that involves integrating navigation through subspaces. Here we embedded the laboratory rat’s home cage in the arena, while recording neurons in the animal’s parasubiculum and medial entorhinal cortex, two brain areas encoding the animal’s location and head direction. We found that head direction signals were unaffected by home cage presence or translocation. Head direction cells remain globally stable and have similar properties inside and outside the embedded home. We did not observe egocentric bearing encoding of the home cage. However, grid cells were distorted in the presence of the home cage. While they did not globally remap, single firing fields were translocated toward the home. These effects appeared to be geometrical in nature rather than a home-specific distortion and were not dependent on explicit behavioral use of the home cage during a hoarding task. Our work suggests that medial entorhinal cortex and parasubiculum do not remap after embedding the home, but local changes in grid cell activity overrepresent the embedded space location and might contribute to navigation in complex environments.NEW & NOTEWORTHY Neural findings in the field of spatial navigation come mostly from an abstract approach that separates the animal from even a minimally biological context. In this article we embed the home cage of the rat in the environment to address some of the complexities of natural navigation. We find no explicit home cage representation. While both head direction cells and grid cells remain globally stable, we find that embedded spaces locally distort grid cells.

Multiple head direction signals within entorhinal cortex: origin and function.

Sensory systems show hierarchical computation, starting from primary sensory receptors, with information transformed into multimodal representations as they move through subcortical and cortical brain regions. Here, we discuss recent evidence illustrating that the signaling of direction within the mammalian brain is likewise transformed and multiplexed as it progresses from subcortical regions that contain tightly direction-coupled neurons through thalamus to regions that support navigation, such as the subiculum, entorhinal cortex and hippocampus. Such transformations in the directional signal as it ascends from thalamus to higher-order regions may allow the directional system to support a repertoire of behaviors that go beyond an animal orienting in space.

Lesions to the lateral mammillary nuclei disrupt spatial learning in rats.

The head direction (HD) signal is thought to originate in the reciprocal connections between the dorsal tegmental nuclei (DTN) and the lateral mammillary nuclei (LMN) and lesions to these structures disrupt the HD signal in downstream structures. Lesions to the DTN also disrupt performance on spatial tasks where directional heading is thought to be important. In Experiment 1, rats with bilateral electrolytic lesions of the LMN and sham controls were trained on 2 tasks previously shown to be sensitive to DTN damage. Rats were first trained on either a direction or rotation problem in a water T maze. LMN-lesioned rats were impaired relative to sham controls, on both the first block of 8 trials and on the total number of trials taken to reach criterion. In the food-foraging task, rats were trained to leave a home cage at the periphery of a circular table, find food in a food cup at the center of the table, and return to the home cage. Again, LMN-lesioned rats were impaired relative to sham rats, making more errors on the return component of the foraging trip. In Experiment 2, rats with electrolytic LMN lesions were also impaired on a dry land version of the direction and rotation problems and had difficulty discriminating between reinforced and nonreinforced locations on a 12-arm maze. These results build on previous behavioral and cell-recording studies and demonstrate the importance of the direction system to spatial learning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

A Thalamic Reticular Circuit for Head Direction Cell Tuning and Spatial Navigation

To navigate in space, an animal must reference external sensory landmarks to the spatial orientation of its body and head. Circuit and synaptic mechanisms that integrate external cues with internal head-direction (HD) signals to drive navigational behavior remain, however, poorly described. We identify an excitatory synaptic projection from the presubiculum and retrosplenial cortex to the anterodorsalmost sector of the thalamic reticular nucleus (TRN), so far classically implied in gating sensory information flow. Projections to TRN showed driver characteristics and involved AMPA/NMDA-type glutamate receptors that initiated TRN cell burst discharge and feedforward inhibition of anterior thalamic nuclei, where HD-tuned cells relevant for egocentric navigation reside. Chemogenetic anterodorsal TRN inhibition broadened the tuning of thalamic HD cells and compromised egocentric search strategies in the Morris water maze. Besides sensory gating, TRN-dependent thalamic inhibition is an integral part of limbic navigational circuits to recruit HD-cell-dependent search strategies during spatial navigation.

Functional and anatomical relationships between the medial precentral cortex, dorsal striatum, and head direction cell circuitry. II. Neuroanatomical studies.

An animal's directional heading within its environment is encoded by the activity of head direction (HD) cells. In rodents, these neurons are found primarily within the limbic system in the interconnected structures that form the limbic HD circuit. In our accompanying report in this issue, we describe two HD cell populations located outside of this circuit in the medial precentral cortex (PrCM) and dorsal striatum (DS). These extralimbic areas receive their HD signals from the limbic system but do not provide critical input or feedback to limbic HD cells (Mehlman ML, Winter SS, Valerio S, Taube JS. J Neurophysiol 121: 350-370, 2019.). In this report, we complement our previous lesion and recording experiments with a series of neuroanatomical tracing studies in rats designed to examine patterns of connectivity between the PrCM, DS, limbic HD circuit, and related spatial processing circuitry. Retrograde tracing revealed that the DS receives direct input from numerous structures known to contain HD cells and/or other spatially tuned cell types. Importantly, these projections preferentially target and converge within the most medial portion of the DS, the same area in which we previously recorded HD cells. The PrCM receives direct input from a subset of these spatial processing structures. Anterograde tracing identified indirect pathways that could permit the PrCM and DS to convey self-motion information to the limbic HD circuit. These tracing studies reveal the anatomical basis for the functional relationships observed in our lesion and recording experiments. Collectively, these findings expand our understanding of how spatial processing circuitry functionally and anatomically extends beyond the limbic system into the PrCM and DS. NEW & NOTEWORTHY Head direction (HD) cells are located primarily within the limbic system, but small populations of extralimbic HD cells are found in the medial precentral cortex (PrCM) and dorsal striatum (DS). The neuroanatomical tracing experiments reported here explored the pathways capable of transmitting the HD signal to these extralimbic areas. We found that projections arising from numerous spatial processing structures converge within portions of the PrCM and DS that contain HD cells.