F O C U S O N S PAT I A L C O G N I T I O N 
perspective
Our sense of direction: progress, controversies and
challenges
Kathleen E Cullen1 & Jeffrey S Taube2
In this Perspective, we evaluate current progress in
understanding how the brain encodes our sense of direction,
within the context of parallel work focused on how early
vestibular pathways encode self-motion. In particular, we
discuss how these systems work together and provide evidence
that they involve common mechanisms. We first consider the
classic view of the head direction cell and results of recent
experiments in rodents and primates indicating that inputs
to these neurons encode multimodal information during self-
motion, such as proprioceptive and motor efference copy
signals, including gaze-related information. We also consider
the paradox that, while the head-direction network is generally
assumed to generate a fixed representation of perceived
directional heading, this computation would need to be
dynamically updated when the relationship between voluntary
motor command and its sensory consequences changes.
Such situations include navigation in virtual reality and head-
restricted conditions, since the natural relationship between
visual and extravisual cues is altered.
Sense of direction versus a self-motion-detection system
Our ability to keep track of where we are going relative to where we
have been requires knowledge of our ongoing location and orienta-
tion. In everyday life, this ability, or sense of direction, depends on
the integration of both visual and nonvisual cues, including vestibular
and proprioceptive information. The visual system provides retinal
image-motion (optic flow) cues, which have long been known to
provide a powerful sense of motion through an otherwise stationary
environment1. In addition, extravisual cues make important contribu-
tions to navigation and are thought to contribute to path integration
or dead reckoning (Box 1) in the absence of visual cues (for review
see refs. 2,3). Notably, information sent to the brain by the vestibular
nerve allows the estimation of head displacement (both linear and
angular) in the absence of visual cues4–8. Further, during locomotion,
proprioceptive and/or motor-related signals also contribute signifi-
cantly to the estimation of self-motion. For example, estimates of dis-
tance traveled and self-velocity are more accurate when self-motion
is generated by active locomotion than when subjects are passively
1Department of Biomedical Engineering, The Johns Hopkins University, Baltimore,
Maryland, USA. 2Department of Psychological & Brain Sciences, Dartmouth College,
Hanover, New Hampshire, USA. Correspondence should be addressed to
K.E.C. (kathleen.cullen@jhu.edu) or J.S.T. (jeffrey.taube@dartmouth.edu).
Received 2 June; accepted 14 September; published online 26 October 2017;
doi:10.1038/nn.4658
nature neuroscience  VOLUME 20 | NUMBER 11 | NOVEMBER 2017 1465
moved9–12, and subjects can keep track of changes in heading during
active motion in the absence of vision5.
In everyday life, the vestibular system plays a vital role in a wide
range of functions from reflexes to the highest levels of voluntary
behavior. Notably, as we move through our environment, the ves-
tibular system explicitly detects and encodes our self-motion in six
dimensions: the semicircular canals and otolith end organs of the ves-
tibular system detect three dimensions of rotational head velocity and
three dimensions of translational head acceleration, respectively. This
self-motion information is in turn essential for generating the funda-
mental reflexes that guarantee stable gaze and posture during our eve-
ryday activities, namely the vestibulo-ocular, vestibulocervical, and
vestibulospinal reflexes13. Importantly, vestibular information is also
sent to higher centers via ascending pathways. In particular, two main
thalamocortical pathways—one anterior and the other posterior—
transmit vestibular information to the cortex (Fig. 1; reviewed in
refs. 14,15). Of the two, the anterior pathway has been more exten-
sively studied. It comprises direct projections from the anterior dorsal
thalamus to the retrosplenial cortex and multisynaptic projections
to the entorhinal cortex (via presubiculum and parasubiculum), and
it is thought to encode our static sense of direction during naviga-
tion and spatial memory tasks16. In contrast, the posterior pathway
originates in the vestibular nuclei and projects to the ventral posterior
thalamus, and then on to the somatosensory cortex and the parieto-
insular vestibular cortex17. This pathway has been less extensively
studied despite its likely contribution to the accurate coordination of
perception and detection of self-motion (reviewed in ref. 18).
This anatomical division then raises the question: are these two
ascending pathways independent or do they involve common mech-
anisms? Below, we first consider the prevailing view that during
navigation, vestibular information transmitted to the anterior tha-
lamocortical pathway is integrated to provide our sense of direction
by providing a critical input to the head-direction cell network. In
this context, neurons within the anterior thalamic nuclei are tuned
to specific static head directions. We then consider the implications
of recent work establishing that early vestibular pathways integrate
multimodal information to preferentially encode vestibular exaffer-
ence (i.e., motion that is not self-generated). The implications of these
recent studies are then considered in relation to both the ascending
sense of direction and self-motion detection pathways.
A quick review of the classic head direction system
Head direction (HD) cells, originally discovered in the rat dorsal pre-
subiculum (postsubiculum) by James Ranck in 1984 (see foreword19),
discharge in relation to the animal’s directional heading in the hori-
zontal plane, independent of the animal’s location and behavior20,21.
perspective

Box 1  Terms
Allothetic cues: external sensory cues that can be used as landmarks; these cues are used in an episodic (as opposed to continuous) manner.
Forward model: a process that predicts the expected sensory feedback of a motor command, allowing rapid error detection when actual and predicted feedback do
not match.
Idiothetic cues: internal body cues used to detect how the body and/or head is moving through space; to maintain spatial accuracy these cues must be used in a
continuous (as opposed to episodic) manner; for example, vestibular, proprioceptive, motor efference copy.
Optic flow: the flow of visual stimuli across the retina; this information can be used to determine how objects or the head is moving through the environment.
Path integration (dead reckoning): the process whereby an organism updates its spatial orientation through the use of self-motion cues as it moves
through the environment.
Spatial updating: the process whereby an organism updates its spatial orientation after movement or a period of time has elapsed.

In this regard their firing is analogous to a compass, which always systems, along with information about visual landmarks, work inter-
points in a particular direction (north) no matter where the compass actively and in synch with one another, but situations can arise in
is located, although for HD cells their activity does not appear to be which there is a conflict amongst these different types of sensory and
sensitive to the earth’s geomagnetic field22 but rather to landmark cues motor cues, an issue that we will return to below.
and the earth’s gravity axis21,23. Each HD cell is tuned to a different
direction, and a population of such cells uniformly represents the 360° The generation of a HD signal: vestibular pathways and ring
range. Their firing is thought to encode a continuous representation attractor networks
of the animal’s perceived directional heading. Peak firing rates vary The HD signal can be considered to be composed of two components:
across different cells and can range from a few spikes per s to more (i) the directional signal itself, which is theoretically based on the inte-
than 100 spikes per s. Figure 2a depicts three typical HD cells from gration of self-movement cues, and (ii) the anchoring of this signal
three different brains areas. Note the variations in peak firing rates, to a source, which subsequently defines the reference frame for the
as well as tuning widths, across the three cells, findings that are not signal. To understand how and where the HD signal is constructed,
well understood in terms of their functional roles. The variations researchers have recorded from one brain area following the lesioning
depicted are not necessarily characteristic of a particular brain area or inactivation of a second brain area. Using rats as the experimental
but in general can be observed across all areas where HD cells have
been identified. HD cells are found in many brain areas throughout
the limbic system, and studies have identified several brainstem sites Vestibular cortical Limbic/entorhinal
in rats that are responsible for generating the signal. Self-movement areas (PIVC)
Thalamus
cortex
cues are integrated in these brainstem areas, and the processed HD
signal is propagated rostrally through a network that includes the
anterodorsal thalamus (ADN), dorsal presubiculum, and entorhinal VPL ADN
cortex (reviewed in ref. 19). Visual landmark information is integrated
into this circuit via direct projections from visual cortex to the dorsal
presubiculum (and to a lesser extent, the retrosplenial cortex), which wa
y
th HDC
then exerts top-down control with projections to the lateral mammil- rp
a
network
io
lary nuclei (reviewed in ref. 24). HD cells have been mostly studied in er
st
Po
rats, and to a lesser extent in mice, but they have also been identified y
NPH/ wa
in monkeys25 and indirectly in humans26. SGN ath
rp
Early studies demonstrated the importance of the vestibular system r io
te Thalamocortical
An
for the HD signal, as bilateral neurotoxic lesions of the vestibular laby- VN pathways
rinth abolished the HD signal in the anterior thalamus27. Yet other
studies have shown how self-motion cues that are not vestibular in
origin can influence HD cell activity. For example, while HD cells
retain directional tuning during passive motion, in which only ves- Navigation
self-motion
tibular cues are present28, there can be differences in how HD cells perception
fire between active and passive locomotion29–31. Moreover, when HD
Debbie Maizels/Springer Nature

cells are monitored as rats move from a familiar environment to a

Gaze
novel one (in which they are unfamiliar with the visual landmark Afferents
VN stabilization
cues), the cells’ preferred firing directions remain stable between the (VOR)
Vestibular
two environments when animals are allowed to actively locomote to labyrinth
the novel environment32,33 but not when they are passively moved
Postural
(via a wheeled cart) to the novel environment33,34. Thus, despite the stabilization
presence of a normal vestibular signal when the animals are pas- (VSR)

sively transported, HD cells require information from other types of

movement signals (proprioception, motor efference copy) to main-
tain a stable orientation between a familiar and a novel environment.
Further, other studies that have manipulated optic flow cues (Box 1)
have shown that visual motion cues can influence HD cell activity35,36,
as well as make hippocampal place cells that are nondirectional in a
natural environment more directional37. Normally, these movement
Figure 1  Overview highlighting functions and projections of the
two ascending vestibular pathways: (i) the anterior vestibulothalamic
pathway through the nucleus prepositus and supragenual nucleus (NPH/SGN)
to the HD network (blue; see Fig. 2 for details) and (ii) the posterior
vestibulothalamic pathway through the ventral posterior lateral nucleus
(red). PIVC, parieto-insular vestibular cortex; VN, vestibular nuclei; VPL,
ventral posterior lateral thalamic nucleus.

1466 VOLUME 20 | NUMBER 11 | NOVEMBER 2017  nature neuroscience

 perspective

a 16 Presubiculum b Visual Other

cortex cortical areas
Firing rate (spike per s) 12

8 Entorhinal
Retrosplenial Dorsal cortex
4 cortex presubiculum
Granular Dysgranular

0
0 60 120 180 240 300 360 Hippocampus
Anterodorsal
Head direction (degrees) thalamic
nucleus
Anterodorsal thalamus
60

50 Lateral
Firing rate (spike/s)

mammillary
40 nucleus
30 HD signal
generation
20
Dorsal
10 tegmental Interpeduncular
nucleus nucleus
0
0 60 120 180 240 300 360 ?
Head direction (degrees)
Nucleus Supragenual
120 Lateral mammillary prepositus nucleus

Debbie Maizels/Springer Nature

100
Firing rate (spike/s)

Inhibitory
80 Excitatory
Medial PGRNd
60 HD cells
vestibular
AHV cells
nucleus
40 Place cells
20 Grid cells

0 Vestibular Proprioception
0 60 120 180 240 300 360
labyrinth Motor efference
Head direction (degrees)

Figure 2  Representative plots for HD cells and HD circuit. (a) Three typical HD cells are shown across three different brain areas. Peak firing rates in
each cell’s preferred firing direction can range from low (top) to medium (middle) to high (bottom) across different cells. Cells with low and high peak
firing rates can be observed in all brain areas. (b) Circuit diagram showing principal connections of areas containing HD, angular head velocity, place,
and grid cells. The bracket shows the site of the postulated ring attractor network that generates the HD signal. Red dashed line shows point in network
where lesions to brain areas below this level induce burst firing patterns in recorded ADN neurons; lesions above this level lead to the loss of the HD
signal in ADN without the presence of burstiness among the recorded neurons.

model, these studies have highlighted a circuit starting in the ves-
tibular nuclei and projecting through a series of brainstem nuclei,
including the nucleus prepositus, supragenual nucleus, and dorsal
tegmental nucleus, and then projecting to the lateral mammillary
nucleus and ADN thalamus19,38. A large percentage of the neurons
within the ADN can be classified as ‘classic’ HD cells, where the signal
is quite robust with a high signal-to-noise ratio. From the ADN, the
HD signal is projected rostrally to a number of areas, each of which
contains HD cells, including the presubiculum and parasubiculum,
retrosplenial, entorhinal and medial precentral cortices, and striatum
(Fig. 2b). There is good evidence that inputs from early vestibular
pathways are critical for the HD signal, as various types of vestibular
manipulations that interfere with a normal vestibular signal lead to
the loss of the HD signal. For example, lesions, inactivation, or occlu-
sions of the semicircular canals, as well as experiments in horizontal
canal-deficient mice, all lead to the loss of head-direction-specific
activity when recording from the ADN or postsubiculum (reviewed in
refs. 16,39). Given that the vestibular system conveys information
about how head orientation changes with head movements, the ves-
tibular system is an ideal candidate to provide information for updat-
ing the animal’s resultant head orientation following a head turn.
Specifically, the prevailing view is that information about the animals’
angular head velocity, which is encoded by neurons within the ves-
tibular nuclei, is conveyed from here to various cell types within the
brainstem nuclei, which all contain neurons whose firing also cor-
relates to angular head velocity40–42.
The most parsimonious computational models that have been pro-
posed to account for HD cell firing use continuous ring attractor
networks, which receive input from cells sensitive to angular head
velocity (reviewed in ref. 43). These networks contain interconnected
neurons, such that HD cells with similar preferred firing directions
have recurrent excitatory connections with one another, and HD cells
with opposing preferred firing directions inhibit one another. Once
activity is initiated, the network can sustain activity without outside
excitation. The local area of activity (referred to as the activity hill)
is moved around the ring to different directional headings following
inputs from self-motion-based (idiothetic; for example, angular head
velocity cells) or allothetic-based (landmark) sources (Box 1).
Based on studies that have investigated the anatomical substrate
of the HD signal, researchers have hypothesized that a ring attrac-
tor network may operate across the reciprocal connections between
the dorsal tegmental nuclei and the lateral mammillary nuclei
(Fig. 2b)39,44,45; cf. ref. 46. Consistent with this view are findings from
lesion and recording studies, which show that where in the HD cir-
cuit a lesion was placed determined the type of response observed in
downstream recording areas (Fig. 2b). Theoretically, a lesion placed
within the attractor network, or any area efferent to it, should lead
to disrupted firing in neurons further downstream to the lesion.

nature neuroscience  VOLUME 20 | NUMBER 11 | NOVEMBER 2017 1467

perspective
In contrast, a lesion placed afferent to the site of the attractor network
will leave the network’s internal connections intact, but the external
inputs will no longer be able to drive or reset the activity hill; under
these conditions, the network will be ‘untethered’ and the activity
hill will drift around the attractor ring. Precisely such responses were
found when lesions were made to brain areas associated with the
ascending vestibulothalamic pathway (i.e., nucleus prepositus, supra-
genual nucleus; Fig. 2b)16,39.
The vestibular system integrates multimodal information and
motor signals
Prior studies have demonstrated that multimodal information, including
proprioceptive, optic flow, and motor efference copy signals, can
influence HD cell activity, yet to date the question of how HD cells
actually integrate vestibular signals with other self-motion cues
remains open. Notably, as detailed above, the type of information
encoded by vestibular afferents is ideally suited to act as a spatial
updater for the HD network, and the prevailing view is that neu-
rons within the vestibular nuclei relay this information to the HD
cell network. However, the vestibular nuclei do much more than just
receive and encode a vestibular signal (i.e., inputs from the vestibular
sensory organs). Indeed, these nuclei integrate multimodal informa-
tion originating from a number of different sources including head,
body, and eye (gaze) motor commands, neck proprioceptive informa-
tion, and visual inputs in both rodents47,48 and primates (reviewed in
refs. 49,50). Thus, a remaining challenge is understanding how these
different sources of information contribute to the HD signal genera-
tion, as well as the implications of this integration for understanding
the nature of the HD signal itself.
Vestibular nuclei neurons can be grouped into two main catego-
ries on the basis of differences in their sensitivity to eye motion
and passive head motion, as well as connectivity. The first category,
vestibular-only (VO, alternatively termed non-eye-movement) neu-
rons, contribute to posture and self-motion perception. Specifically,
these neurons receive direct inputs from the vestibular nerve and
in turn drive vestibular spinal reflexes via their direct and indirect
projections to the spinal cord (reviewed in ref. 50). In addition, VO
neurons are a source of vestibular input to thalamocortical path-
ways51–53 and are reciprocally interconnected with the nodulus and
uvula of the vestibular cerebellum54. The second category of vestibu-
lar nuclei neurons are vestibulo-ocular reflex (VOR) neurons. These
neurons also receive direct inputs from the vestibular nerve and
project to extraocular motor neurons, thereby driving compensatory
VOR eye movements to ensure stabile gaze during self-motion. The
majority of VOR neurons are the position-vestibular-pause (PVP)
neurons, a distinct group of neurons deriving their name from the
signals they carry during passive head rotations and eye movements.
A second subclass of VOR pathway neurons, floccular target neu-
rons (FTN), receives input from the flocculus of the cerebellum as
well as from the vestibular nerve. FTNs similarly encode eye- as
well as head-related signals, and their responses complement those
of PVP neurons by ensuring the VOR remains calibrated during
daily activities.
During everyday activities, such as gaze behavior and locomotion,
the vestibular system is activated as a result of our own actively gener-
ated motor commands (Fig. 3a). Single-unit recording experiments
in monkeys have established that the afferent activity in the eighth
cranial nerve is the same for both actively self-generated movement
and externally applied movement, during both rotations and trans-
lations55–57. Further, these studies have shown that activity in the
eighth nerve is also independent of the animal’s current gaze behavior.
1468 VOLUME 20 | NUMBER 11 | NOVEMBER 2017  nature neuroscience
However, this comparable activity is not the case at the next stage of
vestibular processing in the vestibular nuclei. Instead, the responses of
both categories of vestibular nuclei neurons—VO neurons and VOR
neurons—are modulated in a behaviorally dependent manner.
Preferential encoding of passive versus active self-motion in the
vestibular nuclei
Experiments in head-unrestrained monkeys have established that
the sensory responses of VO neurons are suppressed during actively
generated movements (Fig. 3b)58–61. Specifically, while VO neurons
robustly respond to passive head movements their responses are
markedly (~70%) attenuated during active head movement. This is
the case for both rotational and translational motion, as well as across
different species of monkeys (reviewed in ref. 62) and in mice48. More
recent experiments controlling the association between intended and
actual head movement have established that a vestibular cancellation
signal is exclusively generated when the activation of neck proprio-
ceptors matches the motor-generated expectation63,64.
Because VO neurons mediate vestibulospinal reflex pathways, the
finding that their responses are suppressed during active motion has
important implications for voluntary motor control versus balance.
Specifically, while the vestibulospinal reflex is vital for stabilizing pos-
ture in response to unexpected movements, the stabilizing commands
produced by an intact vestibulospinal reflex would be counterproduc-
tive during voluntary movements. Accordingly, turning off vestibu-
lospinal reflexes is functionally advantageous. Further, because these
central vestibular neurons send ascending projections to the ventral
posterior thalamus, it follows that the self-motion signals relayed to
the higher-level cortical areas responsible for perception are attenu-
ated during active-motion vestibular information. Accordingly, these
findings are problematic for the classic view of how the HD signal is
generated, resulting in the following conundrum: if the main ascend-
ing vestibular pathway from the vestibular nuclei does not robustly
encode self-motion during active movements because the signal is
dramatically suppressed, how is the HD signal computed?65,66
Finally, the finding that the vestibular pathway does not encode
self-motion during active movements raises the question of whether
HD cell responses differ between active versus passive head move-
ments. Some studies have shown that the HD signal is attenuated
during passive head turns, particularly when the animal is tightly
restrained in a towel29–31, but other studies using head-fixed animals
have shown that HD cells fire similarly for both active and passive
motion—at least for cells in the ADN thalamus28. Thus, we return to
the initial quandary: if vestibular activity at the level of the vestibular
nuclei is largely suppressed during active head movements, how does
the vestibular system drive HD cell discharge?
Conundrum: building HD signal during active head movements
One possible answer to the conundrum raised above is that other
self-motion cues carried by VO neurons during active movements are
integrated by the HD network to compute an estimate of direction.
While this is not the case in rhesus monkeys60,61, recordings from
the vestibular nuclei in mice have shown that, in contrast to monkey
neurons, VO neurons in rodents encode a static neck-position signal
in both active and passive conditions48. Notably, this propriocep-
tive-derived and/or neck motor signal appears to remain robust (i.e.,
unchanged) for active as well as passive movements. Nevertheless, it
remains the case that, in both mice and monkeys, the signals coded
by VO neurons significantly differ between active and passive condi-
tions, with neurons displaying less modulation during active move-
ments compared to during passive ones. This finding then raises the
 perspective

related possibility that the VO neuron signal is decoded by the HD a Cerebellum

network in a context-dependent manner. Specifically, while the head- Internal

motion-related modulation of VO neurons is markedly suppressed model
Estimate of
during active head motion in both species, it is not completely can- sensory feedback
Actual sensory feedback
celled. Thus, theoretically, this attenuated input could be up-weighted during self-motion Match
in the active condition and/or combined with other available inputs
Cancellation
at the level of the HD network (for example, proprioceptive-derived signal
signals and/or motor efference). This possibility raises the questions Vestibular input
Selective
coding of
of whether it is the case and if so, what circuits underlie the required • passively–applied
Vestibular
sensors
Vestibular
nuclei
passive
• actively–generated vestibular
up-weighting and/or integration? stimulation

Eye-movement information and the HD network? b Normal conditions c Learning

As reviewed above, the vestibular nuclei contain a second category (match) (initial mismatch)
Passive Active Early Middle Late
of neurons in addition to VO neurons, namely VOR (i.e., PVP and (1–5) (26–30) (46–50)
FTN) neurons. These neurons encode eye- as well as head-motion

100° per s 50 spikes per s

Head
information and project to oculomotor centers to control VOR eye velocity
movements. Unlike VO neurons, VOR neurons do not preferentially
encode passive head motion, thus raising the question of whether 100 ms

inputs from these neurons might be combined by the HD network to Firing

compute an estimate of HD. However, these neurons integrate eye- rate

movement commands with vestibular information such that they

encode head motion in a manner that depends fundamentally on Time
the animal’s current gaze strategy. Specifically, the responses of PVP
neurons are suppressed whenever animals redirect their gaze (i.e.,
during saccades and smooth pursuit) by an inhibitory gaze-command
Internal
signal. Similarly, FTN neurons carry gaze-related as well as vestibular Initial model
information. Thus, while these neurons could theoretically provide mismatch updated

head-movement-related inputs to the HD network, they would also

transmit gaze-related inputs. d
Indeed, VOR neurons project to the nucleus prepositus, a structure
implicated in the circuit connecting the vestibular nuclei to HD net-

Debbie Maizels/Springer Nature

work (Fig. 2). The nucleus prepositus is also known as the oculomotor
integrator, due to its central role in shaping eye movements (for review,
see ref. 67). Accordingly, understanding the role played by the nucleus
prepositus, an area in which lesions have been shown to disrupt the HD
signal68, is complicated by the fact that this structure also contributes to
controlling gaze. Moreover, this observation raises the possibility that
the ascending HD signal from the vestibular nuclei to the ADN thala-
mus does not exclusively transmit angular head-direction information
derived from the vestibular labyrinth but also encodes eye-position
information. In sum, none of the three classes of output neurons in the
monkey vestibular nuclei (VO, PVP, and FTNs), neurons that would be
the potential relays to the HD network, actually encode purely vestibular
information during voluntary behavior (active head movements); rather
they are either attenuated during voluntary self-motion or encode some
type of eye-position signal along with any head-movement signal.
In monkeys, the vast majority of nucleus prepositus neurons
respond only to eye movements, with a subset (~20%) responding to
both eye movements and vestibular stimulation69–71. Thus, the pri-
mate nucleus prepositus predominately outputs eye-in-head position
and velocity information, even during voluntary head motion (for
example, see ref. 69). Given that the nucleus prepositus targets regions
projecting multisynaptically to the presubiculum 19, a key question
arises: to what extent is the HD cell an indicator of the animal’s head
direction, as opposed to the direction of its gaze? Unfortunately, to
date, no studies in rodents have recorded HD cells while simultane-
ously tracking eye position, so it is currently unknown whether rodent
HD cells respond to changes in gaze direction. We must therefore
turn our attention to primate studies that have recorded from hip-
pocampal and parahippocampal areas while monitoring eye position
and gaze direction.
Figure 3  Learning new relationships between motor commands and
sensory feedback during self-motion.(a,b) A cancellation signal is sent
to the vestibular nuclei when sensory feedback matches the expected
sensory consequence of motor command (a), resulting in the suppression
of responses to self-generated vestibular stimulation at the first central
stage of processing in the vestibular nuclei (b; compare blue and green
traces). (c) When the normal relationship between the motor command
and resultant movement is altered for active head movements, there is
an initial mismatch (red arrow) between expected and actual sensory
feedback. As a result, these vestibular neurons robustly respond to self-
generated vestibular stimulation (dashed red trace shows predicted
response based on sensitivity to passive vestibular stimulation). Then, after
a learning phase (gray box), the brain updates its model of the expected
sensory consequence of the motor command (green arrow). (d) In head-
fixed or head-restrained VR-based protocols there is effectively a mismatch
between multisensory feedback (both vestibular and proprioceptive) and
optic flow. Dynamic updating of the brain’s model of the expected sensory
consequence of the motor command requires tracking the comparison of
the predictive and actual sensory feedback signals.
In a series of studies in monkeys, Rolls and colleagues mostly iden-
tified spatial-view cells that responded when a certain part of the
environment was in the animal’s field of view, as opposed to location

nature neuroscience  VOLUME 20 | NUMBER 11 | NOVEMBER 2017 1469

perspective
or HD72,73. The majority of these cells were localized to the hippocam-
pus rather than areas now known to contain HD cells. More recently,
recordings from the entorhinal cortex in head-fixed monkeys viewing
images on a video monitor showed that many cells fired based on the
direction of the monkey’s saccadic eye movements74. It is notable,
however, that this signal appears to be based on an egocentric refer-
ence frame, rather than the allocentric one seen for rodent HD cells.
Nonetheless, together the above studies demonstrate the importance
of eye position- and eye movement-related information as important
determinants for cell firing—at least for monkeys. In contrast, other
studies have recorded cells in monkeys that resemble HD cells that
use an allocentric framework. Robertson et al.25 originally identified
five such cells in parahippocampal areas (four in presubiculum and
one in entorhinal cortex), and more recently, others have identified
HD cells in the anterior thalamus75. It is noteworthy, however, that
the proportion of HD cells in these studies was small (~5%) in com-
parison to rodent studies, which found 50% and 25% of cells in the
ADN and postsubiculum, respectively20,30. Furthermore, while the
HD signals recorded in these primate studies were independent of
eye position, whether rodent HD cells encode true HD and not gaze-
direction responses remains an open question.
Rapid updating of a forward model underlies the suppression of
vestibular signals during active movement
The suppression of vestibular input resulting from active motion is
common across species including mice48, squirrel monkeys76, and
macaque monkeys (rhesus60 and fasicularis77). As mentioned above,
recent studies in rhesus monkeys that focused on understanding the
mechanism underlying this cancellation suggest that the brain gener-
ates a sensory expectation based on its motor output, which is then
compared with the actual sensory input (reviewed in refs. 49,50).
Specifically, vestibular responses are suppressed at the level of the
vestibular nucleus when there is a match between the expected conse-
quences of self-generated movement and resultant sensory feedback63
(Fig. 3a). Moreover, this mechanism appears to be cerebellar-depend-
ent, and it allows selective encoding of passive self-motion at the
earliest central stage of vestibular processing78,79.
A recent experiment emphasized the importance of prior experi-
ence in determining what constitutes a match between the expected
sensory consequences of self-generated movement and the actual
sensory feedback during motion 78. As monkeys made voluntary
head movements, the relationship between the motor command
produced to generate the movement and the actual resultant move-
ment was altered to produce a mismatch. Specifically, constant
resistive torque was applied that initially reduced the monkey’s
head motion by half. In this condition, vestibular nuclei neurons
first responded as if head movement was externally generated,
but the cancellation of active vestibular input re-emerged over the
same time course as the ongoing behavioral learning (~40–50 head
movements; Fig. 3c). Indeed, this result provides clear evidence for
the rapid updating of a forward model (Box 1) that enables the ves-
tibular system to learn to expect unexpected head motion inputs.
Accordingly, what constitutes a match between (i) the expected
sensory consequences of self-generated movement and (ii) the
actual sensory feedback is continually updated as a function of
recent experience.
In this context, it is noteworthy that the HD network is generally
assumed to generate a stable representation of the animal’s current or
anticipated head direction. Yet the expected correspondence between
the sensory and motor cues that are inputs into this network require
updating whenever there is a change in the relationship between the
1470 VOLUME 20 | NUMBER 11 | NOVEMBER 2017  nature neuroscience
expected and actual sensory feedback. This constraint is particularly
relevant to studies of navigation based on experimental designs in
which this relationship is mismatched relative to what occurs in eve-
ryday life. For example, in virtual reality (VR) the lack of normal
multisensory feedback (both vestibular and proprioceptive) during
VR effectively results in a mismatch condition between the system’s
internal state and resultant optic flow (Fig. 3d). Specifically, the infor-
mation about the subject’s movement based on visual information
would conflict with vestibular and proprioceptive cues. Furthermore,
there would also be a mismatch between the expected and actual
sensory vestibular and proprioceptive feedback experienced in studies
using head-fixed or head-restrained protocols. Thus, in this context,
knowing one’s perceived directional heading in the real world versus
in an immersive world (i.e., in a video game), requires that the brain
learns to switch back and forth between states in which the relation-
ships between these cues are different. Further experiments will be
required to understand the circuits and mechanisms that underlie
this ability.
Implications for navigation in immersive environments
The considerations discussed above raise the fundamental question of
how HD cells respond in mismatched VR and head-restrained condi-
tions versus during actual navigation in the real world. Specifically,
are the pathways that encode our sense of direction updated in such
conditions to reflect a modified forward model that no longer expects
the same sensory feedback from extravisual sources (i.e., vestibular
and proprioceptive), as would be experienced under natural condi-
tions? And if so, what is the time course of this updating and what
are its implications for understanding how the brain encodes our
sense of direction? Can this updating be observed in HD cells? If so,
in contrast with common wisdom, this outcome could imply that the
network generating the HD cell does not generate a constant signal
representing the subject’s perceived directional heading in the real
world but rather a perception of their directional heading in the real-
ity they are immersed in, whether it is a VR environment or during
sleep and dreaming.
How spatial cells behave under VR conditions is an important issue
because most spatial studies in humans employ functional imaging
techniques on subjects who are performing a spatial task while lying
supine with their head fixed and viewing a video monitor—meaning
that there is no active vestibular signal, motor-efference feedback, or
proprioceptive feedback. These issues have been reviewed in more
detail80,81, but the bottom line is that navigation in the virtual world
is quite different than navigation in the real world, particularly in
terms of the sensory and motor systems that are activated, which has
important implications for interpreting underlying mechanisms.
What we do know, based on numerous behavioral studies, is that
accurately performing a spatial task using a video monitor versus
navigating successfully are two different things. For instance, rodents
can accurately perform a spatial task, even when their HD cell system
is not functional82, suggesting that different spatial tasks employ dif-
ferent computations that most likely require multiple brain areas and
neural systems. Establishing how and where these systems interact
and are integrated is critical for understanding the neural mechanisms
underlying accurate navigation in both the real world and in VR con-
ditions. The extent to which accurate performance can be maintained
in either desktop or VR spatial tasks in the face of disruption to the
HD system, and by default the grid cell system, which is dependent
on the HD system83, is not known.
In this context, it is interesting to consider how HD cells might
fire when a subject is immersed in a video game in which they adopt

the spatial perspective of the avatar but still maintain an awareness
of their orientation with the surrounding environment. Under these
circumstances, would HD signals adopt the reference frame related
to the video game or to the surrounding real world? Would HD cells
across all brain areas adopt the same reference frame simultaneously
and dynamically switch between representations, or would the HD
cell population split into different representations? Recent recordings
from the rat retrosplenial cortex have found different types of HD
cells, some of which are tied to the global environment and some of
which are tied to the local environment84. Remarkably, a third cell
type, located only in the dysgranular retrosplenial cortex, encoded
both local and global reference frames concurrently, thus having two
preferred firing directions in the same environment and potentially
providing a basis for how we simultaneously maintain multiple spatial
representations for different environments.
Similarly to immersion in a video game, one might consider how
HD cells respond when imagining a situation that involves navigation:
for example, when sitting at home and thinking about how you might
navigate between two places that are distant from your home. Again,
would HD signals adopt the reference frame related to the imagined
locations or to the surrounding real world? Acquiring answers to
this question will be important to fully understand the brain mecha-
nisms underlying spatial orientation and navigation. A few studies
have begun to address this issue. For instance, Peyrache et al.46 moni-
tored multiple HD cells simultaneously during sleep and found that
their firing retained the temporal correlation structure between each
other. Further, network activity that occurred during the awake state
was replayed during sleep at a 10× higher rate, suggesting that HD
cell activity is not always tied to real world events. Whether HD cell
activity across other brain areas will contain these same properties is
an interesting question, as one could imagine that certain brain areas
may only be associated with real-world events, while other brain areas
are more involved in imaginative states.
It is important to consider these findings in light of what’s known
about hippocampal place cell activity in VR, where results have been
less consistent. Some labs have reported robust place cell firing in VR
compared to the real-world85, while others have reported either an
absence of such firing or a lower percentage of cells showing loca-
tion-specific firing86,87. This discrepancy is not due to species differ-
ences, because all the studies used rats. Currently, the most plausible
reason(s) is that substantial vestibular, proprioceptive, and motor
information is needed in order to observe robust place-like activity.
In the studies involving less location-specific activity, the rats were
either head- or body-fixed, which limited the amount of vestibular
and proprioceptive stimuli. In contrast, in the study that observed
robust place cell firing85, which also reported the presence of HD cells
and grid cells, the rats were in a harness, and though they were con-
fined in place (because their limb movements were directed to move
a track ball), they were relatively free to rotate their head and body.
Thus, although there was an absence in activating the linear compo-
nent of the vestibular system (otoliths), the angular component of the
vestibular system (canals) and proprioceptors in the neck and body
would have been activated normally. In sum, if both vestibular and
proprioceptive stimuli are needed in order to activate normal spatial
firing, then monitoring subjects in VR conditions where these stimuli
are limited may not reflect an accurate representation of the underly-
ing neural processes that occur during real world navigation.
HD cells in three dimensions and the vestibular system
Over the past decade, several studies in rodents have examined
how HD cells respond outside the horizontal plane (reviewed in
nature neuroscience  VOLUME 20 | NUMBER 11 | NOVEMBER 2017 1471
perspective
refs. 88,89). HD cells in bats, a species that routinely moves in a three-
dimensional world, display three-dimensional tuning and maintain
directional tuning when inverted90. In contrast, while rat HD cells
display directional tuning in the vertical plane, their tuning is lost
when the rat is inverted82,91. One hypothesis proposed to explain
these results is that HD cells define their reference frame based on
the animal’s plane of locomotion such that the vertical plane is rep-
resented as an extension of the floor89. An alternative hypothesis,
referred to as the mosaic hypothesis, is that the animal uses two rules
for updating their directional heading: (i) a rule for yaw rotations
around the dorsal–ventral axis and (ii) a rule for rotations of the ani-
mal’s dorsal–ventral axis around the gravity-defined vertical axis92.
Notably, neither of these proposals can account for the absence of
directional firing when the animal is inverted.
Recently, Shinder and Taube23 recorded HD cells from head-fixed
rats as they were passively positioned in different orientations in all
three rotational planes. Responses in large part could be explained
in relation to the animal’s position relative to the earth’s gravitational
axis. Using a reference frame that is at least partially defined by gravity
would account for the finding that disruption of the otolith organs,
which are sensitive to gravity, impairs HD cell activity93. Indeed,
linking the reference frame to gravity is consistent with recent
findings in monkeys that reported neurons in the anterior thalamus
tuned to pitch-and-roll orientation relative to gravity94. Finally,
vestibular nuclei neurons show strong attenuation to otolith-related
input during voluntary changes in head position 95. Thus, taken
together, while the vestibular system, at the level of both the semi-
circular canals and the otolith organs, appears deeply involved in the
HD signal, future experiments will be required to understand how
vestibular and extravestibular sensory signals, as well as motor inputs,
are integrated to build an estimation of three-dimensional orientation
during active navigation.
Outlook and conclusions
In sum, to date there has been much progress in understanding the
neural mechanisms underlying our sense of direction, as well as how
early vestibular pathways encode self-motion. Disruption of the
peripheral vestibular system impairs the directional firing patterns
of HD cells27, as well as theta rhythm in the hippocampus (reviewed
in ref. 96) and medial entorhinal cortex97. Further the grid-cell signal
in the medial entorhinal cortex is dependent on both an intact HD
signal83 and a theta signal98,99 and is believed to be intimately involved
in navigational processes. Taken together, it follows that the vestibular
system is also critically involved in the generation of the grid-cell sig-
nal, although this point has not yet been tested directly. Interestingly,
the distinction between the effects of active versus passive motion
on vestibular neurons is recapitulated for grid cells, in the sense that
active movement is required for a normal grid cell signal100.
Neurons at the first central stage of vestibular processing encode
proprioceptive, gaze, and head motor-efference copy, as well as ves-
tibular signals—all cues that affect both HD and grid cell firing.
Moreover, this multimodal information is transmitted in a behavio-
rally dependent manner that is rapidly updated when the relationship
between voluntary motion and the actual sensory input to the brain
changes. Thus, while the ascending vestibular pathway through the
anterior thalamus is likely important for navigation, as it conveys the
HD signal rostrally, there are open questions regarding how this path-
way utilizes vestibular signals versus other sensory cues and motor
signals during navigation. In contrast, the ascending vestibular path-
way through the ventral posterior thalamus is likely more involved
with one’s perceived sense of self-motion (whether such motion is
perspective
relative to a visual scene on a video monitor or relative to the exter-
nal world). Where and how these two ascending vestibular pathways
are merged and integrated in the cortex remains an open question,
and further appreciation of this integration will ultimately be key to
understanding the neural mechanisms underlying our sense of direc-
tion and accurate navigation in both the three-dimensional real world
and in VR conditions.
COMPETING FINANCIAL INTERESTS
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reprints/index.html. Publisher’s note: Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional affiliations.
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