Thalamic Head Direction Cells Research Articles

Sensory and behavioral modulation of thalamic head-direction cells.

Head-direction (HD) neurons are thought to exclusively encode directional heading. In awake mice, we found that sensory stimuli evoked robust short-latency responses in thalamic HD cells, but not in non-HD neurons. The activity of HD cells, but not that of non-HD neurons, was tightly correlated to brain-state fluctuations and dynamically modulated during social interactions. These data point to a new role for the thalamic compass in relaying sensory and behavioral-state information.

Population dynamics of head-direction neurons during drift and reorientation

The head direction (HD) system functions as the brain’s internal compass1,2, classically formalized as a one-dimensional ring attractor network3,4. In contrast to a globally consistent magnetic compass, the HD system does not have a universal reference frame. Instead, it anchors to local cues, maintaining a stable offset when cues rotate5–8 and drifting in the absence of referents5,8–10. However, questions about the mechanisms that underlie anchoring and drift remain unresolved and are best addressed at the population level. For example, the extent to which the one-dimensional description of population activity holds under conditions of reorientation and drift is unclear. Here we performed population recordings of thalamic HD cells using calcium imaging during controlled rotations of a visual landmark. Across experiments, population activity varied along a second dimension, which we refer to as network gain, especially under circumstances of cue conflict and ambiguity. Activity along this dimension predicted realignment and drift dynamics, including the speed of network realignment. In the dark, network gain maintained a ‘memory trace’ of the previously displayed landmark. Further experiments demonstrated that the HD network returned to its baseline orientation after brief, but not longer, exposures to a rotated cue. This experience dependence suggests that memory of previous associations between HD neurons and allocentric cues is maintained and influences the internal HD representation. Building on these results, we show that continuous rotation of a visual landmark induced rotation of the HD representation that persisted in darkness, demonstrating experience-dependent recalibration of the HD system. Finally, we propose a computational model to formalize how the neural compass flexibly adapts to changing environmental cues to maintain a reliable representation of HD. These results challenge classical one-dimensional interpretations of the HD system and provide insights into the interactions between this system and the cues to which it anchors.

The Neural Correlates of Spatial Disorientation in Head Direction Cells.

While the brain has evolved robust mechanisms to counter spatial disorientation, their neural underpinnings remain unknown. To explore these underpinnings, we monitored the activity of anterodorsal thalamic head direction (HD) cells in rats while they underwent unidirectional or bidirectional rotation at different speeds and under different conditions (light vs dark, freely-moving vs head-fixed). Under conditions that promoted disorientation, HD cells did not become quiescent but continued to fire, although their firing was no longer direction specific. Peak firing rates, burst frequency, and directionality all decreased linearly with rotation speed, consistent with previous experiments where rats were inverted or climbed walls/ceilings in zero gravity. However, access to visual landmarks spared the stability of preferred firing directions (PFDs), indicating that visual landmarks provide a stabilizing signal to the HD system while vestibular input likely maintains direction-specific firing. In addition, we found evidence that the HD system underestimated angular velocity at the beginning of head-fixed rotations, consistent with the finding that humans often underestimate rotations. When head-fixed rotations in the dark were terminated HD cells fired in bursts that matched the frequency of rotation. This postrotational bursting shared several striking similarities with postrotational "nystagmus" in the vestibulo-ocular system, consistent with the interpretation that the HD system receives input from a vestibular velocity storage mechanism that works to reduce spatial disorientation following rotation. Thus, the brain overcomes spatial disorientation through multisensory integration of different motor-sensory inputs.

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.

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.

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.

Three-dimensional tuning of head direction cells in rats.

Head direction (HD) cells fire when the animal faces that cell's preferred firing direction (PFD) in the horizontal plane. The PFD response when the animal is oriented outside the earth-horizontal plane could result from cells representing direction in the plane of locomotion or as a three-dimensional (3D), global-referenced direction anchored to gravity. To investigate these possibilities, anterodorsal thalamic HD cells were recorded from restrained rats while they were passively positioned in various 3D orientations. Cell responses were unaffected by pitch or roll up to ~90° from the horizontal plane. Firing was disrupted once the animal was oriented >90° away from the horizontal plane and during inversion. When rolling the animal around the earth-vertical axis, cells were active when the animal's ventral surface faced the cell's PFD. However, with the rat rolled 90° in an ear-down orientation, pitching the rat and rotating it around the vertical axis did not produce directionally tuned responses. Complex movements involving combinations of yaw-roll, but usually not yaw-pitch, resulted in reduced directional tuning even at the final upright orientation when the rat had full visual view of its environment and was pointing in the cell's PFD. Directional firing was restored when the rat's head was moved back-and-forth. There was limited evidence indicating that cells contained conjunctive firing with pitch or roll positions. These findings suggest that the brain's representation of directional heading is derived primarily from horizontal canal information and that the HD signal is a 3D gravity-referenced signal anchored to a direction in the horizontal plane. NEW & NOTEWORTHY This study monitored head direction cell responses from rats in three dimensions using a series of manipulations that involved yaw, pitch, roll, or a combination of these rotations. Results showed that head direction responses are consistent with the use of two reference frames simultaneously: one defined by the surrounding environment using primarily visual landmarks and a second defined by the earth's gravity vector.

Impairment of the anterior thalamic head direction cell network following administration of the NMDA antagonist MK-801.

Head direction (HD) cells, found in the rodent Papez circuit, are thought to form the neural circuitry responsible for directional orientation. Because NMDA transmission has been implicated in spatial tasks requiring directional orientation, we sought to determine if the NMDA antagonist dizocilpine (MK-801) would disrupt the directional signal carried by the HD network. Anterior thalamic HD cells were isolated in female Long-Evans rats and initially monitored for baseline directional activity while the animals foraged in a familiar enclosure. The animals were then administered MK-801 at a dose of .05 mg/kg or 0.1 mg/kg, or isotonic saline, and cells were re-examined for changes in directional specificity and landmark control. While the cells showed no changes in directional specificity and landmark control following administration of saline or the lower dose of MK-801, the higher dose of MK-801 caused a dramatic attenuation of the directional signal, characterized by decreases in peak firing rates, signal to noise, and directional information content. While the greatly attenuated directional specificity of cells in the high dose condition usually remained stable relative to the landmarks within the recording enclosure, a few cells in this condition exhibited unstable preferred directions within and between recording sessions. Our results are discussed relative to the possibility that the findings explain the effects of MK-801 on the acquisition and performance of spatial tasks.

The irregular firing properties of thalamic head direction cells mediate turn-specific modulation of the directional tuning curve.

Head direction cells encode an animal's heading in the horizontal plane. However, it is not clear why the directionality of a cell's mean firing rate differs for clockwise, compared with counterclockwise, head turns (this difference is known as the “separation angle”) in anterior thalamus. Here we investigated in freely behaving rats whether intrinsic neuronal firing properties are linked to this phenomenon. We found a positive correlation between the separation angle and the spiking variability of thalamic head direction cells. To test whether this link is driven by hyperpolarization-inducing currents, we investigated the effect of thalamic reticular inhibition during high-voltage spindles on directional spiking. While the selective directional firing of thalamic neurons was preserved, we found no evidence for entrainment of thalamic head direction cells by high-voltage spindle oscillations. We then examined the role of depolarization-inducing currents in the formation of separation angle. Using a single-compartment Hodgkin-Huxley model, we show that modeled neurons fire with higher frequencies during the ascending phase of sinusoidal current injection (mimicking the head direction tuning curve) when simulated with higher high-threshold calcium channel conductance. These findings demonstrate that the turn-specific encoding of directional signal strongly depends on the ability of thalamic neurons to fire irregularly in response to sinusoidal excitatory activation. Another crucial factor for inducing phase lead to sinusoidal current injection was the presence of spike-frequency adaptation current in the modeled neurons. Our data support a model in which intrinsic biophysical properties of thalamic neurons mediate the physiological encoding of directional information.

Magnetic field polarity fails to influence the directional signal carried by the head direction cell network and the behavior of rats in a task requiring magnetic field orientation.

Many different species of animals including mole rats, pigeons, and sea turtles are thought to use the magnetic field of the earth for navigational guidance. While laboratory rats are commonly used for navigational research, and brain networks have been described in these animals that presumably mediate accurate spatial navigation, little has been done to determine the role of the geomagnetic field in these brain networks and in the navigational behavior of these animals. In Experiment 1, anterior thalamic head direction (HD) cells were recorded in female Long-Evans rats while they foraged in an environment subjected to an experimentally generated magnetic field of earth-strength intensity, the polarity of which could be shifted from one session to another. Despite previous work that has shown that the preferred direction of HD cells can be controlled by the position of familiar landmarks in a recording environment, the directional signal of HD cells was not influenced by the polarity of the magnetic field in the enclosure. Because this finding could be attributed to the animal being insensitive or inattentive to the magnetic field, in Experiment 2, rats were trained in a choice maze task dependent on the ability of the animals to sense the polarity of the experimentally controlled magnetic field. Over the course of 28 days of training, performance failed to improve to a level above chance, providing evidence that the spatial behavior of laboratory rats (and the associated HD network) is insensitive to the polarity of the geomagnetic field.

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.

A Continuous Attractor Network Model Without Recurrent Excitation: Maintenance and Integration in the Head Direction Cell System

Motivated by experimental observations of the head direction system, we study a three population network model that operates as a continuous attractor network. This network is able to store in a short-term memory an angular variable (the head direction) as a spatial profile of activity across neurons in the absence of selective external inputs, and to accurately update this variable on the basis of angular velocity inputs. The network is composed of one excitatory population and two inhibitory populations, with inter-connections between populations but no connections within the neurons of a same population. In particular, there are no excitatory-to-excitatory connections. Angular velocity signals are represented as inputs in one inhibitory population (clockwise turns) or the other (counterclockwise turns). The system is studied using a combination of analytical and numerical methods. Analysis of a simplified model composed of threshold-linear neurons gives the conditions on the connectivity for (i) the emergence of the spatially selective profile, (ii) reliable integration of angular velocity inputs, and (iii) the range of angular velocities that can be accurately integrated by the model. Numerical simulations allow us to study the proposed scenario in a large network of spiking neurons and compare their dynamics with that of head direction cells recorded in the rat limbic system. In particular, we show that the directional representation encoded by the attractor network can be rapidly updated by external cues, consistent with the very short update latencies observed experimentally by Zugaro et al. (2003) in thalamic head direction cells.

Peak firing rates of rat anterodorsal thalamic head direction cells are higher during faster passive rotations.

Head direction cells discharge selectively when the head of the animal is oriented in a specific direction. The goal of this study was to determine how sensory signals arising from passive rotations (e.g., triggered by vestibular stimulation and dynamic visual inputs) influence the responses of anterodorsal thalamic head direction cells in the absence of voluntary movement cues (e.g., motor command, efference copy, and associated kinesthetic signals). Three unrestrained rats consumed water from a reservoir at the center of a circular platform while passively subjected to sinusoidal rotatory oscillations at fast (153 +/- 27 degrees/s, sd) and slow (38 +/- 15 degrees/s) peak velocities. In 14 anterodorsal thalamic head direction cells, the preferred directions, angular response ranges and baseline firing rates remained stable, but the peak firing rates were, on average, 36% higher during the fast rotations (Wilcoxon matched-pairs test, p < 0.001; variation range: +11% to approximately +100%). No cell changed its peak firing rate by less than 10%, while three cells (21%) increased their peak firing rates by more than 50%. The velocity-dependent increase in peak firing rates was similar for left and right rotations, and the skewness of the directional response curves were not significantly different between left and right turns (Wilcoxon matched-pairs tests, n = 14, ns). These results show that sensory signals concerning self-movements modulate the responses of the head direction cells in the absence of active locomotion.

Active locomotion increases peak firing rates of anterodorsal thalamic head direction cells.

Head direction (HD) cells discharge selectively in macaques, rats, and mice when they orient their head in a specific ("preferred") direction. Preferred directions are influenced by visual cues as well as idiothetic self-motion cues derived from vestibular, proprioceptive, motor efferent copy, and command signals. To distinguish the relative importance of active locomotor signals, we compared HD cell response properties in 49 anterodorsal thalamic HD cells of six male Long-Evans rats during active displacements in a foraging task as well as during passive rotations. Since thalamic HD cells typically stop firing if the animals are tightly restrained, the rats were trained to remain immobile while drinking water distributed at intervals from a small reservoir at the center of a rotatable platform. The platform was rotated in a clockwise/counterclockwise oscillation to record directional responses in the stationary animals while the surrounding environmental cues remained stable. The peak rate of directional firing decreased by 27% on average during passive rotations (r(2) = 0.73, P < 0.001). Individual cells recorded in sequential sessions (n = 8) reliably showed comparable reductions in peak firing, but simultaneously recorded cells did not necessarily produce identical responses. All of the HD cells maintained the same preferred directions during passive rotations. These results are consistent with the hypothesis that the level of locomotor activity provides a state-dependent modulation of the response magnitude of AD HD cells. This could result from diffusely projecting neuromodulatory systems associated with motor state.

Modeling attractor deformation in the rodent head-direction system.

We present a model of the head-direction circuit in the rat that improves on earlier models in several respects. First, it provides an account of some of the unique characteristics of head-direction (HD) cell firing in the lateral mammillary nucleus and the anterior thalamus. Second, the model functions without making physiologically unrealistic assumptions. In particular, it implements attractor dynamics in postsubiculum and lateral mammillary nucleus without directionally tuned inhibitory neurons, which have never been observed in vivo, and it integrates angular velocity without the use of multiplicative synapses. The model allows us to examine the relationships among three HD areas and various properties of their representations. A surprising result is that certain combinations of purported HD cell properties are mutually incompatible, suggesting that the lateral mammillary nucleus may not be the primary source of head direction input to anterior thalamic HD cells.

A model of the rodent head direction system that accounts for unique properties of anterior thalamic head direction cells

We present a model of the rat head direction cell circuit that accounts for the recently discovered bimodality and distortion observed in the tuning curves of anterior thalamic head direction cells. This model also explains why anterior thalamic head direction cells show a constant amount of anticipation across all angular velocities.

Firing Properties of Head Direction Cells in the Rat Anterior Thalamic Nucleus: Dependence on Vestibular Input

Vestibular information influences spatial orientation and navigation in laboratory animals and humans. Neurons within the rat anterior thalamus encode the directional heading of the animal in absolute space. These neurons, referred to as head direction (HD) cells, fire selectively when the rat points its head in a specific direction in the horizontal plane with respect to the external laboratory reference frame. HD cells are thought to represent an essential component of a neural network that processes allocentric spatial information. The functional properties of HD cells may be dependent on vestibular input. Here, anterior thalamic HD cells were recorded before and after sodium arsanilate-induced vestibular system lesion. Vestibular lesions abolished the directional firing properties of HD cells. The time course of disruption in the directional firing properties paralleled the loss of vestibular function. Arsanilate-treated rats exhibited only minor changes in locomotor behavior, which were unlikely to account for the loss of direction-specific firing. Vestibular lesions also disrupted the influence of angular head velocity on anterior thalamic single-unit firing rates. Finally, a subset of anterior thalamic neurons recorded from vestibular-lesioned rats exhibited a pattern of intermittent firing bursts that were distinctly unrelated to HD. This novel anterior thalamic firing pattern has not been encountered in any vestibular-intact rat. These data suggest that: (1) the neural code for directional bearing is critically dependent on vestibular information; and (2) this loss of HD cell information may represent a neurobiological mechanism to account for the orientation and navigational deficits observed after vestibular dysfunction.

Visual and vestibular influences on head-direction cells in the anterior thalamus of the rat.

As a rat navigates through space, head-direction cells provide an ongoing signal of its momentary directional heading. This directional signal is thought to be generated, in part, by a dead-reckoning mechanism that uses angular motion information to constantly update the directional representation. This study investigated what kinds of angular motion information might be used for dead reckoning. Anterior thalamic head-direction cells were recorded from rats in a rotatable, cylindrical chamber, which could independently deliver visual motion cues and vestibular cues. Results suggest that both of these angular motion cues have an influence on head-direction cells and may thus be used for dead reckoning. The authors conclude that vestibular and visual movement cues work interactively, along with visual landmarks and motor signals, to determine the directional frame of reference.

Place cells, head direction cells, and the learning of landmark stability

Previous studies have shown that hippocampal place fields are controlled by the salient sensory cues in the environment, in that rotation of the cues causes an equal rotation of the place fields. We trained rats to forage for food pellets in a gray cylinder with a single salient directional cue, a white card covering 90 degrees of the cylinder wall. Half of the rats were disoriented before being placed in the cylinder, in order to disrupt their internal sense of direction. The other half were not disoriented before being placed in the cylinder; for these rats, there was presumably a consistent relationship between the cue card and their internal direction sense. We subsequently recorded hippocampal place cells and thalamic head direction cells from both groups of rats as they moved in the cylinder; between some sessions the cylinder and cue card were rotated to a new direction. All rats were disoriented before recording. Under these conditions, the cue card had much weaker control over the place fields and head direction cells in the rats that had been disoriented during training than in the rats that had not been disoriented. For the former group, the place fields often rotated relative to the cue card or completely changed their firing properties between sessions. In all recording sessions, the head direction cells and place cells were strongly coupled. It appears that the strength of cue control over place cells and head direction cells depends on the rat's learned perception of the stability of the cues.