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).

Region-Specific Summation Patterns Inform the Role of Cortical Areas in Selecting Motor Plans.

Given an instruction regarding which effector to move and what location to move to, simply adding the effector and spatial signals together will not lead to movement selection. For this, a nonlinearity is required. Thresholds, for example, can be used to select a particular response and reject others. Here we consider another useful nonlinearity, a supralinear multiplicative interaction. To help select a motor plan, spatial and effector signals could multiply and thereby amplify each other. Such an amplification could constitute one step within a distributed network involved in response selection, effectively boosting one response while suppressing others. We therefore asked whether effector and spatial signals sum supralinearly for planning eye versus arm movements from the parietal reach region (PRR), the lateral intraparietal area (LIP), the frontal eye field (FEF), and a portion of area 5 (A5) lying just anterior to PRR. Unlike LIP neurons, PRR, FEF, and, to a lesser extent, A5 neurons show a supralinear interaction. Our results suggest that selecting visually guided eye versus arm movements is likely to be mediated by PRR and FEF but not LIP.

NMDA blockade inhibits experience-dependent modification of anterior thalamic head direction cells.

Head Direction (HD) cells of the rodent Papez circuit are thought to reflect the spatial orientation of the animal. Because NMDA transmission is important for spatial behavior, we sought to determine the effects of NMDA blockade on the basic directional signal carried by HD cells and on experience-dependent modification of this system. In Experiment 1, HD cells were recorded from the anterior dorsal thalamus in female Long-Evans rats while they foraged in a familiar enclosure following administration of the NMDA antagonist CPP or saline. While the drug produced a significant decrease in peak firing rates, it failed to affect the overall directional specificity and landmark control of HD cells. Experiment 2 took place over 2 days and assessed whether the NMDA antagonist would interfere with the stabilization of the HD network in a novel environment. On Day 1 the animal was administered CPP or saline and placed in a novel enclosure to allow the stabilization of the HD signal relative to the new environmental landmarks. On Day 2 the animal was returned to the formerly novel enclosure to determine if the enclosure specific direction-dependent activity established on Day 1 was maintained. In contrast to HD cells from control animals, cells from animals receiving CPP during the initial exposure to the novel enclosure did not maintain the same direction-dependent activity relative to the enclosure in the subsequent drug-free exposure. These findings demonstrate that plasticity in the HD system is dependent on NMDA transmission similar to many other forms of spatial learning.

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.

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.

Where am I and how will I get there from here? A role for posterior parietal cortex in the integration of spatial information and route planning.

The ability of an organism to accurately navigate from one place to another requires integration of multiple spatial constructs, including the determination of one's position and direction in space relative to allocentric landmarks, movement velocity, and the perceived location of the goal of the movement. In this review, we propose that while limbic areas are important for the sense of spatial orientation, the posterior parietal cortex is responsible for relating this sense with the location of a navigational goal and in formulating a plan to attain it. Hence, the posterior parietal cortex is important for the computation of the correct trajectory or route to be followed while navigating. Prefrontal and motor areas are subsequently responsible for executing the planned movement. Using this theory, we are able to bridge the gap between the rodent and primate literatures by suggesting that the allocentric role of the rodent PPC is largely analogous to the egocentric role typically emphasized in primates, that is, the integration of spatial orientation with potential goals in the planning of goal-directed movements.

Combined blockade of serotonergic and muscarinic transmission disrupts the anterior thalamic head direction signal.

Head direction (HD) cells have been speculated to be part of a network mediating navigational behavior. Previous work has shown that combined administration of serotonergic and muscarinic antagonists eliminates hippocampal theta activity and produces navigational deficits more severe than blockade of either neurotransmitter system alone. The authors sought to assess this effect on the directional characteristics of HD cells. HD cells were recorded from the anterior dorsal thalamus of Long-Evans rats before and after administration of the serotonergic antagonist methiothepin, the muscarinic antagonist scopolamine, both drugs, or saline. Combined drug administration produced HD cells with preferred directions that drifted within recording sessions. In addition, cells showed shifts in the preferred directions at the start of a session relative to the position of the major landmarks, suggesting that combined drug administration led to deficits in landmark control of the HD system. Single drug exposures to methiothepin or scopolamine did not noticeably affect the directional characteristics of HD cells. This finding that navigation-impairing drugs can disrupt the HD signal provides further evidence that this network plays an important role in navigational behavior.

Landmark control and updating of self-movement cues are largely maintained in head direction cells after lesions of the posterior parietal cortex.

Head direction (HD) cells discharge as a function of the rat's directional orientation with respect to its environment. Because animals with posterior parietal cortex (PPC) lesions exhibit spatial and navigational deficits, and the PPC is indirectly connected to areas containing HD cells, we determined the effects of bilateral PPC lesions on HD cells recorded in the anterodorsal thalamus. HD cells from lesioned animals had similar firing properties compared to controls and their preferred firing directions shifted a corresponding amount following rotation of the major visual landmark. Because animals were not exposed to the visual landmark until after surgical recovery, these results provide evidence that the PPC is not necessary for visual landmark control or the establishment of landmark stability. Further, cells from lesioned animals maintained a stable preferred firing direction when they foraged in the dark and were only slightly less stable than controls when they self-locomoted into a novel enclosure. These findings suggest that PPC does not play a major role in the use of landmark and self-movement cues in updating the HD cell signal, or in its generation.

Preparatory delay activity in the monkey parietal reach region predicts reach reaction times.

To acquire something that we see, visual spatial information must ultimately result in the activation of the appropriate set of muscles. This sensory to motor transformation requires an interaction between information coding target location and information coding which effector will be moved. Activity in the monkey parietal reach region (PRR) reflects both spatial information and the effector (arm or eye) that will be used in an upcoming reach or saccade task. To further elucidate the functional role of PRR in visually guided movement tasks and to obtain evidence that PRR signals are used to drive arm movements, we tested the hypothesis that increased neuronal activity during a preparatory delay period would lead to faster reach reaction times but would not be correlated with saccade reaction times. This proved to be the case only when the type of movement and not the spatial goal of that movement was known in advance. The correlation was strongest in cells that showed significantly more activity on arm reach compared with saccade trials. No significant correlations were found during delay periods in which spatial information was provided in advance. These data support the idea that PRR constitutes a bottleneck in the processing of spatial information for an upcoming arm reach. The lack of a correlation with saccadic reaction time also supports the idea that PRR processing is effector specific, that is, it is involved in specifying targets for arm movements but not targets for eye movements.

Degradation of head direction cell activity during inverted locomotion.

Head direction (HD) cells in the rat limbic system carry information about the direction the head is pointing in the horizontal plane. Most previous studies of HD functioning have used animals locomoting in an upright position or ascending/descending a vertical wall. In the present study, we recorded HD cell activity from the anterodorsal thalamic nucleus while the animal was locomoting in an upside-down orientation. Rats performed a shuttle-box task requiring them to climb a vertical wall and locomote across the ceiling of the apparatus while inverted to reach an adjoining wall before ascending into the reward compartment. The apparatus was oriented toward the preferred direction of the recorded cell, or the 180 degrees opposite direction. When the animal was traversing the vertical walls of the apparatus, the HD cells remained directionally tuned as if the walls were an extension of the floor. When the animal was locomoting inverted on the ceiling, however, cells showed a dramatic change in activity. Nearly one-half (47%) of the recorded cells exhibited no directional specificity during inverted locomotion, despite showing robust directional tuning on the walls before and after inversion. The remaining cells showed significantly degraded measures of directional tuning and random shifts of the preferred direction relative to the floor condition while the animal was inverted. It has previously been suggested that the HD system uses head angular velocity signals from the vestibular system to maintain a consistent representation of allocentric direction. These findings suggest that being in an inverted position causes a distortion of the vestibular signal controlling the HD system.

Rat head direction cell responses in zero-gravity parabolic flight.

Astronauts working in zero-gravity (0-G) often experience visual reorientation illusions (VRIs). For example, when floating upside down, they commonly misperceive the spacecraft floor as a ceiling and have a reversed sense of direction. Previous studies have identified a population of neurons in the rat's brain that discharge as a function of the rat's head direction (HD) in a gravitationally horizontal plane and is dependent on an intact vestibular system. Our goal was to characterize HD cell discharge under conditions of acute weightlessness. Seven HD cells in the anterior dorsal thalamus were monitored from rats aboard an aircraft in 0-G parabolic flight. Unrestrained rats locomoted in a clear plexiglas rectangular chamber that had wire mesh covering the floor, ceiling, and one wall. The chamber and surrounding visual environment were relatively up-down symmetrical. Each HD cell was recorded across forty 20-s episodes of 0-G. All HD cells maintained a significant direction-specific discharge when the rat was on the chamber floor during the 0-G and also during the hypergravity pull-out periods. Three of five cells also showed direction-specific responses on the wall in 1-G. In contrast, direction-specific discharge was usually not maintained when the rat locomoted on the vertical wall or ceiling in 0-G. The loss of direction-specific firing was accompanied by an overall increase in background firing. However, while the rat was on the ceiling, some cells showed occasional bursts of firing when the rat's head was oriented in directions that were flipped relative to the long axis of symmetry of the chamber compared with the cell's preferred firing direction on the floor. This finding is consistent with what might be expected if the rat had experienced a VRI. These responses indicate that rats maintain a normal allocentric frame of reference in 0-G and 1-G when on the floor, but may lose their sense of directional heading when placed on a wall or ceiling during acute exposures to 0-G.

Hippocampal place cell instability after lesions of the head direction cell network.

The occurrence of cells that encode spatial location (place cells) or head direction (HD cells) in the rat limbic system suggests that these cell types are important for spatial navigation. We sought to determine whether place fields of hippocampal CA1 place cells would be altered in animals receiving lesions of brain areas containing HD cells. Rats received bilateral lesions of anterodorsal thalamic nuclei (ADN), postsubiculum (PoS), or sham lesions, before place cell recording. Although place cells from lesioned animals did not differ from controls on many place-field characteristics, such as place-field size and infield firing rate, the signal was significantly degraded with respect to measures of outfield firing rate, spatial coherence, and information content. Surprisingly, place cells from lesioned animals were more likely modulated by the directional heading of the animal. Rotation of the landmark cue showed that place fields from PoS-lesioned animals were not controlled by the cue and shifted unpredictably between sessions. Although fields from ADN-lesioned animals tended to have less landmark control than fields from control animals, this impairment was mild compared with cells recorded from PoS-lesioned animals. Removal of the prominent visual cue also led to instability of place-field representations in PoS-lesioned, but not ADN-lesioned, animals. Together, these findings suggest that an intact HD system is not necessary for the maintenance of place fields, but lesions of brain areas that convey the HD signal can degrade this signal, and lesions of the PoS might lead to perceptual or mnemonic deficits, leading to place-field instability between sessions.

Non-spatial, motor-specific activation in posterior parietal cortex.

A localized cluster of neurons in macaque posterior parietal cortex, termed the parietal reach region (PRR), is activated when a reach is planned to a visible or remembered target. To explore the role of PRR in sensorimotor transformations, we tested whether cells would be activated when a reach is planned to an as-yet unspecified goal. Over one-third of PRR cells increased their firing after an instruction to prepare a reach, but not after an instruction to prepare a saccade, when the target of the movement remained unknown. A partially overlapping population (two-thirds of cells) was activated when the monkey was informed of the target location but not the type of movement to be made. Thus a subset of PRR neurons separately code spatial and effector-specific information, consistent with a role in specifying potential motor responses to particular targets.

Eye-hand coordination: saccades are faster when accompanied by a coordinated arm movement.

When primates reach for an object, they very often direct an eye movement toward the object as well. This pattern of directing both eye and limb movements to the same object appears to be fundamental to eye-hand coordination. We investigated interactions between saccades and reaching movements in a rhesus monkey model system. The amplitude and peak velocity of isolated eye movements are positively correlated with one another. This relationship is called the main sequence. We now report that the main sequence relationship for saccades is changed during coordinated eye and arm movements. In particular, peak eye velocity is approximately 4% faster for the same size saccade when the saccade is accompanied by a coordinated arm movement. Saccade duration is reduced by an equivalent amount. The main sequence relationship is unperturbed when the arm moves simultaneously but in the opposite direction as the eyes, suggesting that eye and arm movements must be tightly coordinated to produce the effect. Candidate areas mediating this interaction include the posterior parietal cortex and the superior colliculus.