Jeffrey L. Calton

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.

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 ones 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.

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° 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.

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 rats 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.

Reduction of voltage-dependent currents by ethanol contributes to inhibition of NMDA receptor-mediated excitatory synaptic transmission

Previous studies have shown inhibitory effects of EtOH on NMDA receptor-mediated synaptic transmission in several brain regions. We examined this effect of EtOH under both current clamp and voltage clamp conditions in the basolateral amygdala because of the putative role of the amygdala in mediating anxiolytic effects of EtOH. We found that EtOH reduced NMDA receptor-mediated synaptic responses. In addition, we found that NMDA receptor-mediated depolarizations could also activate a voltage-dependent regenerative potential which was also sensitive to EtOH. Pharmacological characterization of this current was consistent with a high-threshold Ca2+ current. This current also exhibited a pronounced tendency towards transient enhancement upon withdrawal of EtOH.

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.

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.

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.