Single neuron activity and theta modulation in the posterior parietal cortex in a visuospatial attention task.

The posterior parietal cortex (PPC) is implicated in directing and maintaining visual attention to locations in space. We hypothesized that the PPC also engages other cognitive processes in the transformation of behaviorally relevant visual inputs into appropriate actions, for example, monitoring of multiple locations, selection of responses to locations in space, and monitoring the outcome of response selections. We recorded single cells and local field potentials in the rat PPC during performance on a novel visuospatial attention (VSA) task that requires visually monitoring locations in space in order to make appropriate stimulus-guided locomotor responses. In each trial, rats attended to four locations on the floor of a maze. A randomly chosen location was briefly illuminated. Approach to the correct target location was followed by food reward. We observed that PPC activity correlated with multiple phases of the VSA task, including monitoring for stimulus onset, detection of a target, spatial location of the target, and target choice. A substantial proportion of cells with behavioral correlates were also modulated by outcome of the trial. Our analyses of local field potentials revealed strong oscillatory rhythms in the theta frequency band, and more than a third of PPC neurons were phase locked to theta oscillations. As in other brain regions, theta power correlated with running speed. Peak theta power was higher in superficial layers than deep layers providing evidence against volume conduction from the hippocampus. In addition, theta power was sensitive to the outcome of a choice. Theta power was significantly higher following incorrect choices compared with correct choices, possibly providing a prediction error signal. Our study provides evidence that the rat PPC has multiple roles in the translation of visual information into appropriate behavioral actions. © 2016 Wiley Periodicals, Inc.

Bidirectional Modulation of Recognition Memory.

Perirhinal cortex (PER) has a well established role in the familiarity-based recognition of individual items and objects. For example, animals and humans with perirhinal damage are unable to distinguish familiar from novel objects in recognition memory tasks. In the normal brain, perirhinal neurons respond to novelty and familiarity by increasing or decreasing firing rates. Recent work also implicates oscillatory activity in the low-beta and low-gamma frequency bands in sensory detection, perception, and recognition. Using optogenetic methods in a spontaneous object exploration (SOR) task, we altered recognition memory performance in rats. In the SOR task, normal rats preferentially explore novel images over familiar ones. We modulated exploratory behavior in this task by optically stimulating channelrhodopsin-expressing perirhinal neurons at various frequencies while rats looked at novel or familiar 2D images. Stimulation at 30-40 Hz during looking caused rats to treat a familiar image as if it were novel by increasing time looking at the image. Stimulation at 30-40 Hz was not effective in increasing exploration of novel images. Stimulation at 10-15 Hz caused animals to treat a novel image as familiar by decreasing time looking at the image, but did not affect looking times for images that were already familiar. We conclude that optical stimulation of PER at different frequencies can alter visual recognition memory bidirectionally. Significance statement: Recognition of novelty and familiarity are important for learning, memory, and decision making. Perirhinal cortex (PER) has a well established role in the familiarity-based recognition of individual items and objects, but how novelty and familiarity are encoded and transmitted in the brain is not known. Perirhinal neurons respond to novelty and familiarity by changing firing rates, but recent work suggests that brain oscillations may also be important for recognition. In this study, we showed that stimulation of the PER could increase or decrease exploration of novel and familiar images depending on the frequency of stimulation. Our findings suggest that optical stimulation of PER at specific frequencies can predictably alter recognition memory.

Age-related decrease in theta and gamma coherence across dorsal ca1 pyramidale and radiatum layers.

In both humans and rodents, aging is linked to impairments in hippocampus dependent learning. Given such deficits, one would expect corresponding changes in hippocampal local field potentials, which represent the integration of multiple inputs onto a given dendritic field within the hippocampus. The current experiment examined coherence of theta and gamma in young and aged rats at sub-millimeter and millimeter distant locations both within and across layers in CA1 of the dorsal hippocampus. The degree to which different dendritic layers show coherent oscillations indicates the uniformity of the inputs and local circuitry, and may form an important element for processing information. Aged rats had lower coherence in all frequency ranges; this was most marked within a layer as the distance between electrodes increased. Notably, unlike younger rats, in the aged rats coherence was not affected by running on the maze. Furthermore, despite the previously reported effects of cholinergic activation on theta frequency and power, there was no effect of the cholinomimetic physostigmine on coherence. These data indicate an age related fragmentation in hippocampal processing that may underlie some of the observed learning and memory deficits.

Automated visual cognitive tasks for recording neural activity using a floor projection maze.

Neuropsychological tasks used in primates to investigate mechanisms of learning and memory are typically visually guided cognitive tasks. We have developed visual cognitive tasks for rats using the Floor Projection Maze(1,2) that are optimized for visual abilities of rats permitting stronger comparisons of experimental findings with other species. In order to investigate neural correlates of learning and memory, we have integrated electrophysiological recordings into fully automated cognitive tasks on the Floor Projection Maze(1,2). Behavioral software interfaced with an animal tracking system allows monitoring of the animal's behavior with precise control of image presentation and reward contingencies for better trained animals. Integration with an in vivo electrophysiological recording system enables examination of behavioral correlates of neural activity at selected epochs of a given cognitive task. We describe protocols for a model system that combines automated visual presentation of information to rodents and intracranial reward with electrophysiological approaches. Our model system offers a sophisticated set of tools as a framework for other cognitive tasks to better isolate and identify specific mechanisms contributing to particular cognitive processes.

Dissociation between dorsal and ventral hippocampal theta oscillations during decision-making.

Hippocampal theta oscillations are postulated to support mnemonic processes in humans and rodents. Theta oscillations facilitate encoding and spatial navigation, but to date, it has been difficult to dissociate the effects of volitional movement from the cognitive demands of a task. Therefore, we examined whether volitional movement or cognitive demands exerted a greater modulating factor over theta oscillations during decision-making. Given the anatomical, electrophysiological, and functional dissociations along the dorsal-ventral axis, theta oscillations were simultaneously recorded in the dorsal and ventral hippocampus in rats trained to switch between place and motor-response strategies. Stark differences in theta characteristics were found between the dorsal and ventral hippocampus in frequency, power, and coherence. Theta power increased in the dorsal, but decreased in the ventral hippocampus, during the decision-making epoch. Interestingly, the relationship between running speed and theta power was uncoupled during the decision-making epoch, a phenomenon limited to the dorsal hippocampus. Theta frequency increased in both the dorsal and ventral hippocampus during the decision epoch, although this effect was greater in the dorsal hippocampus. Despite these differences, ventral hippocampal theta was responsive to the navigation task; theta frequency, power, and coherence were all affected by cognitive demands. Theta coherence increased within the dorsal hippocampus during the decision-making epoch on all three tasks. However, coherence selectively increased throughout the hippocampus (dorsal to ventral) on the task with new hippocampal learning. Interestingly, most results were consistent across tasks, regardless of hippocampal-dependent learning. These data indicate increased integration and cooperation throughout the hippocampus during information processing.

Hippocampal theta, gamma, and theta-gamma coupling: effects of aging, environmental change, and cholinergic activation.

Hippocampal theta and gamma oscillations coordinate the timing of multiple inputs to hippocampal neurons and have been linked to information processing and the dynamics of encoding and retrieval. One major influence on hippocampal rhythmicity is from cholinergic afferents. In both humans and rodents, aging is linked to impairments in hippocampus-dependent function along with degradation of cholinergic function. Cholinomimetics can reverse some age-related memory impairments and modulate oscillations in the hippocampus. Therefore, one would expect corresponding changes in these oscillations and possible rescue with the cholinomimetic physostigmine. Hippocampal activity was recorded while animals explored a familiar or a novel maze configuration. Reexposure to a familiar situation resulted in minimal aging effects or changes in theta or gamma oscillations. In contrast, exploration of a novel maze configuration increased theta power; this was greater in adult than old animals, although the deficit was reversed with physostigmine. In contrast to the theta results, the effects of novelty, age, and/or physostigmine on gamma were relatively weak. Unrelated to the behavioral situation were an age-related decrease in the degree of theta-gamma coupling and the fact that physostigmine lowered the frequency of theta in both adult and old animals. The results indicate that age-related changes in gamma and theta modulation of gamma, while reflecting aging changes in hippocampal circuitry, seem less related to aging changes in information processing. In contrast, the data support a role for theta and the cholinergic system in encoding and that hippocampal aging is related to impaired encoding of new information.

Extensive training and hippocampus or striatum lesions: effect on place and response strategies.

The hippocampus has been linked to spatial navigation and the striatum to response learning. The current study focuses on how these brain regions continue to interact when an animal is very familiar with the task and the environment and must continuously switch between navigation strategies. Rats were trained to solve a plus maze using a place or a response strategy on different trials within a testing session. A room cue (illumination) was used to indicate which strategy should be used on a given trial. After extensive training, animals underwent dorsal hippocampus, dorsal lateral striatum or sham lesions. As expected hippocampal lesions predominantly caused impairment on place but not response trials. Striatal lesions increased errors on both place and response trials. Competition between systems was assessed by determining error type. Pre-lesion and sham animals primarily made errors to arms associated with the wrong (alternative) strategy, this was not found after lesions. The data suggest a qualitative change in the relationship between hippocampal and striatal systems as a task is well learned. During acquisition the two systems work in parallel, competing with each other. After task acquisition, the two systems become more integrated and interdependent. The fact that with extensive training (as something becomes a "habit"), behaviors become dependent upon the dorsal lateral striatum has been previously shown. The current findings indicate that dorsal lateral striatum involvement occurs even when the behavior is spatial and continues to require hippocampal processing.

Hippocampal and striatal dependent navigation: sex differences are limited to acquisition.

Estrogen has been demonstrated to enhance the use of hippocampal-based place learning while reducing the use of striatal-based motor-response strategy (Korol, D.L., Malin, E.L., Borden, K.A., Busby, R.A., & Couper-Leo, J. (2004). Shifts in preferred learning strategy across the estrous cycle in female rats. Horm. Behav. 45, 330-338). Previous research has focused on task acquisition and the switch from a place to motor-response navigation with training. The current paradigm allowed an examination of the interplay between these two systems by having well-trained animals switch strategies "on demand." Female and male Sprague-Dawley rats were taught a motor-response task on a plus maze. The rats were then introduced to a place task and taught to switch, by cue, from the motor-response to place strategy. Finally, the rats were trained to continuously alternate between place and motor-responses strategies. The maze configuration allowed for an analysis of cooperative choices (both strategies result in the same goal arm), competitive choices (both strategies result in different goal arms), and single strategy choices (can only use the motor-response strategy). The results indicate that sex and estrogen-related effects on navigation strategy are limited to the initial stages of learning a task. The role of sex and estrogen is diminished once the task is well learned, and presumably, the relative involvement of the hippocampal and striatal systems is established.