The Interaction of Cue Type and Its Associated Behavioral Response Dissociates the Neural Activity between the Perirhinal and Postrhinal Cortices.

The perirhinal cortex (PER) and postrhinal cortex (POR) in the medial temporal lobe are commonly described as two distinct systems that process nonspatial and spatial information, respectively. Recent findings suggest that the two regions exhibit functional overlap when processing stimulus information, especially when associative responses are required in goal-directed behavior. However, we lack the neural correlates of this. In the current study, we recorded spiking activities for single units of the PER and POR as rats were required to choose a response associated with the identity of a visual object or scene stimulus. We found that similar proportions of cells fired selectively for either scene or object between the two regions. In the PER and POR, response-selective neurons showed higher contrast for different responses than stimulus-selective cells did for stimuli. More cells fired selectively for specific choice response in the POR than in the PER. The differential firing patterns of the PER and POR were best explained when the stimulus and response components were considered together: Stimulus-selective cells were modulated more by the response in the POR than in the PER, whereas response-selective cells in the PER were modulated more by object information than by scenes. Our results suggest that in a goal-directed memory task, the information processing in the PER and POR may be dynamically modulated not only by input stimulus information but also by the associated choice behavior and stimulus-response interaction.

Plasticity of stereotyped birdsong driven by chronic manipulation of cortical-basal ganglia activity.

Cortical-basal ganglia (CBG) circuits are critical for motor learning and performance, and are a major site of pathology. In songbirds, a CBG circuit regulates moment-by-moment variability in song and also enables song plasticity. Studies have shown that variable burst firing in LMAN, the output nucleus of this CBG circuit, actively drives acute song variability, but whether and how LMAN drives long-lasting changes in song remains unclear. Here, we ask whether chronic pharmacological augmentation of LMAN bursting is sufficient to drive plasticity in birds singing stereotyped songs. We show that altered LMAN activity drives cumulative changes in acoustic structure, timing, and sequencing over multiple days, and induces repetitions and silent pauses reminiscent of human stuttering. Changes persisted when LMAN was subsequently inactivated, indicating plasticity in song motor regions. Following cessation of pharmacological treatment, acoustic features and song sequence gradually recovered to their baseline values over a period of days to weeks. Together, our findings show that augmented bursting in CBG circuitry drives plasticity in well-learned motor skills, and may inform treatments for basal ganglia movement disorders.

Goal-directed interaction of stimulus and task demand in the parahippocampal region.

The hippocampus and parahippocampal region are essential for representing episodic memories involving various spatial locations and objects, and for using those memories for future adaptive behavior. The "dual-stream model" was initially formulated based on anatomical characteristics of the medial temporal lobe, dividing the parahippocampal region into two streams that separately process and relay spatial and nonspatial information to the hippocampus. Despite its significance, the dual-stream model in its original form cannot explain recent experimental results, and many researchers have recognized the need for a modification of the model. Here, we argue that dividing the parahippocampal region into spatial and nonspatial streams a priori may be too simplistic, particularly in light of ambiguous situations in which a sensory cue alone (e.g., visual scene) may not allow such a definitive categorization. Upon reviewing evidence, including our own, that reveals the importance of goal-directed behavioral responses in determining the relative involvement of the parahippocampal processing streams, we propose the Goal-directed Interaction of Stimulus and Task-demand (GIST) model. In the GIST model, input stimuli such as visual scenes and objects are first processed by both the postrhinal and perirhinal cortices-the postrhinal cortex more heavily involved with visual scenes and perirhinal cortex with objects-with relatively little dependence on behavioral task demand. However, once perceptual ambiguities are resolved and the scenes and objects are identified and recognized, the information is then processed through the medial or lateral entorhinal cortex, depending on whether it is used to fulfill navigational or non-navigational goals, respectively. As complex sensory stimuli are utilized for both navigational and non-navigational purposes in an intermixed fashion in naturalistic settings, the hippocampus may be required to then put together these experiences into a coherent map to allow flexible cognitive operations for adaptive behavior to occur.

Rhythmic Pruning of Perceptual Noise for Object Representation in the Hippocampus and Perirhinal Cortex in Rats.

Neurons in the temporal cortex signal object familiarity by modulating their spiking activity as the object is repeatedly experienced. However, the neural mechanisms underlying this "repetition effect" and its functional significance remain unknown. We investigated this process in a goal-directed object recognition task in which rats were required to recognize familiar and novel objects. Single-unit spiking activity and local field potential were recorded from the hippocampus and perirhinal cortex (PER) as rats performed the task. Repetition effects were detected in both the hippocampus and PER. However, phase-locking to the theta rhythm was strengthened with object repetitions in the hippocampus but not in the PER, whereas stronger phase-locking was observed with gamma rhythm in the PER but not in the hippocampus. Our findings suggest that the repetition effect occurs in sync with different rhythmic oscillations across different regions and may underlie neural "pruning" of noise that facilitates object recognition.

Interactions between stimulus and response types are more strongly represented in the entorhinal cortex than in its upstream regions in rats.

Previously we reported results which suggested that response types are critical in dissociating the lateral entorhinal cortex (LEC) from the medial entorhinal cortex (MEC) in a scene memory task (Yoo and Lee, 2017). Here, we investigated whether the perirhinal cortex (PER) and postrhinal cortex (POR), the upstream regions of the LEC and MEC, respectively, could be dissociated similarly. We conducted four tasks by combining different stimulus and response types. Our results suggest that the PER is important whenever object recognition is required and, together with prior findings, imply that PER-LEC networks are essential in goal-directed interactions with objects. The POR appears critical for recognizing visual scenes and may play key roles in scene-based navigation together with the MEC. The relative lack of functional dissociation between stimulus and response types at the PER-POR level suggests that actions conditioned on the recognition of external stimuli may be uniquely represented from the EC.

Neural Correlates of Both Perception and Memory for Objects in the Rodent Perirhinal Cortex.

Despite its anatomical positioning as an interface between the perceptual and memory systems, the perirhinal cortex (PER) has long been considered dedicated for object recognition memory. Whether the PER is also involved in object perception has been intensely debated in recent studies, but physiological evidence has been lacking. We recorded single units from the PER while the rat made categorical responses immediately after sampling a visual object as the originally learned objects were ambiguously morphed to varying degrees. Some neurons in the PER  changed their firing rates monotonically following the gradual changes across the morphed objects as if they coded perceptual changes of the object stimuli. However, other neurons abruptly changed their firing rates according to the response categories associated with the morphed objects, seemingly responding to the learned relationships between the stimulus and its associated choice response. The gradual and abrupt changes in object-tuning properties were also found at the neural population level. Furthermore, the object-associated tuning characteristics of neurons in the PER were more readily observable in correct trials than in error trials. Our findings suggest that neurons in the PER represent perceptual details of an object in addition to its mnemonic identity.

Neural correlates of object-associated choice behavior in the perirhinal cortex of rats.

The perirhinal cortex (PRC) is reportedly important for object recognition memory, with supporting physiological evidence obtained largely from primate studies. Whether neurons in the rodent PRC also exhibit similar physiological correlates of object recognition, however, remains to be determined. We recorded single units from the PRC in a PRC-dependent, object-cued spatial choice task in which, when cued by an object image, the rat chose the associated spatial target from two identical discs appearing on a touchscreen monitor. The firing rates of PRC neurons were significantly modulated by critical events in the task, such as object sampling and choice response. Neuronal firing in the PRC was correlated primarily with the conjunctive relationships between an object and its associated choice response, although some neurons also responded to the choice response alone. However, we rarely observed a PRC neuron that represented a specific object exclusively regardless of spatial response in rats, although the neurons were influenced by the perceptual ambiguity of the object at the population level. Some PRC neurons fired maximally after a choice response, and this post-choice feedback signal significantly enhanced the neuronal specificity for the choice response in the subsequent trial. Our findings suggest that neurons in the rat PRC may not participate exclusively in object recognition memory but that their activity may be more dynamically modulated in conjunction with other variables, such as choice response and its outcomes.

Intact CA3 in the hippocampus is only sufficient for contextual behavior based on well-learned and unaltered visual background.

Computational models suggest that the dentate gyrus and CA3 subfields of the hippocampus are responsible for discrete memory representations using pattern separation and pattern completion when a modified external stimulus is recognized as an old memory or encoded as a new memory. Experimental evidence of such computational processes in the hippocampus has been obtained mostly from spatial navigational tasks, and little is known about the proposed computational functions of the hippocampal subfields in "nonspatial" memory tasks. We tested whether rats with major damage in the dentate gyrus induced by colchicine lesions could remember patterned visual scene stimuli presented on LCD screens in the background. Rats responded using a touchscreen to indicate the identity of the visual scene. Performance of the lesion group was normal when tested with familiar visual scenes that had been learned prior to surgery. Lesioned rats exhibited severe deficits in learning novel visual scenes, but eventually reached the same level of performance as controls. However, unlike in controls, novel scene-associated memories formed in the lesion group were unstable and easily disrupted when ambiguous versions of the novel scenes were presented intermixed with the original stimuli. Our findings confirm that the prior computational models can also be applied to the nonspatial memory domain and suggest that the dentate gyrus is not necessary for the retrieval of learned visual scene-associated behavioral responses but plays a crucial role in forming novel visual scene-dependent memory and recognizing altered or ambiguous visual scenes in the background.