Summary Neuronal oscillations comprise a fundamental mechanism by which distant neural structures establish and express functional connectivity. Long-range functional connectivity between the hippocampus and other forebrain structures is enabled by theta oscillations. Here we show for the first time that the infant rat red nucleus (RN)—a brainstem sensorimotor structure— exhibits theta (4-7 Hz) oscillations restricted primarily to periods of active (REM) sleep. At postnatal day (P) 8, theta is expressed as brief bursts immediately following myoclonic twitches; by P12, theta oscillations are expressed continuously across bouts of active sleep. Simultaneous recordings from the hippocampus and RN at P12 show that theta oscillations in both structures are coherent, co-modulated, and mutually interactive during active sleep. Critically, at P12, inactivation of the medial septum eliminates theta in both structures. The developmental emergence of theta-dependent functional coupling between the hippocampus and RN parallels that between the hippocampus and prefrontal cortex. Accordingly, disruptions in the early expression of theta could underlie the cognitive and sensorimotor deficits associated with neurodevelopmental disorders such as autism and schizophrenia.

Hippocampal-dependent tasks often involve specific associations among stimuli (including egocentric information), and such tasks are therefore prone to interference from irrelevant task strategies before a correct strategy is found. Using an object-place paired-associate task, we investigated changes in neural firing patterns in the hippocampus in association with a shift in strategy during learning. We used an object-place paired-associate task in which a pair of objects was presented in two different arms of a radial maze. Each object was associated with reward only in one of the arms, thus requiring the rats to consider both object identity and its location in the maze. Hippocampal neurons recorded in CA1 displayed a dynamic transition in their firing patterns during the acquisition of the task across days, and this corresponded to a shift in strategy manifested in behavioral data. Specifically, before the rats learned the task, they chose an object that maintained a particular egocentric relationship with their body (response strategy) irrespective of the object identity. However, as the animal acquired the task, it chose an object according to both its identity and the associated location in the maze (object-in-place strategy). We report that CA1 neurons in the hippocampus changed their prospective firing correlates according to the dominant strategy (i.e., response versus object-in-place strategy) employed at a given stage of learning. The results suggest that neural firing pattern in the hippocampus is heavily influenced by the task demand hypothesized by the animal and the firing pattern changes flexibly as the perceived task demand changes.[Supplemental material is available online at http://www.learnmem.org.]An event often involves objects placed in particular locations. To form a cognitive representation of such an event, an animal needs to represent many heterogeneous pieces of information such as individual objects, their spatial locations, and also egocentric body movements associated with the navigation through the objects and locations. All the information then needs to be associated in a correct way (e.g., proper object-place association) for successful representation of the event. Processing only a subset of information successfully may lead to an error in identifying the correct event. It is believed that the hippocampus is essential for forming and retrieving such conjunctive representations among stimuli for processing events (O'Reilly and McClelland 1994).Due to its conjunctive information processing after receiving inputs from multiple sources (e.g., information for object recognition, egocentric memory, allocentric memory, etc.), the hippocampal system is prone to competition with other systems especially when a simpler strategy that requires information from a single source seems a viable option. Behavioral and pharmacological studies have supported this hypothesis (Packard and McGaugh 1996;Poldrack and Packard 2003). Physiologically, the influence of switching strategy on hippocampal ne...

A prominent theory of category learning, COVIS, posits that new categories are learned with either a declarative or procedural system, depending on the task. The declarative system uses the prefrontal cortex (PFC) to learn rule-based (RB) category tasks in which there is one relevant sensory dimension that can be used to establish a rule for solving the task, whereas the procedural system uses corticostriatal circuits for information integration (II) tasks in which there are multiple relevant dimensions, precluding use of explicit rules. Previous studies have found faster learning of RB versus II tasks in humans and monkeys but not in pigeons. The absence of a learning rate difference in pigeons has been attributed to their lacking a PFC. A major gap in this comparative analysis, however, is the lack of data from a nonprimate mammalian species, such as rats, that have a PFC but a less differentiated PFC than primates. Here, we investigated RB and II category learning in rats. Similar to pigeons, RB and II tasks were learned at the same rate. After reaching a learning criterion, wider distributions of stimuli were presented to examine generalization. A second experiment found equivalent RB and II learning with wider category distributions. Computational modeling revealed that rats extract and selectively attend to category-relevant information but do not consistently use rules to solve the RB task. These findings suggest rats are on a continuum of PFC function between birds and primates, with selective attention but limited ability to utilize rules relative to primates.

Behavioral analyses of the ontogeny of memory have shown that hippocampus-dependent learning emerges relatively late in postnatal development compared with simple associative learning. Maturation of hippocampal mnemonic mechanisms has been hypothesized to underlie the development of the later emerging learning processes. However, the role of hippocampal maturation in learning has not been examined directly. The goal of the present study was to examine developmental changes in hippocampal neuronal coding during acquisition of a hippocampus-dependent learning task. We recorded activity from CA1 pyramidal cells in rat pups while they were trained on trace eyeblink conditioning. Trace eyeblink conditioning is a Pavlovian conditioning task that involves the association of a conditioned stimulus (CS) with an unconditioned stimulus over a stimulus-free trace interval. The inclusion of the trace interval is what makes the task hippocampus dependent. In the present study, rats were trained at 21-23, 24 -26, and 31-33 d of age. Previous research from our laboratory and others shows that trace conditioning begins to emerge during the third postnatal week. The results indicate that hippocampal neurons show a substantial increase in responsiveness to task-relevant events during development. Moreover, there is an age-related increase in the proportion of neurons that respond to a combination of trial events (e.g., CS and trace). Our findings indicate that the developmental emergence of hippocampally mediated learning is related to increases in the strength and complexity of CA1 associative coding.

Categorization is a fundamental cognitive function that organizes our experiences into meaningful “chunks.” This category knowledge can then be generalized to novel stimuli and situations. Multiple clinical populations, including people with Parkinson's disease, amnesia, autism, ADHD and schizophrenia, have impairments in the acquisition and use of categories. Although rodent research is well suited for examining the neural mechanisms underlying cognitive functions, many rodent cognitive tasks have limited translational value. To bridge this gap, we use touchscreens to permit greater flexibility in stimulus presentation and task design, track key dependent measures, and minimize experimenter involvement. Touchscreens offer a valuable tool for creating rodent cognitive tasks that are directly comparable to tasks used with humans. Touchscreen tasks are also readily used with cutting‐edge neuroscientific methods that are difficult to do in humans such as optogenetics, chemogenetics, neurophysiology and calcium imaging (using miniscopes). In this review, we show advantages of touchscreen‐based tasks for studying category learning in rats. We also address multiple factors for consideration when designing category learning tasks, including the limitations of the rodent visual system, experimental design, and analysis strategies.

The hippocampus may play a role in categorization because of the need to differentiate stimulus categories (pattern separation) and to recognize category membership of stimuli from partial information (pattern completion). We hypothesized that the hippocampus would be more crucial for categorization of low-density (few relevant features) stimuli-due to the higher demand on pattern separation and pattern completion-than for categorization of high-density (many relevant features) stimuli. Using a touchscreen apparatus, rats were trained to categorize multiple abstract stimuli into two different categories. Each stimulus was a pentagonal configuration of five visual features; some of the visual features were relevant for defining the category whereas others were irrelevant. Two groups of rats were trained with either a high (dense, n = 8) or low (sparse, n = 8) number of category-relevant features. Upon reaching criterion discrimination (≥75% correct, on 2 consecutive days), bilateral cannulas were implanted in the dorsal hippocampus. The rats were then given either vehicle or muscimol infusions into the hippocampus just prior to various testing sessions. They were tested with: the previously trained stimuli (trained), novel stimuli involving new irrelevant features (novel), stimuli involving relocated features (relocation), and a single relevant feature (singleton). In training, the dense group reached criterion faster than the sparse group, indicating that the sparse task was more difficult than the dense task. In testing, accuracy of both groups was equally high for trained and novel stimuli. However, both groups showed impaired accuracy in the relocation and singleton conditions, with a greater deficit in the sparse group. The testing data indicate that rats encode both the relevant features and the spatial locations of the features. Hippocampal inactivation impaired visual categorization regardless of the density of the category-relevant features for the trained, novel, relocation, and singleton stimuli. Hippocampus-mediated pattern completion and pattern separation mechanisms may be necessary for visual categorization involving overlapping irrelevant features.

Previous studies showed that the anterior cingulate cortex (ACC) plays a role in selective visual attention. The current study further examined the role of the ACC in attention using a visual cuing task with task-relevant and task-irrelevant stimuli. On every trial, two stimuli were presented on the touchscreen; one was task-relevant and the other was task-irrelevant. Rats were trained to attend to the task-relevant stimulus over the task-irrelevant stimulus to determine which side of the touchscreen should be selected for reward. After the rats were well-trained, cannulae targeting the ACC were implanted bilaterally for infusions of PBS or muscimol. When the ACC was functionally intact, high task performance was correlated with the anticipatory touches toward the reward; rats touched the stimulus proximal to the correct side more often, regardless of its task-relevancy. Analysis of the pre-surgery training data showed that rats developed anticipatory touches during training. Linear discriminant analyses of the touches also showed that the touches predict rats’ choices in trials. With muscimol infusions, choice accuracy was impaired and the anticipatory touches toward the correct response location were less frequent. A control experiment, in which there were no irrelevant stimuli, showed no effects of ACC inactivation on choice accuracy or anticipatory touches. These results indicate that the rat ACC plays a critical role in reducing distraction from irrelevant stimuli as well as in guiding attention toward the goal locations.

Hippocampal development is thought to play a crucial role in the emergence of many forms of learning and memory, but ontogenetic changes in hippocampal activity during learning have not been examined thoroughly. We examined the ontogeny of hippocampal function by recording theta and single neuron activity from the dorsal hippocampal CA1 area while rat pups were trained in associative learning. Three different age groups [postnatal days (P)17-19, P21-23, and P24-26] were trained over six sessions using a tone conditioned stimulus (CS) and a periorbital stimulation unconditioned stimulus (US). Learning increased as a function of age, with the P21-23 and P24-26 groups learning faster than the P17-19 group. Age- and learning-related changes in both theta and single neuron activity were observed. CA1 pyramidal cells in the older age groups showed greater task-related activity than the P17-19 group during CS-US paired sessions. The proportion of trials with a significant theta (4–10 Hz) power change, the theta/delta ratio, and theta peak frequency also increased in an age-dependent manner. Finally, spike/theta phase-locking during the CS showed an age-related increase. The findings indicate substantial developmental changes in dorsal hippocampal function that may play a role in the ontogeny of learning and memory.