Nonspatial sequence coding varies along the CA1 transverse axis.

The hippocampus plays a critical role in the memory for sequences of events, a defining feature of episodic memory. To shed light on the fundamental mechanisms supporting this capacity, we recently recorded neural activity in CA1 as rats performed a nonspatial odor sequence memory task. Our main finding was that, while the animals' location and behavior remained constant, a proportion of CA1 neurons fired differentially to odors depending on whether they were presented in or out of sequence (sequence cells). Here, we further examined if such sequence coding varied along the distal-to-proximal axis of the dorsal CA1 region (distal: toward subiculum; proximal: toward CA3). Differences in information processing along this axis have been suggested by recent anatomical and electrophysiological evidence that odor information may be more strongly represented in the distal segment, whereas spatial information may be more strongly represented in the proximal segment. Recorded neurons were grouped into four arbitrary sections of dorsal CA1, ranging from distal to proximal. We found that, although sequence cell coding was observed across the distal-to-proximal extent of CA1 from which we recorded, it was significantly higher in intermediate CA1, a region with more balanced anatomical input from lateral and medial entorhinal regions. More specifically, in that particular segment of CA1, we observed a significant increase in the magnitude of sequence coding of all cells, as well as in the sequential information content of sequence cells. Importantly, a different pattern was observed when examining the distribution of spatial coding from the same electrodes. Consistent with previous reports, our results suggest that spatial information was more strongly represented in the proximal section of CA1 (higher proportion of cells with place fields). These findings indicate that nonspatial sequence memory coding is not uniformly distributed along the transverse axis of CA1, and that this distribution does not simply follow the expected gradient based on the stimulus modality or the degree of spatial selectivity. Instead, the observed distribution suggests this form of sequence coding may be associated with convergent input from lateral and medial entorhinal regions, which is present throughout the proximodistal axis but greater in intermediate CA1.

Effects of Body Mass Index and Body Fat Percent on Default Mode, Executive Control, and Salience Network Structure and Function.

It is well established that obesity decreases overall life expectancy and increases the risk of several adverse health conditions. Mounting evidence indicates that body fat is likely also associated with structural and functional brain changes, reduced cognitive function, and greater impulsivity. However, previously reported differences in brain structure and function have been variable across studies and difficult to reconcile due to sample population and methodological differences. To clarify these issues, we correlated two independent measures of body composition-i.e., body mass index (BMI) and body fat percent (BFP)-with structural and functional neuroimaging data obtained from a cohort of 32 neurologically healthy adults. Whole-brain voxel-wise analyses indicated that higher BMI and BFP were associated with widespread decreases in gray matter volume, white matter volume, and white matter microstructure (including several regions, such as the striatum and orbitofrontal cortex, which may influence value assessment, habit formation, and decision-making). Moreover, closer examination of resting state functional connectivity, white matter volume, and white matter microstructure throughout the default mode network (DMN), executive control network (ECN), and salience network (SN) revealed that higher BMI and BFP were associated with increased SN functional connectivity and decreased white matter volumes throughout all three networks (i.e., the DMN, ECN, and SN). Taken together, these findings: (1) offer a biologically plausible explanation for reduced cognitive performance, greater impulsivity, and altered reward processing among overweight individuals, and (2) suggest neurobiological mechanisms (i.e., altered functional and structural brain connectivity) that may affect overweight individuals' ability to establish and maintain healthy lifestyle choices.

Dorsolateral striatum implicated in the acquisition, but not expression, of immediate response learning in rodent submerged T-maze.

Animals can use multiple strategies when learning about, and navigating within, their environment. Typically, in the frequently-studied food-rewarded T-maze, rats initially adopt a flexible, hippocampal-dependent place strategy. However, as learning progresses, rats switch to an automatic, striatal-dependent response strategy (Packard & McGaugh, 1996). Interestingly, in a similar but aversively motivating water-submerged T-maze, rats exhibit the opposite behavioral pattern, initially adopting a response strategy but switching to a place strategy with extended training (Asem & Holland, 2013). Here, we examined the effects of transient lidocaine inactivation of the dorsolateral striatum (DLS) on rats' acquisition and expression of place and response strategies in the submerged T-maze. DLS inactivation prior to probe tests had no effect on rats' initial expression of a response strategy nor on their transition to the use of a place strategy with further training. Nevertheless, in a second experiment using the same rats, identical inactivation parameters significantly affected performance in an appetitively motivating positive control task, which required a response strategy. Furthermore, in a third experiment, DLS inactivation prior to early learning trials interfered with the acquisition of the response strategy in the submerged T-maze. These differences in DLS inactivation effects across appetitive and aversive tasks support the view that task motivation plays crucial roles in guiding learning, memory, and behavior. Additionally, differences in DLS inactivation effects between tests of acquisition and expression suggest that the DLS is required during early acquisition but not expression of the response learning strategy.

Dorsolateral striatum is critical for the expression of surprise-induced enhancements in cue associability.

The dorsolateral striatum (DLS) is frequently implicated in sensory-motor integration, including the performance of sensory orienting responses (ORs) and learned stimulus-response habits. Our laboratory previously identified a role for the DLS in rats' performance of conditioned ORs to Pavlovian cues for food delivery. Here, we considered whether DLS is also critical to another aspect of attention in associative learning, the surprise-induced enhancement of cue associability. A large behavioral literature shows that a cue present when an expected event is omitted enters into new associations more rapidly when that cue is subsequently paired with food. Research from our laboratory has shown that both cue associability enhancements and conditioned ORs depend on the function of a circuit that includes the amygdala central nucleus and the substantia nigra pars compacta. In three experiments, we explored the involvement of DLS in surprise-induced associability enhancements, using a three-stage serial prediction task that permitted separation of DLS function in registering surprise (prediction error) and enhancing cue associability, and in using that increased associability to learn more rapidly about that cue later. The results showed that DLS is critical to the expression, but not the establishment, of the enhanced cue associability normally produced by surprise in this task. They extend the role of DLS and the amygdalo-nigro-striatal circuit underlying learned orienting to more subtle aspects of attention in associative learning, but are consistent with the general notion that DLS is more important in the expression of previously acquired tendencies than in their acquisition.

Blocking in autoshaped lever-pressing procedures with rats.

Rats will approach and contact a lever whose insertion into the chamber signals response-independent food delivery. This "autoshaping" or "sign-tracking" phenomenon has recently attracted considerable attention as a platform for studying individual differences in impulsivity, drug sensitization, and other traits associated with vulnerability to drug addiction. Here, we examined two basic stimulus selection phenomena-blocking and overshadowing-in the autoshaped lever pressing of rats. Blocking and overshadowing were decidedly asymmetrical. Previously reinforced lever-extension conditioned stimuli (CSs) completely blocked conditioning to auditory cues (Exps. 1 and 2), and previously nonreinforced lever-extension CSs overshadowed conditioning to auditory cues. By contrast, conditioning to lever-extension CSs was not blocked by either auditory (Exp. 3) or lever-insertion (Exp. 4) cues, and was not overshadowed by auditory cues. Conditioning to a lever-insertion cue was somewhat overshadowed by the presence of another lever, especially in terms of food cup behavior displayed after lever withdrawal. We discuss several frameworks in which the apparent immunity of autoshaped lever pressing to blocking might be understood. Given evidence that different brain systems are engaged when different kinds of cues are paired with food delivery, it is worth considering the possibility that interactions among them in learning and performance may follow different rules. In particular, it is intriguing to speculate that the roles of simple cue-reinforcer contiguity, as well as of individual and aggregate reinforcer prediction errors, may differ across stimulus classes.

Immediate response strategy and shift to place strategy in submerged T-maze.

A considerable amount of research has demonstrated that animals can use different strategies when learning about, and navigating within, their environment. Since the influential research of Packard and McGaugh (1996), it has been widely accepted that, early in learning, rats use a flexible dorsal hippocampal-dependent place strategy. As learning progresses, they switch to a less effortful and more automatic dorsolateral caudate-dependent response strategy. However, supporting literature is dominated by the use of appetitively motivated tasks, using food reward. Because motivation often plays a crucial role in guiding learning, memory, and behavior, we examined spatial learning strategies of rats in an escape-motivated submerged T-maze. In Experiment 1, we observed rapid learning and the opposite pattern as that reported in appetitively motivated tasks. Rats exhibited a response strategy early in learning before switching to a place strategy, which persisted over extensive training. In Experiment 2, we replicated Packard and McGaugh's (1996) observations, using the apparatus and procedures as in Experiment 1, but with food reward instead of water escape. Mechanisms for, and implications of, this motivational modulation of spatial learning strategy are considered.

The effect of high-fat diet on extinction and renewal.

Diets high in saturated fats are linked to health problems and impairments in cognitive function in humans. Recent evidence suggests that exposure to a high-fat diet can impair rats' ability to appropriately inhibit responding to stimuli that are reinforced in some circumstances but not in others. Here, we examined the effects of exposure to a high-fat diet on the context-specific renewal of extinguished responding. Rats first received pairings of a noise stimulus with a food reinforcer. After 14 days of exclusive access to either a high-fat or a matched control diet, rats received nonreinforced presentations (extinction) of the noise in either the same context in which they were trained or a different context. Finally, responding to the noise was evaluated in the original training context in all rats. In control rats, substantial renewal was observed; that is, responding was greater if extinction was conducted in a context different from that of training and testing. Renewal was significantly less robust in rats fed the high-fat diet despite evidence that they were at least as sensitive to context change as control rats. Implications of these results for models of relapse and treatments for phobias, addiction, and overeating are discussed.