A novel role for the rat retrosplenial cortex in cognitive control

By virtue of its frontal and hippocampal connections, the retrosplenial cortex is uniquely placed to support cognition. Here, we tested whether the retrosplenial cortex is required for frontal tasks analogous to the Stroop Test, i.e., for the ability to select between conflicting responses and inhibit responding to task-irrelevant cues. Rats first acquired two instrumental conditional discriminations, one auditory and one visual, set in two distinct contexts. As a result, rats were rewarded for pressing either the right or left lever when a particular auditory or visual signal was present. In extinction, rats received compound stimuli that either comprised the auditory and visual elements that signaled the same lever response (congruent) or signaled different lever responses (incongruent) during training. On conflict (incongruent) trials, lever selection by sham-operated animals followed the stimulus element that had previously been trained in that same test context, whereas animals with retrosplenial cortex lesions failed to disambiguate the conflicting response cues. Subsequent experiments demonstrated that this abnormality on conflict trials was not due to a failure in distinguishing the contexts. Rather, these data reveal the selective involvement of the rat retrosplenial cortex in response conflict, and so extend the frontal system underlying cognitive control

Post-training depletions of basolateral amygdala serotonin fail to disrupt discrimination, retention, or reversal learning.

In goal-directed pursuits, the basolateral amygdala (BLA) is critical in learning about changes in the value of rewards. BLA-lesioned rats show enhanced reversal learning, a task employed to measure the flexibility of response to changes in reward. Similarly, there is a trend for enhanced discrimination learning, suggesting that BLA may modulate formation of stimulus-reward associations. There is a parallel literature on the importance of serotonin (5HT) in new stimulus-reward and reversal learning. Recent postulations implicate 5HT in learning from punishment. Whereas, dopaminergic involvement is critical in behavioral activation and reinforcement, 5HT may be most critical for aversive processing and behavioral inhibition, complementary cognitive processes. Given these findings, a 5HT-mediated mechanism in BLA may mediate the facilitated learning observed previously. The present study investigated the effects of selective 5HT lesions in BLA using 5,7-dihydroxytryptamine (5,7-DHT) vs. infusions of saline (Sham) on discrimination, retention, and deterministic reversal learning. Rats were required to reach an 85% correct pairwise discrimination and single reversal criterion prior to surgery. Postoperatively, rats were then tested on the (1) retention of the pretreatment discrimination pair, (2) discrimination of a novel pair, and (3) reversal learning performance. We found statistically comparable preoperative learning rates between groups, intact postoperative retention, and unaltered novel discrimination and reversal learning in 5,7-DHT rats. These findings suggest that 5HT in BLA is not required for formation and flexible adjustment of new stimulus-reward associations when the strategy to efficiently solve the task has already been learned. Given the complementary role of orbitofrontal cortex in reward learning and its interconnectivity with BLA, these findings add to the list of dissociable mechanisms for BLA and orbitofrontal cortex in reward learning

Self-directedness, integration and higher cognition

In this paper I discuss connections between self-directedness, integration and higher cognition. I present a model of self-directedness as a basis for approaching higher cognition from a situated cognition perspective. According to this model increases in sensorimotor complexity create pressure for integrative higher order control and learning processes for acquiring information about the context in which action occurs. This generates complex articulated abstractive information processing, which forms the major basis for higher cognition. I present evidence that indicates that the same integrative characteristics found in lower cognitive process such as motor adaptation are present in a range of higher cognitive process, including conceptual learning. This account helps explain situated cognition phenomena in humans because the integrative processes by which the brain adapts to control interaction are relatively agnostic concerning the source of the structure participating in the process. Thus, from the perspective of the motor control system using a tool is not fundamentally different to simply controlling an arm

Distinct patterns of outcome valuation and amygdala-prefrontal cortex synaptic remodeling in adolescence and adulthood.

Adolescent behavior is typified by increased risk-taking, reward- and novelty-seeking, as well as an augmented need for social and environmental stimulation. This behavioral phenotype may result from alterations in outcome valuation or reward learning. In the present set of experiments, we directly compared adult and adolescent animals on tasks measuring both of these processes. Additionally, we examined developmental differences in dopamine D1-like receptor (D1R), dopamine D2-like receptor (D2R), and polysialylated neural cell adhesion molecule (PSA-NCAM) expression in animals that were trained on an effortful reward valuation task, given that these proteins play an important role in the functional development of the amygdala-prefrontocortical (PFC) circuit and mesocorticolimbic dopamine system. We found that adolescent animals were not different from adults in appetitive associative learning, but exhibited distinct pattern of responses to differences in outcome values, which was paralleled by an enhanced motivation to invest effort to obtain larger rewards. There were no differences in D2 receptor expression, but D1 receptor expression was significantly reduced in the striatum of animals that had experiences with reward learning during adolescence compared to animals that went through the same experiences in adulthood. We observed increased levels of PSA-NCAM expression in both PFC and amygdala of late adolescents compared to adults that were previously trained on an effortful reward valuation task. PSA-NCAM levels in PFC were strongly and positively associated with high effort/reward (HER) choices in adolescents, but not in adult animals. Increased levels of PSA-NCAM expression in adolescents may index increased structural plasticity and represent a neural correlate of a reward sensitive endophenotype

Translational outcomes in a full gene deletion of ubiquitin protein ligase E3A rat model of Angelman syndrome.

Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by developmental delay, impaired communication, motor deficits and ataxia, intellectual disabilities, microcephaly, and seizures. The genetic cause of AS is the loss of expression of UBE3A (ubiquitin protein ligase E6-AP) in the brain, typically due to a deletion of the maternal 15q11-q13 region. Previous studies have been performed using a mouse model with a deletion of a single exon of Ube3a. Since three splice variants of Ube3a exist, this has led to a lack of consistent reports and the theory that perhaps not all mouse studies were assessing the effects of an absence of all functional UBE3A. Herein, we report the generation and functional characterization of a novel model of Angelman syndrome by deleting the entire Ube3a gene in the rat. We validated that this resulted in the first comprehensive gene deletion rodent model. Ultrasonic vocalizations from newborn Ube3am-/p+ were reduced in the maternal inherited deletion group with no observable change in the Ube3am+/p- paternal transmission cohort. We also discovered Ube3am-/p+ exhibited delayed reflex development, motor deficits in rearing and fine motor skills, aberrant social communication, and impaired touchscreen learning and memory in young adults. These behavioral deficits were large in effect size and easily apparent in the larger rodent species. Low social communication was detected using a playback task that is unique to rats. Structural imaging illustrated decreased brain volume in Ube3am-/p+ and a variety of intriguing neuroanatomical phenotypes while Ube3am+/p- did not exhibit altered neuroanatomy. Our report identifies, for the first time, unique AS relevant functional phenotypes and anatomical markers as preclinical outcomes to test various strategies for gene and molecular therapies in AS

The dimensions of personality in humans and other animals: A comparative and evolutionary perspective

This paper considers the structure and proximate mechanisms of personality in humans and other animals. Significant similarities were found between personality structures and mechanisms across species in at least two broad traits: Extraversion and Neuroticism. The factor space tapped by these personality dimensions is viewed as a general integrative framework for comparative and evolutionary studies of personality in humans and other animals. Most probably, the cross-species similarities between the most broad personality dimensions like Extraversion and Neuroticism as well as other Big Five factors reflect conservative evolution: constrains on evolution imposed by physiological, genetic and cognitive mechanisms. Lower-order factors, which are more species- and situation-specific, would be adaptive, reflecting correlated selection on and trade-offs between many traits

Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: studies with the concurrent fixed ratio 5/ chow feeding choice task

Rationale. Effort-related motivational symptoms such as anergia and fatigue are common in patients with depression and other disorders. Research implicates pro-inflammatory cytokines in depression, and administration of cytokines can induce effort-related motivational symptoms in humans. Objectives. The present experiments focused on the effects of the pro-inflammatory cytokine interleukin 1-beta (IL-1β) on effort-related choice behavior. Methods. Rats were tested on a concurrent fixed ratio 5 lever pressing/chow feeding choice procedure, which assesses the tendency of rats to work for a preferred food (high carbohydrate pellets) in the presence of a concurrently available but less preferred substitute (laboratory chow). Results. IL-1β (1.0–4.0 μg/kg IP) shifted choice behavior, significantly decreasing lever pressing and increasing intake of the freely available chow. The second experiment assessed the ability of the adenosine A2A antagonist (E)-phosphoric acid mono-[3-[8-[2-(3-methoxyphenyl)vinyl]-7-methyl-2,6-dioxo-1-prop-2-ynyl-1,2,6,7-tetrahydropurin-3-yl] propyl] ester disodium salt (MSX-3) to reverse the behavioral effects of IL-1β. MSX-3 attenuated the effort-related impairments produced by IL-1β, increasing lever pressing and also decreasing chow intake. In the same dose range that shifted effort-related choice behavior, IL-1β did not alter food intake or preference in parallel free-feeding choice studies, indicating that these low doses were not generally suppressing appetite or altering preference for the high carbohydrate pellets. In addition, IL-1β did not affect core body temperature. Conclusions. These results indicate that IL-1β can reduce the tendency to work for food, even at low doses that do not produce a general sickness, malaise, or loss of appetite. This research has implications for the involvement of cytokines in motivational symptoms such as anergia and fatigue

Psychological factors affecting equine performance

For optimal individual performance within any equestrian discipline horses must be in peak physical condition and have the correct psychological state. This review discusses the psychological factors that affect the performance of the horse and, in turn, identifies areas within the competition horse industry where current behavioral research and established behavioral modification techniques could be applied to further enhance the performance of animals. In particular, the role of affective processes underpinning temperament, mood and emotional reaction in determining discipline-specific performance is discussed. A comparison is then made between the training and the competition environment and the review completes with a discussion on how behavioral modification techniques and general husbandry can be used advantageously from a performance perspective

Motivation - A selected bibliography

Bibliography of publications on motivatio

Neuropsychology of reinforcement processes in the rat

This thesis investigated the role played by regions of the prefrontal cortex and ventral striatum in the control of rats’ behaviour by Pavlovian conditioned stimuli, and in their capacity to choose delayed reinforcement. First, the function of the anterior cingulate cortex (ACC) in simple Pavlovian conditioning tasks was addressed. The ACC is a subdivision of prefrontal cortex that has previously been suggested to be critical for the formation of stimulus–reward associations. It was found that lesions of the ACC did not prevent rats from learning a simple conditioned approach response to a conditioned stimulus (CS) predictive of food reward, or from utilizing that CS as a conditioned reinforcer subsequently. Additionally, these subjects successfully acquired a conditioned freezing response to a CS predicting footshock. However, the same animals were impaired at the acquisition of autoshaped behaviour, an impairment that has been demonstrated previously. An autoshaping deficit was also observed when lesions were made following training. The phenomenon of Pavlovian–instrumental transfer was intact in these subjects. The hypothesis was developed that the ACC is not critical for the formation of stimulus–reward associations per se, but is critical when multiple stimuli must be discriminated on the basis of their differential association with reward. In support of this hypothesis, animals with lesions of the ACC were impaired on a version of the conditioned approach task in which a second, neutral stimulus, perceptually similar to the CS, was added; the lesioned subjects exhibited reduced discrimination. Second, the role of the nucleus accumbens (Acb) in Pavlovian–instrumental transfer was investigated. The nucleus accumbens core, together with a larger amygdalar–striatal network of which it is a component, has previously been shown to be necessary for the expression of ‘simple’ Pavlovian–instrumental transfer. Rats with lesions of the nucleus accumbens core (AcbC) and shell (AcbSh) were tested on a ‘response-specific’ Pavlovian–instrumental transfer task, in which a Pavlovian CS selectively enhances instrumental responding for the outcome with which the CS was originally paired. AcbC lesions impaired the response specificity of this effect, while AcbSh lesions abolished Pavlovian–instrumental transfer entirely. These results are consistent with some — but not all — previous results in suggesting that the shell provides ‘vigour’ and the core provides ‘direction’ for the potentiation of behaviour by Pavlovian CSs. Third, an attempt was made to train rats on a task for assessing preference for delayed reinforcement, using the ‘adjusting-delay’ paradigm. It was not immediately apparent that the rats reacted to the contingencies operative in this task, and mathematical analysis of their behaviour was conducted to establish whether their behaviour was sensitive to the delay, and what ‘molar’ features of performance on this task could be explained by delay-independent processes. Fourth, a different delayed reinforcement choice task was developed, modifying a previously published task in which the subject is repeatedly offered a choice, in discrete trials, of a small reward delivered immediately, and a large reward delivered after a delay, with the delays systematically varied by the experimenter. Rats were trained on versions of this task in which the large, delayed reinforcer was or was not explicitly signalled by a cue present during the delay. The behavioural basis of performance on this task was examined, and d-amphetamine, chlordiazepoxide, and alpha-flupenthixol were administered systemically. It was found that the effects of d-amphetamine depended on whether the delayed reinforcer was signalled or unsignalled, increasing preference for signalled delayed reinforcement at some doses, but decreasing preference for unsignalled delayed reinforcement. These results may resolve contradictions in the literature, and are suggested to reflect the known effect of amphetamine to potentiate responding for conditioned reinforcers. Fifth, rats that had been trained on this task (with no explicit signals present during the delay) were given lesions of the ACC, AcbC, or medial prefrontal cortex (mPFC). ACC-lesioned rats were no different from sham-operated controls in their ability to choose a large, delayed reinforcer. Lesions of mPFC reduced the tendency of subjects to shift from one lever to the other during the course of a session, but mPFC-lesioned subjects responded normally to removal of the delays, suggesting a loss of stimulus control. However, rats with lesions of the AcbC were severely impaired on this task, preferring the small, immediate reward, even though they discriminated the reinforcers. Additionally, the effects of intra-Acb amphetamine were assessed using a different version of the delayed reinforcement choice task, and found to have slight but inconsistent effects to reduce preference for the delayed reinforcer, though this effect did not depend on whether the delayed reward was signalled or unsignalled. These results suggest that the AcbC contributes significantly to the rat’s ability to choose a delayed reward, a finding that has important implications for the understanding of Acb function. It is suggested that dysfunction of the AcbC may be a key element in the pathology of impulsivity.Supported by a UK Medical Research Council (MRC) research studentship, 1997–2000, and a James Baird award, University of Cambridge School of Clinical Medicine, 1997–2000