Behavioral Neuroscience

Concurrent discrimination learning in Parkinson’s disease.
Studies of neuropsychological patients and experimental animals have demonstrated that the striatum plays a role in implicit habit learning. Here, we examined the performance of patients with Parkinson’s disease (PD) on a concurrent discrimination task that can be learned implicitly by neurologically intact individuals. Participants viewed a pair of shapes on each trial and, under a timed deadline, guessed which one concealed a smiling face. About half the control participants exhibited minimal awareness of the cue–reward relationships as assessed by a post-test evaluation. Nevertheless, these participants were able to perform the discrimination task; there was no correlation between awareness and performance on the task. In contrast, minimally aware patients with PD showed no learning, whereas those who were more aware of the relationships performed as well as control participants on the task. There was a significant correlation between awareness and performance in patients with PD. These data support the idea that the basal ganglia play a role in implicit habit learning and underscore the importance of using tests of awareness to assess the content and process of learning in humans. (PsycINFO Database Record (c) 2009 APA, all rights reserved)
Amygdala-dependent fear conditioning in humans is modulated by the BDNFval66met polymorphism.
The brain-derived neurotrophic factor (BDNF) is critically involved in neuroplasticity, as well as the acquisition, consolidation, and retention of hippocampal- and amygdala-dependent learning. A common functional A?G single nucleotide polymorphism (BDNFval66met) in the prodomain of the human BDNF gene is associated with abnormal intracellular trafficking and reduced activity-dependent BDNF release. We studied the effect of BDNFval66met in an aversive differential fear conditioning, and a delayed extinction paradigm in 57 healthy participants. Pictures of male faces were used as stimuli and fear learning was quantified by fear potentiated startle (FPS) and skin conductance responses (SCR). Aware BDNF met-carriers show a deficit in amygdala-dependent fear conditioning as indicated by an absence of FPS responses in the last acquisition block. This deficit was maintained in the first block of extinction. No genotype differences were found in conditioned SCR discrimination. These data provide evidence for the involvement of BDNF signaling in human amygdala-dependent learning. We suggest that the BDNF met-allele may have a protective effect for the development of affective pathologies that may be mediated via reduced synaptic plasticity induced by negative experience. (PsycINFO Database Record (c) 2009 APA, all rights reserved)
Adolescents exhibit behavioral differences from adults during instrumental learning and extinction.
Adolescence is associated with the development of brain regions linked to cognition and emotion. Such changes are thought to contribute to the behavioral and neuropsychiatric vulnerabilities of this period. We compared adolescent (Postnatal Days 28–42) and adult (Postnatal Day 60+) rats as they performed a simple instrumental task and extinction. Rats were trained to poke into a hole for a food-pellet reinforcer. After six days of training, rats underwent extinction sessions in which the previously rewarded behavior was no longer reinforced. During extinction, we examined the effects of continued presentation of a cue light and food restriction. Adults and adolescents exhibited similar performance during training, although adolescents made more task-irrelevant pokes, consistent with increased exploration. Adults made more premature pokes, which could indicate a more exclusive focus on the task. During extinction, adolescents made more perseverative (previously reinforced) pokes than adults. This behavior was strongly modulated by the combination of motivational factors present (food restriction and cue light), indicating that adolescents were differentially sensitive to them. Furthermore, food restriction induced greater open-field activity in adolescents but not in adults. Thus, as the neural circuitry of motivated behavior develops substantially during adolescence, so too does the behavioral sensitivity to motivational factors. Understanding how such factors differently affect adolescents may shed light on mechanisms that lead to the development of disorders that are manifested during this period. (PsycINFO Database Record (c) 2009 APA, all rights reserved)
The role of the nucleus accumbens core in impulsive choice, timing, and reward processing.
The present series of experiments aimed to pinpoint the source of nucleus accumbens core (AcbC) effects on delay discounting. Rats were trained with an impulsive choice procedure between an adjusting smaller sooner reward and a fixed larger later reward. The AcbC-lesioned rats produced appropriate choice behavior when the reward magnitude was equal. An increase in reward magnitude resulted in a failure to increase preference for the larger later reward in the AcbC-lesioned rats, whereas a decrease in the larger later reward duration resulted in normal alterations in choice behavior in AcbC-lesioned rats. Subsequent experiments with a peak timing (Experiments 2 and 3) and a behavioral contrast (Experiment 4) indicated that the AcbC-lesioned rats suffered from decreased incentive motivation during changes in reward magnitude (Experiments 2 and 4) and when expected rewards were omitted (Experiments 2 and 3), but displayed intact anticipatory timing of reward delays (Experiments 2 and 3). The results indicate that the nucleus accumbens core is critical for determining the incentive value of rewards, but does not participate in the timing of reward delays. (PsycINFO Database Record (c) 2009 APA, all rights reserved)
Intra-accumbens infusion of a muscarinic antagonist reduces food intake without altering the incentive properties of food-associated cues.
Previous work has implicated the cholinergic system in modulating feeding behavior; however, its specific function remains unclear. This work aims to characterize potential dissociations between the central cholinergic modulation of the incentive properties of food and food-associated cues, and consummatory behaviors. Three separate experiments demonstrated that intra-accumbens infusion of the muscarinic antagonist scopolamine 3 hr before the testing session significantly decreased food intake. General motor activity in anticipation of food was not diminished. Experiments also showed that scopolamine did not impair operant responding for a food-associated conditioned reinforcer (CR), nor was d-amphetamine potentiation of CR responding altered by scopolamine pretreatment. This study contributes to the growing evidence that goal-seeking behaviors are mediated by a set of neural processes distinct from those governing food reward. (PsycINFO Database Record (c) 2009 APA, all rights reserved)
Lesions of the rat perirhinal cortex spare the acquisition of a complex configural visual discrimination yet impair object recognition.
Rats with perirhinal cortex lesions were sequentially trained in a rectangular water tank on a series of 3 visual discriminations, each between mirror-imaged stimuli. When these same discriminations were tested concurrently, the rats were forced to use a configural strategy to solve the problems effectively. There was no evidence that lesions of the perirhinal cortex disrupted the ability to learn the concurrent configural discrimination task, which required the rats to learn the precise combination of stimulus identity with stimulus placement (“structural” learning). The same rats with perirhinal cortex lesions were also unimpaired on a test of spatial working memory (reinforced T maze alternation), although they were markedly impaired on a new test of spontaneous object recognition. For the recognition test, rats received multiple trials within a single session in which on every trial, they were allowed to explore 2 objects, 1 familiar, the other novel. On the basis of their differential exploration times, rats with perirhinal cortex lesions showed very poor discrimination of the novel objects, thereby confirming the effectiveness of the surgery. The discovery that bilateral lesions of the perirhinal cortex can leave configural (structural) learning seemingly unaffected points to a need to refine those models of perirhinal cortex function that emphasize its role in representing conjunctions of stimulus features. (PsycINFO Database Record (c) 2009 APA, all rights reserved)
Brainstem and hypothalamic regulation of sleep pressure and rebound in newborn rats.
Sleep pressure and rebound comprise the two compensatory or “homeostatic” responses to sleep deprivation. Although sleep pressure is expressed by infant rats as early as postnatal day (P)5, sleep rebound does not appear to emerge until after P11. We reexamined the developmental expression of these sleep-regulatory processes in P2 and P8 rats by depriving them of sleep for 30 min using a cold, arousing stimulus delivered to a cold-sensitive region of the snout. This method effectively increased sleep pressure over the 30-min period (i.e., increases in the number of arousing stimuli presented over time). Moreover, sleep rebound (i.e., increased sleep during the recovery period) is demonstrated for the first time at these ages. Next, we showed that precollicular transections in P2 rats prevent sleep rebound without affecting sleep pressure, suggesting that the brainstem is sufficient to support sleep pressure, but sleep rebound depends on neural mechanisms that lie rostral to the transection. Finally, again in P2 rats, we used c-fos immunohistochemistry to examine neural activation throughout the neuraxis during sleep deprivation and recovery. Sleep deprivation and rebound were accompanied by significant increases in neural activation in both brainstem and hypothalamic nuclei, including the ventrolateral preoptic area and median preoptic nucleus. This early developmental expression of sleep pressure and rebound and the apparent involvement of brainstem and hypothalamic structures in their expression further solidify the notion that sleep–wake processes in newborns—defined at these ages without reference to state-dependent EEG activity—provide the foundation on which the more familiar processes of adults are built. (PsycINFO Database Record (c) 2009 APA, all rights reserved)
Increased GABAergic activity in the region of the pedunculopontine and deep mesencephalic reticular nuclei reduces REM sleep and impairs learning in rats.
Newly formed memories are initially fragile and require consolidation to be transformed into an enduring state. Memory consolidation may occur during increased postlearning REM sleep. REM deprivation during these periods (termed REM sleep windows [RSWs]) impairs subsequent performance. The pedunculopontine nucleus (PPT) and adjacent deep mesencephalic reticular nuclei (DpMe) have been implicated in the generation of REM sleep. Following 24-hr baseline recording, rats were trained on the 2-way avoidance task for 50 trials/day over 2 days and retested on Day 3. EEG was recorded 22 hr after training on training Days 1 and 2. Rats were injected with the GABAB agonist baclofen or saline into the PPT/DpMe region at 0300 to coincide with the start of a known RSW. Based on shuttle performance, saline rats were assigned post hoc to a learning group (LG) that avoided the footshock at least 60% at retest or nonlearning group (NLG) that performed below this criterion. Baclofen-injected rats were not assigned post hoc into separate groups as all rats performed below the learning criterion. PPN/DpMe infusions of the inhibitory GABAB agonist baclofen decreased REM and impaired subsequent memory performance. Normal GABAergic transmission in the PPN/DpMe may be necessary for REM to occur and for the consolidation of incentive learning. (PsycINFO Database Record (c) 2009 APA, all rights reserved)
Dynamic interactions between coupled oscillators within the hamster circadian pacemaker.
Within the mammalian suprachiasmatic nucleus, multiple oscillators interact to coordinate circadian rhythms in behavior and physiology. We have developed a behavioral assay that disassociates central oscillators and allows rigorous study of their formal properties and interactions. Rodents held under 24h light:dark:light:dark (LDLD) cycles display “split” activity rhythms that reflect the reorganization of the central pacemaker into two oscillator groups cycling ~12h apart. After transfer to constant conditions, the two activity components rejoin through a series of transients lasting 2–7 days. Here we analyze fusion dynamics, characterize the underlying oscillator interactions, and assess two influencing factors: phase of transfer and lighting conditions upon transfer. Syrian hamsters were split under LDLD with dimly lit nights and then transferred to constant dim illumination or complete darkness during one of the two daily scotophases. Fusion was influenced by phase of transfer, suggesting that the oscillators split under LDLD exert an asymmetric influence over one another. Transfer to constant dim and dark conditions produced similar overall patterns of fusion, but nevertheless differed in the rejoined state of the system. The present results are discussed within a model wherein oscillators influence one another in a phase-dependent manner. (PsycINFO Database Record (c) 2009 APA, all rights reserved)
Hippocampal lesions impair retention of discriminative responding based on energy state cues.
The present research investigated the hypothesis that the hippocampus is involved with the control of appetitive behavior by interoceptive “hunger” and “satiety” signals. Rats were trained to solve a food deprivation intensity discrimination problem in which stimuli produced by 0-hr and 24-hr food deprivation served as discriminative cues for the delivery of sucrose pellets. For Group 0+, sucrose pellets were delivered at the conclusion of each 4-min session that took place under 0-hr food deprivation, whereas no pellets were delivered during sessions that took place when the rats had been food deprived for 24 hr. Group 24+ received the reverse discriminative contingency (i.e., they received sucrose pellets under 24-hr but not under 0-hr food deprivation). When asymptotic discrimination performance was achieved (indexed by greater incidence of food magazine approach behavior on reinforced compared with nonreinforced sessions), half of the rats in each group received hippocampal lesions, and the remaining rats in each group were designated as sham- or nonlesioned controls. Following recovery from surgery, food deprivation discrimination performance was compared for lesioned and control rats in both Groups 0+ and 24+. Discriminative responding was impaired for rats with hippocampal lesions relative to their controls. This impairment was based largely on elevated responding to nonreinforced food deprivation cues. In addition, hippocampal damage was associated with increased body weight under conditions of ad libitum feeding. The results suggest that the inhibition of appetitive behavior by energy state signals may depend, in part, on the hippocampus. (PsycINFO Database Record (c) 2009 APA, all rights reserved)
Caloric restriction alters seizure disposition and behavioral profiles in seizure-prone (fast) versus seizure-resistant (slow) rats.
Caloric restriction (CR), primarily known for extending life span, has proven anticonvulsant in several seizure models and antiepileptogenic in a strain of inherently seizure susceptible mice. Our animal model consisted of a seizure-prone (Fast) strain that naturally exhibits attention-deficit/hyperactivity disorder (ADHD)-like behaviors and a comparison seizure-resistant (Slow) strain; we evaluated CR’s effect on the typical seizure sensitivities and behavioral profiles of each strain. Fast and Slow rats were fed ad libitum or were calorically restricted to 80% of free-feeding body weight. Rats were then tested in the open field (hyperactivity), Morris water maze (learning and attention), and restraint (impulsivity) paradigms and finally kindled from the amygdala. Ultimately, CR abolished signs of abnormal hyperactivity in the Fast strain and retarded their kindling rates, making it the first manipulation to demonstrate an antiepileptogenic effect in this animal model. CR also shortened seizure durations in fully kindled Slow rats but had no effect on their kindling rates, implying a differential effect of CR on genotype. These results clearly endorse further investigation into the potential benefits of CR for both epilepsy and ADHD. (PsycINFO Database Record (c) 2009 APA, all rights reserved)
Dietary cholesterol impairs memory and memory increases brain cholesterol and sulfatide levels.
Cholesterol and sulfatides play many important roles in learning and memory. To date, our observations about the effects of cholesterol on learning have been assessed during response acquisition; that is, the learning of a new memory. Here, we report for the first time to our knowledge, on the effect of a cholesterol diet on a previously formed memory. Rabbits were given trace conditioning of the nictitating membrane response for 10 days, then fed a 2% cholesterol diet for 8 weeks, and then assessed for memory recall of the initially learned task. We show that dietary cholesterol had an adverse effect on memory recall. Second, we investigated whether dietary cholesterol caused an increase in brain cholesterol and sulfatide levels in four major brain structures (hippocampus, frontal lobe, brainstem, and cerebellum) using a technique for analyzing myelin and myelin-free fractions separately. Although our data confirm previous findings that dietary cholesterol does not directly affect cholesterol and establish that it does not affect sulfatide levels in the brain, these levels did increase rather significantly in the hippocampus and frontal lobe as a function of learning and memory. (PsycINFO Database Record (c) 2009 APA, all rights reserved)
The “good” limb makes the “bad” limb worse: Experience-dependent interhemispheric disruption of functional outcome after cortical infarcts in rats.
Following stroke-like lesions to the sensorimotor cortex in rats, experience with the ipsi-to-lesion (ipsilesional), “nonparetic”, forelimb worsens deficits in the contralesional, “paretic”, forelimb. We tested whether the maladaptive effects of experience with the nonparetic limb are mediated through callosal connections and the contralesional sensorimotor cortex. Adult male rats with proficiency in skilled reaching with their dominant (for reaching) forelimb received ischemic bilateral sensorimotor cortex lesions, or unilateral lesions, with or without callosal transections. After assessing dominant forelimb function (the paretic forelimb in rats with unilateral lesions), animals were trained with their nonparetic/nondominant forelimb or underwent control procedures for 15 days. Animals were then tested with their paretic/dominant forelimb. In animals with unilateral lesions only, nonparetic forelimb training worsened subsequent performance with the paretic forelimb, as found previously. This effect was not found in animals with both callosal transections and unilateral lesions. After bilateral lesions, training the nondominant limb did not worsen function of the dominant limb compared with controls. Thus, the maladaptive effects of training the nonparetic limb on paretic forelimb function depend upon the contralesional cortex and transcallosal projections. This suggests that this experience-dependent disruption of functional recovery is mediated through interhemispheric connections of the sensorimotor cortex. (PsycINFO Database Record (c) 2009 APA, all rights reserved)
Age-associated improvements in cross-modal prepulse inhibition in mice.
Prepulse inhibition (PPI) is an operational measure of sensorimotor gating that is thought to probe preattentional filtering mechanisms. PPI is deficient in several neuropsychiatric disorders, possibly reflecting abnormalities in frontal-cortical-striatal circuitry. Several studies support the predictive validity of animal PPI to model human sensorimotor gating phenomena but only limited studies have addressed the effects of aging. Studies in humans suggest that PPI is improved or unaffected as humans age (>60 years) and does not correlate with cognitive decline in aged populations. Rodent studies to date, however, suggest that PPI declines with age. Here we tested the hypothesis that PPI measures in rodents are sensitive to stimulus modality, with the prediction that intact sensory modalities in aged animals would be predictive of aging-induced increases in PPI. To test our hypothesis, we assessed PPI using acoustic, tactile, and visual prepulses in young (4 month) and old (23 month) C57BL/6N mice. Consistent with data across species, we observed reduced startle reactivity in older mice. Aging effects on PPI interacted significantly with prepulse modality, with deficient acoustic PPI but increased visual and tactile PPI in aged animals. These data are therefore consistent with PPI studies in older humans when controlling for hearing impairments. The results are discussed in terms of 1) cross-species translational validity for mouse PPI testing, 2) the need for startle reactivity differences to be accounted for in PPI analyses, and 3) the utility of cross-modal PPI testing in subjects where hearing loss has been documented. (PsycINFO Database Record (c) 2009 APA, all rights reserved)
Competition between novelty and cocaine conditioned reward is sensitive to drug dose and retention interval.
The conditioned rewarding effects of novelty compete with those of cocaine for control over choice behavior using a place conditioning task. The purpose of the present study was to use multiple doses of cocaine to determine the extent of this competition and to determine whether novelty’s impact on cocaine reward was maintained over an abstinence period. In Experiment 1, rats were conditioned with cocaine (7.5, 20, or 30 mg/kg ip) to prefer one side of an unbiased place conditioning apparatus relative to the other. In a subsequent phase, all rats received alternating daily confinements to the previously cocaine paired and unpaired sides of the apparatus. During this phase, half the rats had access to a novel object on their initially unpaired side; the remaining rats did not receive objects. The ability of novelty to compete with cocaine in a drug free and cocaine challenge test was sensitive to cocaine dose. In Experiment 2, a place preference was established with 10 mg/kg cocaine and testing occurred after 1, 14, or 28 day retention intervals. Findings indicate that choice behaviors mediated by cocaine conditioning are reduced with the passing of time. Taken together, competition between cocaine and novelty conditioned rewards are sensitive to drug dose and retention interval. (PsycINFO Database Record (c) 2009 APA, all rights reserved)
Time-based prospective memory impairment in patients with thalamic stroke.
The role of the thalamus in memory is potentially very complex. However, most studies on the memory impairments of thalamic lesions have focused on retrospective memory, rarely on prospective memory. To explore the effect of thalamic lesions on event-based prospective memory (EBPM) and time-based prospective memory (TBPM), respectively, and to verify the hypothesis that the thalamus is involved in the prospective memory, EBPM and TBPM tasks were administered to 18 thalamic stroke patients and 18 age- and education-matched healthy controls. In the EBPM task, subjects were asked to perform an action whenever particular words were presented. In the TBPM task, subjects were asked to perform an action at certain times. Compared with the performance of healthy controls on EBPM and TBPM tasks (EBPM, 4.3 ± 1.5; TBPM, 5.4 ± 1.0), there was a significant difference in the performance of thalamic stroke patients in the TBPM tasks (2.4 ± 1.6), but no difference was found in EBPM tasks (3.7 ± 1.1). These results may indicate that the thalamus is involved in PM and particularly in TBPM. (PsycINFO Database Record (c) 2009 APA, all rights reserved)
Central vasopressin V1a receptor activation is independently necessary for both partner preference formation and expression in socially monogamous male prairie voles.
The neuropeptide arginine vasopressin (AVP) modulates a variety of species-specific social behaviors. In socially monogamous male prairie voles, AVP acts centrally via vasopressin V1a receptor (V1aR) to facilitate mating induced partner preferences. The display of a partner preference requires at least 2 temporally distinct processes: social bond formation as well as its recall, or expression. Studies to date have not determined in which of these processes V1aR acts to promote partner preferences. Here, male prairie voles were administered intracerebroventricularly a V1aR antagonist (AVPA) at different time points to investigate the role of V1aR in social bond formation and expression. Animals receiving AVPA prior to cohabitation with mating or immediately prior to partner preference testing failed to display a partner preference, while animals receiving AVPA immediately after cohabitation with mating and control animals receiving vehicle at all 3 time points displayed partner preferences. These results suggest that V1aR signaling is necessary for both the formation and expression of partner preferences and that these processes are dissociable. (PsycINFO Database Record (c) 2009 APA, all rights reserved)
Evidence for the use of an internal sense of direction in homing.
Path integration, the ability to maintain a representation of location and direction on the basis of internal cues, is thought to be important for navigation and the learning of spatial relationships. Representations of location and direction in the brain, such as head direction cells, grid cells, and place cells in the limbic system, are thought to underlie navigation by path integration. While this idea is generally consistent with lesion studies, the relationship between such neural activity and behavior has not been studied on a task where animals demonstrably use a path integration strategy. Here we report the development of such a task in rats: by slowly rotating rats before their return to a trial-unique home base, we could show subjects relied on internal cues only to navigate. To illustrate how this task can be combined with recording, we show examples of simultaneously recorded head direction cells in which neural activity is closely related to rats’ homing direction. These results support the notion that rats can navigate by path integration, that this ability depends on head direction cells, and suggest a convenient behavioral paradigm for investigating the neural basis of navigation. (PsycINFO Database Record (c) 2009 APA, all rights reserved)
Electroconvulsive shocks exacerbate the heightened acoustic startle response in stressed rats.
Electroconvulsive therapy (ECT) has been successfully used in the treatment of depression, particularly when the illness is refractory to pharmacological therapy. A recent study has shown that ECT is also effective in reducing both depressive and posttraumatic stress disorder (PTSD) symptoms in patients with major depression (MDD) and co-occurring PTSD. This raises the possibility that ECT might be effective in the treatment of PTSD, a disease whose prevalence has increased substantially in recent years. A characteristic symptom of PTSD is an exaggerated reactivity to startling sounds (acoustic startle response; ASR). In the present study, we investigated the effects of electroconvulsive shocks (ECS) on the ASR, in a rat model of traumatic stress. The animals were subjected to a restraint/tailshock paradigm and then administered ECS. ASR measurements were obtained at several time points following ECS administration. Although ECS had no effect in control rats, it significantly exacerbated the already potentiated ASR in the stressed group. While ECT may prove to be an effective treatment for certain symptoms of co-occurring MDD/PTSD or PTSD alone, it may exacerbate heightened arousal associated with PTSD. (PsycINFO Database Record (c) 2009 APA, all rights reserved)
The sleep-like nature of early mammalian behavioral rhythms: Theoretical comment on Todd et al. (2010).
Early sleep patterns lack several of the major defining physiological criteria used to identify sleep states in adult animals, but many typical aspects of mature sleep can nevertheless be demonstrated at surprisingly early stages of development. In Todd, Gibson, Shaw, & Blumberg (2010), the ability to compensate for enforced sleep deprivation is found to be present already shortly after birth in laboratory rats, an altricial mammalian species. Whereas the brainstem is capable of resisting enforced wakefulness by an increasing “pressure” to fall asleep, “catch-up” replacement of the lost sleep by means of longer subsequent sleep durations requires forebrain participation. This investigation represents an initial foray into the theoretically important area of the ontogeny of homeostatic regulatory mechanisms for behaviorally crucial neurophysiological processes. (PsycINFO Database Record (c) 2009 APA, all rights reserved)

Behavioral Neuroscience - Vol 124, Iss 1