Biomedical subjects

Norman M White

Publications and source records attributed to Norman M White.

17 recordsLinked to original sources

PubMed2007

Roles of learning and motivation in preference behavior: mediation by entorhinal cortex, dorsal and ventral hippocampus.

In the latent cue preference (LCP) task, water-deprived rats alternately drink a salt solution in one distinctive compartment of a conditioned cue preference (CCP) apparatus and water in the other compartment over 8 days (training trials). They are then given a choice between the two compartments with no solutions present (preference test). Previous findings showed that this training procedure results in two parallel forms of learning: conditioning to water-paired cues (a water-CCP) and latent learning of an association between salt and salt-paired compartment cues (a salt-LCP). Experiment 1 examined these two types of learning in isolation. Results showed that expression of the salt-LCP required salt deprivation during testing, but expression of the water-CCP did not require a deprivation state during testing. Other results showed that salt-LCP learning itself involves two distinct components: (1) the latent association among neutral cues in the salt-paired compartment, and (2) motivational information about salt deprivation during testing. Previous findings also demonstrated roles for the dorsal hippocampus (DH), ventral hippocampus (VH), and entorhinal cortex (EC) in salt-LCP learning. Experiment 2 examined the involvement of these structures during acquisition or expression of salt-LCP learning. Rats with cannulas aimed at DH, VH, or EC were given infusions of muscimol, either before exposure to the salt-paired, but not the water-paired, compartment during training or before the preference test. Inactivation of the DH or EC impaired both acquisition and expression of the association between salt and salt-paired compartment cues, while inactivation of the VH disrupted the influence of motivational information about salt deprivation required to express the salt-LCP. These results suggest unique roles for the EC-DH circuit and VH in salt-LCP learning, as well as a functional dissociation between the DH and VH.

Animals↗

PubMed2006

Neural circuits mediating latent learning and conditioning for salt in the rat.

Male Long-Evans rats alternately drank a salt solution in one distinctive compartment of a conditioned cue preference (CCP) apparatus and water in a different compartment over 8 days (training trials) and were then given a choice between the two compartments with no solutions present (test trial). Rats that were water deprived during training, then salt+water deprived during testing, spent more time in their salt-paired compartments, a salt latent cue preference (LCP). Rats that were water-only deprived during training and testing spent more time in their water-paired compartments, a water CCP. Rats that were salt+water deprived during both training and testing spent more time in their salt-paired compartments, a salt CCP. Bilateral, pre-training lesions of the lateral amygdala impaired the water and salt CCPs but not the salt LCP, reflecting the role of the amygdala in Pavlovian conditioning. Lesions of the dorsal or ventral hippocampus impaired the salt LCP and the water and salt CCPs, possibly reflecting the role of the hippocampus in contextual learning. Lesions of the fimbria-fornix impaired the water and salt CCPs but not the salt LCP, while lesions of the entorhinal cortex impaired the salt LCP but not the CCPs. This suggests that the LCP depends on a circuit that includes dorsal and ventral hippocampus and entorhinal cortex, a major conduit of sensory information from the cortex. In contrast, the CCPs depend on the amygdala and a circuit that includes the hippocampus and fimbria-fornix, possibly as a conduit of motivational information from subcortical structures.

Amygdala↗

PubMed2006

Cooperation and competition between the dorsal hippocampus and lateral amygdala in spatial discrimination learning.

The conditioned cue preference (CCP) was used to study how rats discriminate between adjacent arms on a radial maze. Chai and White (Behav Neurosci 2004, 118:770-784) showed that an intact dorsal hippocampus is required to learn this discrimination and that an amygdala-based conditioned approach response that produces an equal tendency to enter both arms is simultaneously acquired. In the present experiments, rats were preexposed to the maze with no food and trained by alternately confining them at the ends of two adjacent arms, one that contained food and one that did not. When given a choice between these arms with no food present, the rats spent more time on their food-paired arms, suggesting they had learned to discriminate their locations. Temporary inactivation of the dorsal hippocampus with muscimol during confinement on the food-paired arm had no effect on the discrimination, but inactivation while on the no-food arm impaired it. This pattern of effects was reversed in rats with amygdala lesions (inactivation on the food-paired arm impaired, but inactivation on the no-food arm had no effect on the discrimination), showing that hippocampus-based and amygdala-based learning interact to influence the behavior of normal rats in this situation. The dorsal hippocampus learns about locations that contain food and about locations that do not contain food. The amygdala-based tendency to enter the food-paired arm cooperates with hippocampus-based foraging for food on the food-paired, but the amygdala-based tendency to enter the no-food arm competes with hippocampus-based learning about the absence of food on that arm.

Amygdala↗

PubMed2005

A latent cue preference based on sodium depletion in rats.

Three experiments show latent (or incidental) learning of salt-cue relationships using a conditioned cue-preference paradigm. Rats drank a salt solution while confined in one compartment and water in an adjacent, distinct compartment on alternate days. When given access to the two compartments with no solutions present, sodium-deprived rats preferred their salt-paired compartments; normal rats preferred their water-paired compartments. Reversing the deprivation states of the two groups reversed their preferences. These results show that rats can latently acquire associations between environmental cues and the taste of salt, and can use this information flexibly to guide behavior based upon internal cues produced by sodium deprivation.

Animals↗

PubMed2005

Inactivation of the dorsal hippocampus does not affect learning during exploration of a novel environment.

The conditioned cue preference (CCP) task was used to study the ability of rats to discriminate between spatial locations. Food-deprived rats explored an eight-arm radial maze with no food present (pre-exposure). On subsequent days, they were alternately confined in one arm of the maze with food and in another arm with no food (training), followed by a preference test with no food present, to determine if they had learned to discriminate between the two arm locations. No injections were given during the two latter phases. With adjacent radial maze arms, rats given three 10-min pre-exposure sessions and four food-pairing trials exhibited a preference for their food-paired arms; rats not pre-exposed did not exhibit this preference. Rats pre-exposed 30 min after dorsal hippocampus injections of muscimol exhibited the preference. With widely separated maze arms, rats given two training trials with no pre-exposure exhibited a preference for the food-paired arm; rats that were given one pre-exposure session did not. Rats pre-exposed 30 min after dorsal hippocampus injections of muscimol did not exhibit the preference. The same intrahippocampal muscimol injections that failed to affect the influence of pre-exposure on CCP learning with both arm configurations impaired win-shift performance, a standard test of spatial learning. These findings suggest that a functional dorsal hippocampus is not required for the (incidental or latent) learning that occurs during unreinforced exploration of a novel environment. The information acquired during this activity subsequently produces a latent learning effect if it is used to discriminate between two ambiguous locations (adjacent arms) or a latent inhibition--like effect if it is used to discriminate between two unambiguous locations (separated maze arms).

Animals↗

PubMed2005

Learning the morphine conditioned cue preference: cue configuration determines effects of lesions.

The morphine conditioned cue preference was investigated using two different apparatus configurations. In one configuration, with a clear Plexiglas partition separating the drug-paired and unpaired compartments, rats could see the cues in both compartments while in either one. In the other configuration, with an opaque wood partition separating the two compartments, rats could see the cues in only one compartment at a time. The experiment had three phases: a session of pre-exposure to the entire apparatus; four 2-day training trials during each of which rats received pairings of 5 mg/Kg morphine sulphate with one compartment and saline with the other (compartments and order counterbalanced), and a test session in which the undrugged rats moved freely between the compartments while the time spent in each was measured. Four groups of rats were trained using the opaque partition in all three phases. Normal rats and rats with amygdala or nucleus accumbens lesions exhibited preferences for their morphine-paired compartments; rats with fimbria-fornix lesions had no preferences. Four additional groups were trained using the clear partition during pre-exposure, the opaque partition during training and the clear partition during testing. Normal rats and rats with fimbria-fornix lesions exhibited preferences, rats with amygdala or nucleus accumbens lesions had no preferences. This interaction between lesioned structures and the apparatus configuration is accounted for by the idea that different types of learning produced the preference for morphine-paired cues in the two apparatus configurations. Each type was learned in a different memory system and so was impaired by different lesions. These findings contribute to understanding the nature of the learning processes that produce the morphine CCP.

Amygdala↗

PubMed2005

How independent are parallel memory systems? A theoretical comment on Gibson and Shettleworth (2005).

Using only behavioral manipulations, B. M. Gibson and S. J. Shettleworth (2005) have shown that rats can simultaneously acquire both place and response information. Experiments in which these 2 kinds of information are presented sequentially (response followed by place), provide some evidence for blocking of place learning, suggesting an influence of information acquired by a response-learning system on the subsequent acquisition of information by a place-learning system. A detailed examination of the results in the context of information about the kinds of learning that take place on a maze suggests that the memory processes underlying the rats' behavior in this experiment were considerably more complex than is acknowledged by Gibson and Shettleworth. The discussion illustrates the importance of considering both behavioral and physiological information for understanding how learning and memory functions are organized in the brain.

Animals↗

PubMed2004

Intra-amygdala muscimol injections impair freezing and place avoidance in aversive contextual conditioning.

Rats were trained by shocking them in a closed compartment. When subsequently tested in the same closed compartment with no shock, normal rats showed an increased tendency to freeze. They also showed an increased tendency to actively avoid the compartment when given access to an adjacent neutral compartment for the first time. Amygdala inactivation with bilateral muscimol injections before training attenuated freezing and eliminated avoidance during the test. Rats trained in a normal state and given intra-amygdala muscimol injections before the test did not freeze or avoid the shock-paired compartment. This pattern of effects suggests that amygdala inactivation during training impaired acquisition of a conditioned response (CR) due either to inactivation of a neural substrate essential for its storage or to elimination of a memory modulation effect that facilitates its storage in some other brain region(s). The elimination of both freezing and active avoidance by amygdala inactivation during testing suggests that neither of these behaviors is the CR. The possibility that the CR is a set of internal responses that produces both freezing and avoidance as well as other behavioral effects is discussed.

Amygdala↗

PubMed2004

Amygdala c-Fos induction corresponds to unconditioned and conditioned aversive stimuli but not to freezing.

These experiments examined the relationship between freezing and c-Fos expression in the amygdala. In Experiment 1 freezing was elevated during a period immediately following shock in rats that remained in the shock context, but not in rats that were moved to a different, neutral context. The two groups showed equally elevated c-Fos levels in both the central (CeA) and lateral (LA) nuclei. In Experiment 2 rats were shocked in one compartment (paired) and not shocked in another, distinct compartment (unpaired). Rats re-exposed to the paired compartment 24h later froze more than rats exposed to the unpaired compartment, and rats in both groups froze more than un-shocked rats. c-Fos protein expression in CeA, LA and basolateral (BLA) nucleus was elevated in the rats exposed to the paired compartment but not in rats exposed to the unpaired compartment. Thus, c-Fos expression was induced by exposure to both unconditioned and conditioned stimuli, although it is unclear if the same cell population was activated in both cases. Neither case of c-Fos expression coincided with the occurrence of freezing. c-Fos expression may represent neural activity in LA and CeA produced by exposure to unconditioned cues and activity in BLA, LA and CeA produced by conditioned cues. This activity may contribute to an aversive affective state (or "fear"). Behaviors promoted by this state, such as freezing, may be mediated in other brain areas, or by other neurons in the amygdala.

Acetylcholinesterase↗

PubMed2004

The role of stimulus ambiguity and movement in spatial navigation: a multiple memory systems analysis of location discrimination.

This paper reviews recent findings about how rats navigate by learning to discriminate among locations. The assumption underlying the experiments and their interpretation is that the information required to do this is learned by three independent, parallel memory systems. One system processes cognitive information (or "knowledge"), a second system processes reinforced stimulus-response associations and a third processes Pavlovian conditioned responses in the form of stimulus-affect associations. The information stored in each system produces behavior that, in some cases, results in a location discrimination. The present experiments focus on three factors that influence what each system learns and whether the resulting memory produces behavior that results in a location discrimination. One factor is whether the locations to be discriminated can be identified by unique, unambiguous stimuli or whether they are ambiguously associated with the same stimuli. The second factor is whether the stimuli are observed passively or whether the rats move among them, voluntarily or involuntarily. The third factor is whether or not the rats perform specific reinforced responses in the presence of the stimuli. Instances of co-operative behavioral outputs from memory systems that facilitate location discriminations and of competitive outputs that impede discriminations are described.

Animals↗

PubMed2004

Amygdala inactivation blocks expression of conditioned memory modulation and the promotion of avoidance and freezing.

Rats were exposed to shock-paired cues immediately after training on an appetitive preference task. Elevated levels of freezing in and active avoidance of the shock-paired compartment were observed, and memory for the appetitive task was improved when tested 24 hr later. Intra-amygdala muscimol injected before the posttraining exposure eliminated freezing, avoidance, and memory modulation. The blockade of both freezing and active avoidance, which involve competing behavioral tendencies, makes it unlikely that the amygdala itself generates either behavior. The elimination of conditioned memory modulation suggests that conditioned neurohormonal responses were blocked. These conditioned internal responses may comprise the intervening variable of "conditioned fear" and may promote observable behaviors, the form of which is determined by the environment in which they occur.

Amygdala↗

PubMed2004

Effects of fimbria-fornix, hippocampus, and amygdala lesions on discrimination between proximal locations.

The conditioned cue preference (CCP) task was used to study the information required to discriminate between spatial locations defined by adjacent arms of an 8-arm radial maze. Normal rats learned the discrimination after 3 unreinforced preexposure (PE) sessions and 4 food paired-unpaired training trials. Fimbria-fornix lesions made before, but not after, PE, and hippocampus lesions made at either time, blocked the discrimination, suggesting that the 2 structures processed different information. Lateral amygdala lesions made before PE facilitated the discrimination. This amygdala-mediated interference with the discrimination was the result of a conditioned approach response that did not discriminate between the 2 arm locations. A hippocampus/fimbria-fornix system and an amygdala system process different information about the same learning situation simultaneously and in parallel.

Amygdala↗

PubMed2003

Mnemonic functions of dorsal striatum and hippocampus in aversive conditioning.

These experiments examined the mnemonic functions of hippocampus and dorsal striatum in Pavlovian aversive conditioning. Rats were trained in a single session by presenting three paired tones and footshocks. Immediately after training, they were given microinjections of D-amphetamine or vehicle into either dorsal hippocampus or dorsal striatum. Twenty-four hours later conditioned freezing (measured as cessation of movement by infrared motion detectors) to the experimental context and to the tone were measured separately. Compared to vehicle injections, amphetamine injections into dorsal hippocampus significantly increased conditioned freezing to the context but not to the tone. Injections into dorsal striatum increased conditioned freezing to both the context and the tone. These results converge with findings from lesion experiments suggesting that hippocampus is involved in aversive conditioning with contextual CSs only, and that dorsal striatum is involved in aversive conditioning with both contextual and discrete cue CSs. The functions of the these two structures in relation to that of the amygdala in the mediation of conditioned freezing are discussed.

Amphetamine↗

PubMed2003

Involuntary, unreinforced (pure) spatial learning is impaired by fimbria-fornix but not by dorsal hippocampus lesions.

Pure spatial learning occurs when rats acquire information about an environment while exploring it in the absence of reinforcers. We previously reported that voluntary, unreinforced exploration of a radial maze retards subsequent reinforced conditioned cue preference (CCP) learning in the same maze. In the present experiment, we examined the effects of involuntary, unreinforced pre-exposure to a radial maze. During pre-exposure, rats were moved by an experimenter between the ends of two arms of a radial maze five times in 30 min. This form of pre-exposure retarded CCP learning, whereas rats that were not pre-exposed and rats that were pre-exposed to a maze in a different room displayed normal CCP learning. These findings suggest that some information specific to the maze environment was acquired during involuntary unreinforced pre-exposure to it. In experiment 2, the retardation of reinforced CCP learning by involuntary unreinforced pre-exposure was eliminated by fimbria-fornix lesions made before pre-exposure but was unaffected by fimbria-fornix lesions made after pre-exposure but before training. Large neurotoxic lesions of the dorsal hippocampus made before pre-exposure had no effect on the retardation of CCP learning, but the rats with these lesions were impaired on a standard test of reinforced spatial learning in a water maze. The lesion effects in experiment 2 are similar to those previously reported for voluntary exploration and suggest that pure spatial learning may occur during both voluntary exploration of and involuntary exposure to an environment in the absence of reinforcers. Pure spatial learning can apparently occur with exposure to two different locations within an environment, but the rats do not have to move between the locations voluntarily. An intact fimbria-fornix is required for acquisition but not expression of this form of learning. The hippocampus is not involved in this form of learning.

Animals↗

PubMed2002

Multiple parallel memory systems in the brain of the rat.

A theory of multiple parallel memory systems in the brain of the rat is described. Each system consists of a series of interconnected neural structures. The "central structures" of the three systems described are the hippocampus, the matrix compartment of the dorsal striatum (caudate-putamen), and the amygdala. Information, coded as neural signals, flows independently through each system. All systems have access to the same information from situations in which learning occurs, but each system is specialized to represent a different kind of relationship among the elements (stimulus events, responses, reinforcers) of the information that flows through it. The speed and accuracy with which a system forms a coherent representation of a learning situation depend on the correspondence between the specialization of the system and the relationship among the elements of the situation. The coherence of these stored representations determines the degree of control exerted by each system on behavior in the situation. Although they process information independently the systems interact in at least two ways: by simultaneous parallel influence on behavioral output and by directly influencing each other. These interactions can be cooperative (leading to similar behaviors) or competitive (leading to different behaviors). Experimental findings consistent with these ideas, mostly from experiments with rats, are reviewed.

Amygdala↗

PubMed2002

Conditioned memory modulation, freezing, and avoidance as measures of amygdala-mediated conditioned fear.

Three conditioned aversive responses were used to infer the existence of an unobservable central state of "conditioned fear," and the roles of certain amygdala subregions in producing these responses were investigated. Rats received tone-shock pairings in one compartment of a shuttle box and no tones or shocks in the other, distinctive, compartment. They were then trained to find food in one arm of a Y-maze. After the final training trial they were exposed to different sets of stimuli in the shuttle box with no shock. Twenty-four hours later rats that had received immediate posttraining exposure to the conditioned stimuli (in the shock-paired compartment) made significantly more correct responses on the Y-maze than rats that had been exposed to the neutral stimuli (in the no-shock compartment) or rats that had received delayed posttraining exposure to the conditioned stimuli. This constitutes a demonstration of posttraining memory modulation by conditioned aversive stimuli. Freezing increased during posttraining exposure to the conditioned stimuli compared to the neutral stimuli. When subsequently allowed to move freely between the two compartments, the rats in all groups also showed significant conditioned avoidance of the compartment containing the conditioned stimuli. In a second experiment the effects of lesions confined to specific parts of the amygdala on the three conditioned responses (memory modulation, freezing, avoidance) were tested. Lesions of the central nucleus impaired all three conditioned responses; lesions of the medial nucleus impaired conditioned modulation and avoidance. These lesions had no effect on freezing during the training trials. Lesions of the lateral and basolateral nuclei attenuated freezing during both training and testing. The findings suggest that the central and medial nuclei of the amygdala may be important parts of neural circuits mediating conditioned responses that constitute conditioned aversive states, but that conditioned freezing may be mediated independently.

Acoustic Stimulation↗

PubMedDate not supplied

Dorsal hippocampus function in learning and expressing a spatial discrimination.

Learning to discriminate between spatial locations defined by two adjacent arms of a radial maze in the conditioned cue preference paradigm requires two kinds of information: latent spatial learning when the rats explore the maze with no food available, and learning about food availability in two spatial locations when the rats are then confined in one arm with food and the other with no food. Previous research showed that a functional dorsal hippocampus is not required for latent learning. The present experiments show that it is required for learning about food availability, and during retrieval of both types of information.

Analysis of Variance↗