(1/278) Neural encoding in orbitofrontal cortex and basolateral amygdala during olfactory discrimination learning.

Orbitofrontal cortex (OFC) is part of a network of structures involved in adaptive behavior and decision making. Interconnections between OFC and basolateral amygdala (ABL) may be critical for encoding the motivational significance of stimuli used to guide behavior. Indeed, much research indicates that neurons in OFC and ABL fire selectively to cues based on their associative significance. In the current study recordings were made in each region within a behavioral paradigm that allowed comparison of the development of associative encoding over the course of learning. In each recording session, rats were presented with novel odors that were informative about the outcome of making a response and had to learn to withhold a response after sampling an odor that signaled a negative outcome. In some cases, reversal training was performed in the same session as the initial learning. Ninety-six of the 328 neurons recorded in OFC and 60 of the 229 neurons recorded in ABL exhibited selective activity during evaluation of the odor cues after learning had occurred. A substantial proportion of those neurons in ABL developed selective activity very early in training, and many reversed selectivity rapidly after reversal. In contrast, those neurons in OFC rarely exhibited selective activity during odor evaluation before the rats reached the criterion for learning, and far fewer reversed selectivity after reversal. The findings support a model in which ABL encodes the motivational significance of cues and OFC uses this information in the selection and execution of an appropriate behavioral strategy.  (+info)

(2/278) 7-Nitro indazole, a selective neuronal nitric oxide synthase inhibitor in vivo, impairs spatial learning in the rat.

Nitric oxide (NO) is an intercellular messenger that has been suggested to have a role in learning and memory formation. Previous studies with nonselective NO synthase inhibitors have produced contradictory results in learning experiments. However, these drugs also produced blood pressure changes, as NO is an endothelial-derived relaxing factor. A novel NO synthase inhibitor, 7-nitro indazole (7-NI), as a dose (30 mg/kg i.p.) shown previously to inhibit neuronal NO synthase by 85% without affecting blood pressure, produced amnesic effects both in a water maze and in an 8-arm radial maze. Latency as well as distance was greater in the 7-NI group in the water maze while swim speed was not affected. Latency, working memory (WM), and reference memory (RF) errors were also higher in the 7-NI group in the 8-arm maze. At the end of the second training day, these differences were no longer apparent. However, on the fourth training day, a transfer test in the water maze showed that 7-NI had produced a spatial memory deficit, reducing quadrant bias and the number of annulus crossings. Learning of a visual cue task was not affected. No difference between groups was visible in an open field test. We conclude that neuronal NO synthase activity plays a role in learning and memory formation in the rat.  (+info)

(3/278) Value transmission in discrimination learning involving stimulus chains.

Rats learned a series of reversals of a positional discrimination in which responses to one lever led to delayed food and responses to a second lever led to no food. Interpolated within the delays leading to the different outcomes were two-link stimulus chains. The pairing of each stimulus element with the delayed outcome of food or no food varied across reversals. Either stimulus element could have the same correlation with outcome as occurred on the preceding reversal or the opposite correlation as on the preceding reversal. New reversals were acquired more quickly when both stimulus elements had the same status as during the preceding reversal, and were acquired most slowly when both stimulus elements had the opposite status as that of the preceding reversal. The rate of learning was intermediate when only one of the stimulus elements had the same status as that during the preceding reversal. All of the data are compatible with an interpretation in terms of backward chaining of stimulus value.  (+info)

(4/278) Medial frontal cortex mediates perceptual attentional set shifting in the rat.

If rodents do not display the behavioral complexity that is subserved in primates by prefrontal cortex, then evolution of prefrontal cortex in the rat should be doubted. Primate prefrontal cortex has been shown to mediate shifts in attention between perceptual dimensions of complex stimuli. This study examined the possibility that medial frontal cortex of the rat is involved in the shifting of perceptual attentional set. We trained rats to perform an attentional set-shifting task that is formally the same as a task used in monkeys and humans. Rats were trained to dig in bowls for a food reward. The bowls were presented in pairs, only one of which was baited. The rat had to select the bowl in which to dig by its odor, the medium that filled the bowl, or the texture that covered its surface. In a single session, rats performed a series of discriminations, including reversals, an intradimensional shift, and an extradimensional shift. Bilateral lesions by injection of ibotenic acid in medial frontal cortex resulted in impairment in neither initial acquisition nor reversal learning. We report here the same selective impairment in shifting of attentional set in the rat as seen in primates with lesions of prefrontal cortex. We conclude that medial frontal cortex of the rat has functional similarity to primate lateral prefrontal cortex.  (+info)

(5/278) Impaired social response reversal. A case of 'acquired sociopathy'.

In this study, we report a patient (J.S.) who, following trauma to the right frontal region, including the orbitofrontal cortex, presented with 'acquired sociopathy'. His behaviour was notably aberrant and marked by high levels of aggression and a callous disregard for others. A series of experimental investigations were conducted to address the cognitive dysfunction that might underpin his profoundly aberrant behaviour. His performance was contrasted with that of a second patient (C.L.A.), who also presented with a grave dysexecutive syndrome but no socially aberrant behaviour, and five inmates of Wormwood Scrubs prison with developmental psychopathy. While J.S. showed no reversal learning impairment, he presented with severe difficulty in emotional expression recognition, autonomic responding and social cognition. Unlike the comparison populations, J.S. showed impairment in: the recognition of, and autonomic responding to, angry and disgusted expressions; attributing the emotions of fear, anger and embarrassment to story protagonists; and the identification of violations of social behaviour. The findings are discussed with reference to models regarding the role of the orbitofrontal cortex in the control of aggression. It is suggested that J.S.'s impairment is due to a reduced ability to generate expectations of others' negative emotional reactions, in particular anger. In healthy individuals, these representations act to suppress behaviour that is inappropriate in specific social contexts. Moreover, it is proposed that the orbitofrontal cortex may be implicated specifically either in the generation of these expectations or the use of these expectations to suppress inappropriate behaviour.  (+info)

(6/278) An olfactory discrimination procedure for mice.

This paper describes an olfactory discrimination procedure for mice that is inexpensively implemented and leads to rapid discrimination learning. Mice were first trained to dig in small containers of sand to retrieve bits of buried chocolate. For discrimination training, two containers were presented simultaneously for eight trials per session. One container held sand mixed with cinnamon, and the other held sand mixed with nutmeg. Both containers were baited with chocolate buried in the sand. One odor was designated S+, and mice were allowed to dig and retrieve the chocolate from this container. The other odor was S-, and both containers were removed immediately if subjects began to dig in an S- container. After meeting a two-session acquisition criterion, subjects were given a series of discrimination reversals. In Experiment 1, 12 Swiss-Webster mice (6 male and 6 female) acquired the olfactory discrimination in three to five sessions and completed 3 to 10 successive discrimination reversals within a 50-session testing limit. In Experiment 2, subjects were 14 Pah(enu2) mice, the mouse mutant for phenylketonuria; 7 were homozygotes in which the disorder was expressed (PKU), and 7 were heterozygotes with normal metabolism (non-PKU). Thirteen mice completed pretraining in four to seven sessions, acquisition required 3 to 12 sessions, and all mice completed at least three reversals. Learning rates were similar in PKU and non-PKU mice. We discuss issues related to implementation and several potentially useful procedural variations.  (+info)

(7/278) Substratal idiothetic navigation of rats is impaired by removal or devaluation of extramaze and intramaze cues.

The spatial orientation of vertebrates is implemented by two complementary mechanisms: allothesis, processing the information about spatial relationships between the animal and perceptible landmarks, and idiothesis, processing the substratal and inertial information produced by the animal's active or passive movement through the environment. Both systems allow the animal to compute its position with respect to perceptible landmarks and to the already traversed portion of the path. In the present study, we examined the properties of substratal idiothesis deprived of relevant exteroceptive information. Rats searching for food pellets in an arena formed by a movable inner disk and a peripheral immobile belt were trained in darkness to avoid a 60 degrees sector; rats that entered this sector received a mild foot shock. The punished sector was defined in the substratal idiothetic frame, and the rats had to determine the location of the shock sector with the use of substratal idiothesis only, because all putative intramaze cues were made irrelevant by angular displacements of the disk relative to the belt. Striking impairment of place avoidance by this "shuffling procedure" indicates that effective substratal idiothesis must be updated by exteroceptive intramaze cues.  (+info)

(8/278) CA1-specific N-methyl-D-aspartate receptor knockout mice are deficient in solving a nonspatial transverse patterning task.

In both humans and animals, the hippocampus is critical to memory across modalities of information (e.g., spatial and nonspatial memory) and plays a critical role in the organization and flexible expression of memories. Recent studies have advanced our understanding of cellular basis of hippocampal function, showing that N-methyl-d-aspartate (NMDA) receptors in area CA1 are required in both the spatial and nonspatial domains of learning. Here we examined whether CA1 NMDA receptors are specifically required for the acquisition and flexible expression of nonspatial memory. Mice lacking CA1 NMDA receptors were impaired in solving a transverse patterning problem that required the simultaneous acquisition of three overlapping odor discriminations, and their impairment was related to an abnormal strategy by which they failed to adequately sample and compare the critical odor stimuli. By contrast, they performed normally, and used normal stimulus sampling strategies, in the concurrent learning of three nonoverlapping concurrent odor discriminations. These results suggest that CA1 NMDA receptors play a crucial role in the encoding and flexible expression of stimulus relations in nonspatial memory.  (+info)