Behavioral significance of opioid peptides in relation to hippocampal function.
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5HT(2A/2C) and 5HT(3) receptors have an important role in cognitive behavior specially in spatial learning and memory but the literature concerning the role of these receptors in hippocampus in cognition remains controversial. In the present study a 5HT(2A/2C) antagonist ritanserin (0, 2, 4, 8 microg/0.5 microl) and a 5HT(3) antagonist granisetron (0.0, 0.05, 0.25, 0.5 microg/0.5 microl) were injected bilaterally into the CA1 region of rat hippocampus, 20 min before each training session in Morris Water Maze (MWM) task. Compare with control group, ritanserin (4 microg/0.5 microl) significantly reduced the escape latency and traveled distance of swimming to platform, but granisetron (0.25 microg/0.5 microl) significantly increased those parameters. Both drugs had no effect on escape latency and traveled distance of a non-spatial visual discrimination task. These results suggest a differential role of 5HT(2A/2C) and 5HT(3) receptors during spatial learning that ritanserin improves rat performance in spatial discrimination task whereas granisetron impairs it.
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The possible cerebral cortical circuitry for spatial memory in primates is discussed in light of a conceptual model and clinical as well as animal behavioral data. It is proposed that spatial memory formation begins with the arrival of sensory information in primary sensory areas and involves progressive elaboration through parasensory and higher-order association cortices. The connectivity between the association areas and the paralimbic and limbic regions is viewed as critical to the consolidation process. Finally, the execution of spatial behavior is presumed to involve the post-Rolandic and paralimbic projections to the frontal lobe. It is hoped that this conceptualization may provide a framework for further studies dealing with spatial memory.
A definitional system is given for the concepts of generality and specificity for behavioral variables, relating to signs and sizes of their intercorrelations. In particular, a mapping sentence is provided for defining the universe of observations for emotional behavior of mice under mild stress. Its three content facets are: (a) the temporal features of frequency, latency, and duration, (b) type of control, autonomic or voluntary, and (c) the experimental situation, the apparatus. Data from three studies published previously by other authors are analyzed by Smallest Space Analysis (SSA-I). In each case, the smallest space is found to be partitioned into contiguous regions corresponding to the elements of the three facets.
Current evidence indicates that repetitive motor behavior during motor learning paradigms can produce changes in representational organization in motor cortex. In a previous study, we trained adult squirrel monkeys on a repetitive motor task that required the retrieval of food pellets from a small-diameter well. It was found that training produced consistent task-related changes in movement representations in primary motor cortex (M1) in conjunction with the acquisition of a new motor skill. In the present study, we trained adult squirrel monkeys on a similar motor task that required pellet retrievals from a much larger diameter well. This large-well retrieval task was designed to produce repetitive use of a limited set of distal forelimb movements in the absence of motor skill acquisition. Motor activity levels, estimated by the total number of finger flexions performed during training, were matched between the two training groups. This experiment was intended to evaluate whether simple, repetitive motor activity alone is sufficient to produce representational plasticity in cortical motor maps. Detailed analysis of the motor behavior of the monkeys indicates that their retrieval behavior was highly successful and stereotypical throughout the training period, suggesting that no new motor skills were learned during the performance of the large-well retrieval task. Comparisons between pretraining and posttraining maps of M1 movement representations revealed no task-related changes in the cortical area devoted to individual distal forelimb movement representations. We conclude that repetitive motor activity alone does not produce functional reorganization of cortical maps. Instead, we propose that motor skill acquisition, or motor learning, is a prerequisite factor in driving representational plasticity in M1.
Following confinement to one chamber of a two-chamber exploration box (acquisition trial), male and female rats were intraperitoneally injected with saline, glucose (50, 100 mg/kg) or tacrine (1, 3 mg/kg). Twenty-four hours later they were given free access to this chamber and an identical novel one (retention trial). Tendencies to occupy the novel chamber (novelty-related location preferences) were increased by both doses of glucose for females and by the higher dose for males. While neither dose of tacrine affected this response for females, increased preferences occurred for males following the higher dose. However, when the higher doses of both agents were administered 2 h after acquisition, there were no significant effects for either sex. In view of the rats' lack of significant preferences for the novel chamber when treated with saline both immediately and 2 h after acquisition, the results were interpreted as sex-dependent attenuation of forgetting by post-acquisition treatment with both agents.
Male and female rats were assessed for effects of scopolamine on general activity, rearing and light-dark preferences when tested in either a familiar or a novel room. Males but not females reared more often when tested in the familiar rather than novel room, and the response was increased by scopolamine for all rats combined. Whereas scopolamine increased general activity for females (but not males) in the familiar room, it decreased the response for males (but not females) in the novel room. Females crossed more often between the dark and light sides of a light-dark box and, when treated with saline but not drug, spent more time in the light side than males. Scopolamine reduced the amount of time spent in the light side for females only. While the results were discussed mainly in terms of sex differences in fearfulness, their principal value was in demonstrating the effectiveness of room novelty and sex in determining levels of the behaviors recorded, and drug responsiveness.
A recent study (Tommasi & Thinus-Blanc, 2004) found that when rats trained to search for food hidden in the center of a square-shaped enclosure were tested in the absence of food, they searched precisely in the center of the enclosure. Transfer tests carried out in enclosures differing in shape or size (rectangular-, large square-, and equilateral triangle-shaped) showed that rats searched in the geometric center of the novel environments. In the present work, half of those rats were lesioned bilaterally to the hippocampus and were then re-trained and re-tested in the same task, to be compared to sham rats that received the same retraining/re-test protocol. Results show that lesioned rats, although unimpaired in relearning to localize the center of the square-shaped enclosure, performed considerably worse than sham rats in the transfer tests in the enclosures differing in shape, suggesting a relevant role of the hippocampus in geometry-driven place generalization.
The abuse of androgens may be related to their ability to produce positive, hedonic interoceptive effects. Conditioned Place Preference (CPP) has been used in many experiments to examine hedonic effects of drugs. This review is focused on studies from our laboratory that utilized CPP to examine potential positive hedonic effects of testosterone (T), and its androgenic metabolite dihydrotestosterone (DHT), and its metabolite 3alpha-androstanediol (3alpha-diol). We hypothesized that administration of a high concentration of 3alpha-diol would produce a CPP, pharmacological concentrations of plasma androgens, and alter androgen receptors (AR) and the function of GABA(A)/benzodiazepine receptor complexes (GBR). In our studies, we observed that systemic 3alpha-diol (1.0 mg/kg) prior to exposure to the non-preferred side of a CPP chamber significantly increased preference for the non-preferred side of the chamber compared to baseline preference and homecage controls. Furthermore, administration of T, DHT, or 3alpha-diol increased levels of these androgens, decreased ARs (decreased seminal vesicle weight and intrahypothalamic AR) and GBR function (decreased GABA-stimulated chloride influx in cortical synaptoneurosomes, and muscimol binding in the hippocampus compared to control groups). With systemic administration of 3alpha-diol that enhanced CPP, concentrations of 3alpha-diol were increased in the nucleus accumbens (NA). Central implants of T, DHT, or 3alpha-diol to the NA also produced a CPP compared to baseline preference and vehicle controls. These data indicate that systemic 3alpha-diol is more effective at enhancing CPP and increasing circulating 3alpha-diol levels than is T or DHT and that central administration of 3alpha-diol to the NA can condition a place preference. These findings indicate that 3alpha-diol produces positive hedonic effects and suggest that T's variable effects on CPP may be due in part to T's metabolism to 3alpha-diol.
Infant rats (Rattus norvegicus) placed on a shallow incline (2 degrees, 4 degrees, or 8 degrees) oriented and moved downhill within 1 min; that is, they displayed positive geotaxis. Their downhill translocation increased with angle of inclination. A variety of possible behavioral elements (e.g., initial orientation, rotational movements, ambulatory velocities) were eliminated as explanations of the geotaxis. Wall contact was recognized as a determinative event: Pups on the inclines showed no orientation with respect to the geogravitational stimulus before contacting a wall. The event of wall contact, however, evoked reliable downhill orientation and more linear movements. Positive geotaxis was created by pups' orientation against walls and an associated increase in movement velocity. This is a distinct perspective on a behavioral response that replaces a traditionally misinterpreted phenomenon. The authors discuss the ecological validity and historical context of these findings.
Domestic dogs (Canis familiaris) perform above chance on invisible displacement tasks despite showing few other signs of possessing the necessary representational abilities. Four experiments investigated how dogs find an object that has been hidden in 1 of 3 opaque boxes. Dogs passed the task under a variety of control conditions, but only if the device used to displace the object ended up adjacent to the target box after the displacement. These results suggest that the search behavior of dogs was guided by simple associative rules rather than mental representation of the object's past trajectory. In contrast, Experiment 5 found that on the same task, 18- and 24-month-old children showed no disparity between trials in which the displacement device was adjacent or nonadjacent to the target box.
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Poecilogony is the production of more than one type of young within a single species of marine invertebrate. We chose a poecilogonous polychaete to investigate potential differences in morphogenesis among offspring that are polymorphic in dispersal potentials (planktonic, benthic) and trophic modes (planktotrophy, adelphophagy). Differences in morphogenesis occur and are strongly influenced by maternal type. Females that provide extra-embryonic nutrition (as nurse eggs; type III females) also produce offspring with an accelerated onset of juvenile traits, relative to planktotrophic offspring of females that do not provide extra-embryonic nutrition (type I females). Thus, progeny of some females appear morphologically preadapted for a benthic lifestyle. Surprisingly, differences in phenotype among offspring do not parallel offspring ecotype, as offspring with early onset of juvenile traits (III) are ecologically bimodal. Some Type III offspring eat the nurse eggs (adelphophagy), have accelerated development, and hatch as benthic juveniles. In contrast, their siblings hatch as small, planktotrophic, dispersive larvae that are morphologically similar to their type III siblings, but ecologically similar to Type I planktotrophic larvae. We propose that poecilogony evolved through sequence heterochrony in morphogenesis with accelerated onset of juvenile traits in type III offspring. In addition, we suggest that heterochrony in life-history events (hatching, metamorphosis) also occurs, thereby generating offspring that are dimorphic in both phenotype and ecotype. Over time, selection acting on different levels of ontogeny (morphogenesis vs. dispersal) may balance this polymorphism and allow poecilogony to persist.
Insects of several species rely on visual landmarks for returning to important locations in their environment. The "average landmark vector model" is a parsimonious model which reproduces some aspects of the visual homing behavior of bees and ants. To gain insights in the structure and complexity of the neural apparatus that might underly the navigational capabilities of these animals, the average landmark vector model was implemented in analog hardware and used to control a mobile robot. The experiments demonstrate that the apparently complex task of visual homing might be realized by simple and mostly peripheral neural circuits in insect brains.
We examined, with event-related fMRI, two hypotheses about the organization of human working memory function in frontal cortex: (1) that a region immediately anterior to the frontal eye fields (FEF) (superior frontal cortex, SFC) is specialized for spatial working memory (Courtney, et al., 1998); and (2) that dorsolateral prefrontal cortex (PFC) plays a privileged role in the manipulation of spatial stimuli held in working memory (Owen, et al., 1996; Petrides 1994). Our delayed-response task featured 2-D arrays of irregularly arranged squares that were highlighted serially in a random sequence. The Forward Memory condition required maintenance of the spatio-temporal sequence, the Manipulate Memory condition required reordering this sequence into a new spatially defined order, the Guided Saccade condition required saccades to highlighted squares in the array, but no memory, and the Free Saccade condition required self-paced, horizontal saccades. The comparison of fMRI signal intensity associated with 2-D saccade generation (Guided Saccades) versus fMRI signal intensity associated with the delay period of the working memorials condition revealed no evidence for greater working memory-related activity than saccade-related activity in SFC in any individual subject, nor at the level of the group, and greater 2-D saccade than delay-period activity in three of five subjects. These results fail to support the hypothesis that spatial working memory-related activity is represented preferentially in a region of SFC anterior to the FEF (Courtney, et al., 1998). The comparison of maintenance versus manipulation of spatio-temporal information in working memory revealed significantly greater activity associated with the latter in dorsolateral PFC, but not in ventrolateral PFC or in SFC. These results suggest that the delay-related function of SFC is limited to the maintenance of spatial information, and that this region does not support the nonmnemonic executive control functions supported by dorsolateral PFC. These results also indicate that the preferential recruitment of dorsolateral PFC for the manipulation of information held in working memory applies to tasks employing spatial stimuli, as well as to tasks employing verbal stimuli (D'Esposito, et al., 1999); Petrides et al., 1993; Postle et al., 1999).