Strain distribution of mice in discriminated Y-maze avoidance learning: genetic and procedural differences

The current study was conducted to characterize discriminated avoidance learning in mice by using a Y-maze task. In Experiment 1, the task parameters were manipulated, including the amount of time spent in the start arm, the amount of time to make the avoidance response, and the intertrial interval (ITI) using C57 x SJL F1 hybrid mice. Avoidance performance was significantly improved with longer times to avoid the shock and longer ITIs. In Experiment 2, mice from 4 inbred strains (BALB/cByJ, DBA/2J, C57BL/6J, and SJL/J), an F1 hybrid (C57 x SJL), and 1 outbred strain (CD1) were tested with various ITIs. Strain differences were observed in avoidance learning, with BALB, DBA, C57 x SJL and CD1 mice showing significantly better avoidance learning than C57 mice, which were better than SJL mice. These data demonstrate that Y-maze performance is significantly influenced by the genetic background of the mouse and the parameters of the task.     

A comparison of shock avoidance learning in headless cockroaches in leg-lifting and lowering task

Headless cockroaches were trained either to lift or to lower the prothoracic leg to avoid electric shocks. The learning process in both cases was very distinct. However, the learning performance in the lifting was better than in the lowering task. The reason for this poorer learning in the lowering task is due to the unconditioned leg raising movement of the animals to electric shocks. This unconditioned response affects the headless cockroaches avoid shocks in the lifting task by escape learning, whereas they avoid shocks in the lowering task by true avoidance learning. Injection of 30 microliter of Ringer's solution has no significant effect on the learning process in the lifting task. In the lowering task, however, Ringer's solution impairs the learning ability considerably. Crude extract of corpora cardiaca strongly inhibits the learning of both tasks.     

Passive avoidance response in mice infected with Schistosoma mansoni

Schistosomiasis is a parasitic disease of humans and rodents affecting more than 200 million people worldwide. Following the onset of infection, the worms induce granulomas around schistosome eggs in the liver, intestine and central nervous system (both brain and spinal cord), which are likely to cause changes in cognitive functions. In the present study, CD-1 female mice were percutaneously infected with 60 cercariae of Schistosoma mansoni and the effect on the mice's cognitive abilities were assessed by using the passive avoidance learning paradigm both in an early and a late phase of infection (independent groups). The results of the study show that infected animals without brain granulomas (early phase) had impairments in their passive avoidance response, whereas mice with brain granulomas (late phase) behaved as uninfected ones. Moreover, a decreased propensity to start exploration was observed in mice with granulomas in the brain. The results suggest that the murine model of infection may be a useful tool for studying human neuroschistosomiasis.     

Blockade of bombesin-like peptide receptors impairs inhibitory avoidance learning in mice

Several studies reported that peripheral administration of bombesin (BN) and gastrin-releasing peptide (GRP) improved some forms of memory performance. In the present study, we examined the role of endogenous BN-like peptide(s) for the acquisition of inhibitory avoidance learning in mice using BN-like peptide receptor antagonists. An administration of [Leu(13)-(psi-CH(2)NH)-Leu(14)]BN (antagonizes GRP-R>neuromedin B receptor (NMB-R)) impaired the performance of inhibitory avoidance learning in all doses (16, 32, 64 nmol/kg). While the effect was somewhat lesser than [Leu(13)-(psi-CH(2)NH)-Leu(14)]BN, BIM23127 (antagonizes NMB-R>GRP-R) also impaired performance in a moderate dose (32 nmol/kg). These results showed that endogenous BN-like peptides have some role(s) for the modulation of learning and memory, and suggest that NMB/NMB-R pathway may also be involved in the memory acquisition and modulation as well as GRP/GRP-R pathway.     

Competition between an avoidance response and a safety signal: Evidence for a single learning system

Two experiments examined competition between an instrumental avoidance response and a Pavlovian safety signal for association with omission of electric shock in a human fear conditioning paradigm. Self-reported shock expectancies and skin conductance responses were consistent with blocking of learning of the instrumental contingency by prior training of the Pavlovian contingency, and vice versa. The results support the idea that a common learning mechanism underlies both Pavlovian and instrumental conditioning. The expectancy data suggest that this learning mechanism is cognitive in nature, and that Pavlovian and instrumental learning involve external and internal attributions, respectively. The procedure may thus serve as a laboratory model for attributional processes involved in the acquisition of threat expectancies in anxiety and anxiety disorders.     

Heart rate response to shock delivered via different implanted electrodes

The heart rate reaction elicited by electric shock was studied in rats stimulated via implanted electrodes that were placed entirely beneath the skin (subcutaneous electrodes) or were passed under and through the skin (cutaneous electrodes). Cutaneous shock elicited greater cardioaccelerations than subcutaneous shock except at very low intensities. This finding may help to explain differences in conditioned heart rate responses when these two types of electrodes are used to deliver shock stimuli.     

Phenotypic and genetic correlations between evoked EEG/ERP measures during the response anticipation period of a delayed response task

We investigated the relationship between three electrophysiological indices of response anticipation in a spatial delayed response task with a low and high memory load manipulation: a slow cortical potential (SCP), theta desynchronization, and upper alpha synchronization. Individual differences in these three measures were examined in 531 adult twins and siblings. Heritability of the SCP at occipital-parietal leads varied from 30% to 43%. Heritability of upper alpha synchronization (35% to 65%) and theta desynchronization (31% to 50%) was significant at all leads. Theta desynchronization and upper alpha synchronization were significantly correlated ( r ∼43%), but SCP was not correlated with either. The effect of working memory load on all three measures was not heritable. Response anticipation reliably evokes an SCP, upper alpha synchronization and theta desynchronization, but variation in these measures reflects different (genetic) sources.     

Differences in one-way active avoidance learning in mice of three inbred strains

DBA/2J, C57BL/6J, and C3H/HeJ mice were given 10 one-way avoidance training trials per day, using an unconditioned stimulus intensity that provided equivalent motivation for learning to mice of all three strains, and were found to differ in their abilities to learn and retain the response. DBA/2J mice acquired the response in fewer days than did the mice of the other two strains, although C57BL/6J mice eventually reached a level of performance similar to that of DBA/2J mice. Both the rate of acquisition and the level at which avoidance performance stabilized were significantly lower in C3H/HeJ, than in DBA/2J or C57BL/6J, mice. In addition, DBA/2J mice showed a significantly greater task retention from one testing day to the next than did C57BL/6J or C3H/HeJ mice.This work was supported by National Institute on Drug Abuse Grants DA04195 and DA06192 to J.L.M. and Mental Health Grant MH-47680 to G.F.K.     

Passive avoidance learning in hippocampectomized rats under different shock and intertrial interval conditions.

Two experiments were run comparing the performance of normal, cortically damaged and hippocampally damaged rats on a passive avoidance task [37]. The results of Experiment 1 indicated that hippocampally damaged rats learn to passively avoid after no more than three consecutive punishment trials. In Experiment 2, the passive avoidance performance of groups of normal, cortically damaged, or hippocampally damaged rats was studied using a factorial combination of two intertrial intervals (60 sec and 60 min) and two shock intensities (1.8 mA and 1.8 mA). Results indicated that the greatest and most persistent deficits in the performance of hippocampally ablated animals occurred in the low shock, short intertrial interval condition. No differences between the performance of hippocampally damaged animals and control animals were found in the high shock, long intertrial interval condition. Performance of the hippocampectomized animals in the remaining groups was poorer than controls, but intermediate between the performance of the hippocampal animals in the aforementioned groups. Results were interpreted as supporting an information processing model of hippocampal function.     

Cardiac changes to signalled shock avoidance in dogs

Alterations in heart rate (HR), left ventricular pressure (LVP), and maximum left ventricular dp/dt (LVdp/dt max) during a signalled avoidance task were studied in eight chronically prepared dogs. Four of these animals comprised a non-shock control group. In experimental animals, HR increased during the first two days of the avoidance task but did not change significantly during the last two days, while LVP remained at the supranormal post-training levels and LVdp/dt max increased over the course of the experiment. Control animals showed no change in HR or LVP, but LVdp/dt max decreased over the four experimental days. Changes in LVdp/dt max in experimentals reflect a consistent increase in cardiac sympathetic activation. However, HR changes indicate an initial increase and a subsequent decrease in sympathetic activity. It was therefore postulated that either differential activation of sympathetic cardiac fibers occurred such that during non-stress periods and subsequent exposure to stress, sympathetic influences predominate which are reflected only in LVdp/dt max changes, or sympathetic and parasympathetic fibers differentially control cardiac function during stress and non-stress conditions.     

A simple and versatile avoidance chamber for mice requiring no shock scrambler

We present a simple two-chamber apparatus for avoidance training of mice which does not require a shock scrambler. This apparatus can be used for active, passive and discriminated (Go-No-GO) avoidance tasks.     

Stress-induced impairment of inhibitory avoidance learning in female neuromedin B receptor-deficient mice

Neuromedin B (NMB) is a mammalian bombesin (BN)-like peptide that exerts its function via the neuromedin B receptor (NMB-R). The NMB/NMB-R system is involved in stress response, and therefore we examined behavioral properties in female mice lacking NMB-R using a restraint-induced stress paradigm. Thirty minutes of restraint in a wire mesh cage constituted a sufficient stress stimulus for mice as evidenced by elevated blood glucose concentrations in stressed wild-type and NMB-R-deficient mice. Using a one-trial passive avoidance test, stressed NMB-R-deficient mice exhibited a marked reduction in memory performance. NMB-R-deficient mice exhibited elevated spontaneous activity in a novel environment compared to non-stressed mutant mice after 30-min stress, and a similar difference was also observed between stressed/non-stressed wild-type mice. An elevated plus maze test showed that the stress stimulus had no effect on anxiety in either wild-type or NMB-R-deficient mice. Furthermore, pain response of wild-type and NMB-R-deficient mice induced by electric foot shock was not affected under either stressed or non-stressed conditions. These results indicate that impaired memory performance in stressed NMB-R-deficient mice is not a consequence of changes in spontaneous activity, anxiety, or pain response, and suggest that the NMB/NMB-R pathway may play a role in regulating the stress response via the neural system that controls learning and memory.     

A quantitative genetic analysis of runway learning in mice

Summary Individual differences in the acquisition and extinction of a straight runway response were studied. Sixty-four pairs of mice chosen from a heterogeneous population and motivated by hunger were given 5 massed trials a day in the runway for 5 days of acquisition and 3 days of extinction. They were then mated at random and their offspring were tested using the same procedures. A second degree polynomial function (Y = a - bX - + -²) was fitted to the learning curve of each individual. Since learning may be defined as change in behavior, a, b and c may be regarded as overall activity, amount of learning and rate of learning respectively. Estimates of the heritability were made by regressing the means of the offspring on the parent means. Heritability estimates of the 3 parameters of the learning curve (the mean, b and c) were respectively 0.41±0.12, 0.30±0.10, and 0.26±0.14 for running times and 0.36±0.11, 0.19±0.12, and 0.25±0.10 for starting times. The correlations between traits were also partitioned into their genetic and environmental components. This analysis suggested that many of the same genes were contributing to individual differences in the comparable components for running and starting times for acquisition and extinction.From a thesis submitted by the senior author in partial fulfillment of the requirements for the Ph.D. degree at the University of Colorado. This research was supported by research grant GM-14547 from the National Institute of General Medical Sciences.     

Impaired passive avoidance learning in mice lacking central neuronal nicotinic acetylcholine receptors

The nicotinic cholinergic system influences cognition, anxiety, locomotion, and addiction by acting upon nicotinic acetylcholine receptors (nAChRs). To date, there are 12 known neuronal mammalian nAChR subunits leading to a rich pharmacological diversity that is difficult to attribute to specific subunits. We generated alpha7-beta2 nAChR double mutant mice by breeding to investigate the effect of a minimal number of nAChRs in the CNS. These mice have been used to determine the role these receptor subunits play in a variety of behaviors. A battery of behavioral tests was used to determine the effect of the mutation in anxiety, locomotor activity, startle response, pre-pulse inhibition, motor coordination and learning and memory. Mice lacking both the alpha7 and the beta2 nAChR subunits displayed impaired learning and memory performance in a passive avoidance test and showed enhanced motor performance on the rotarod.     

Implicating causal relations between cellular function and learning behavior

Learning in the nudibranch mollusc Hermissenda shows many features of vertebrate associative conditioning. Pairings of light and rotation produce conditioned suppression of phototaxis, which is retained for days, shows savings, extinction, contingency sensitivity, and, recently, temporal specificity. In addition, specific features of the behavior have been shown to undergo classical Pavlovian conditioning. Extensive analysis of the neural networks mediating the flow of visual and graviceptive information have demonstrated convergent pathways at specific cellular loci. These cells are critically implicated for a primary role in the conditioned modifications of behavior. A variety of experimental approaches consistently support the proposal that reductions of specific K+ currents in the Type B photoreceptor soma play a causal role for several different behavioral expressions of the conditioning. In this article, we review several of these behaviors to show how the demonstrated close temporal correspondence of cellular and behavioral functions further implicates certain causal relations. For example, studies of the shadow withdrawal behavior of Hermissenda suggest a causal relation between the long-lasting depolarization of the Type B photoreceptor and the animal's reduced ability to turn towards the light at light/dark boundaries. Whereas the shadow response corresponded to cellular events at the end of a light step, responses to the onset of light or rotation were largely unexplored. By using a different approach, we identified behavioral responses during the first few seconds of stimulation with light and rotation. These responses, for which Pavlovian conditioning was demonstrated, correspond closely in time to known cellular correlates.(ABSTRACT TRUNCATED AT 250 WORDS)