Start Box Research Articles

Locomotor behaviour in dairy calves, the use of demand functions to assess the effect of deprivation

The aim of the present study was to examine if pause in testing is a confounding factor when demand functions are used to assess the effect of length of deprivation of locomotion on the motivation to perform locomotor behaviour in dairy calves. It was investigated if calves’ ability to respond operantly for access to perform locomotor behaviour in an exercise arena declined when there was a long pause in operant testing (4 days) compared to a short pause in operant testing (1 day). Six calves were used and within operant sessions they worked on one of three fixed ratios (FR 8, 16 or 24). The motivation to perform locomotor behaviour was controlled by giving free access to the exercise arena between operant sessions when there were long pauses between these. A pause of 1 or 4 days in operant testing affected neither the demand function based on the number of rewards per session (common demand function: y=3.5−0.82 x), nor the demand function based on the overall time calves spent galloping/bucking during the rewards (common demand function: y=4.2−0.26 x). Furthermore, the length of pause in operant testing did not affect the median latency to press the panel after entering the start box (36 s) or the median interval between a successive number of times pressing the panel (1.8 s). Thus, no adverse effects of a 4 day pause in operant testing compared to a 1 day pause were found on the calves ability to respond during operant sessions.

Hyperdopaminergic Mutant Mice Have Higher “Wanting” But Not “Liking” for Sweet Rewards

What is the role of dopamine in natural rewards? A genetic mutant approach was taken to examine the consequences of elevated synaptic dopamine on (1) spontaneous food and water intake, (2) incentive motivation and learning to obtain a palatable sweet reward in a runway task, and (3) affective "liking" reactions elicited by the taste of sucrose. A dopamine transporter (DAT) knockdown mutation that preserves only 10% of normal DAT, and therefore causes mutant mice to have 70% elevated levels of synaptic dopamine, was used to identify dopamine effects on food intake and reward. We found that hyperdopaminergic DAT knockdown mutant mice have higher food and water intake. In a runway task, they demonstrated enhanced acquisition and greater incentive performance for a sweet reward. Hyperdopaminergic mutant mice leave the start box more quickly than wild-type mice, require fewer trials to learn, pause less often in the runway, resist distractions better, and proceed more directly to the goal. Those observations suggest that hyperdopaminergic mutant mice attribute greater incentive salience ("wanting") to a sweet reward in the runway test. But sucrose taste fails to elicit higher orofacial "liking" reactions from mutant mice in an affective taste reactivity test. These results indicate that chronically elevated extracellular dopamine facilitates "wanting" and learning of an incentive motivation task for a sweet reward, but elevated dopamine does not increase "liking" reactions to the hedonic impact of sweet tastes.

Instrumental conditioning of choice behavior in male Siamese fighting fish (Betta splendens).

Despite the differences in the response of male Betta splendens toward various stimuli, no research has attempted to determine the preference for a live conspecific versus a mirror presentation. A submerged T-maze was used to present both stimuli to healthy male B. splendens (N=16). The results indicated that subjects' start box and swimway latencies decreased significantly over the 30 trials. Moreover, the analysis of choices demonstrated a modest, but statistically significant, preference for the live conspecific over the mirror presentation. The results are discussed in terms of the stimuli qualities that elicit an aggressive response in B. splendens and the implications for common experimental procedures.

Early T-maze behavior and broiler growth

In the laboratory and at a commercial farm in Argentina, chicks that showed a short latency to exit a T-maze (LEX) (HP, high performance) gained more weight than those with a longer LEX (LP, low performance). The present study re-examined this relationship and evaluated additional T-maze measures using broilers reared in quasi-intensive, environmentally controlled conditions. In the T-maze, a mirror strategically placed at the end of a corridor stimulates the test chick to leave the isolation chamber (start box) and to move toward its reflection. Having done so, it can then see other birds and thereby be further stimulated to completely exit the maze. However, when a test bird hesitates or stops at the mirror, its performance categorization may be confounded. Herein, the T-maze performance of 3-d-old broiler chicks was assessed using three different measurements: 1) the latency to exit the start box (LEB), 2) the latency to reach the mirror section of the maze (LRM), and 3) LEX. The fastest (top 25%) and slowest (bottom 25%) of the birds within a sex and within each of the three T-maze criteria were classified as HP and LP chicks, respectively. The relationships between these measures and body weight were examined in 4-, 42-, and 56-d-old males and females. Irrespective of the T-maze classification criteria used, HP and LP chicks had similar body weights at 4 d of age. However, chicks classified as HP according to LEB or LRM measures were heavier at 42 and 56 d of age than LP ones (P < 0.02 for all comparisons). These differences were apparent in both sexes. On the other hand, there were no detectable differences in body weight at the latter ages between chicks categorized as HP or LP according to their LEX scores. The present results indicate that 1) broiler chicks that exit the T-maze start box and reach the mirror quickly subsequently grow faster than their slower LP counterparts and 2) LEB and LRM are better predictors of growth than the LEX value used in previous studies.

Neonatal social isolation alters both maternal and pup behaviors in rats.

The development of emotional behavior is dependent on the early experiences of the infant and the quality of maternal care. In these experiments, the effects of social isolation during the preweaning period on both pup behavior and maternal responsivity were examined. In the first study, the number of ultrasonic vocalizations (USVs) emitted after brief maternal separation was measured in neonatal rats with differing histories of social isolation. The social isolation procedure consisted of 5 days of daily separation from the dam and littermates for either 3 or 6 hr. At both ages tested, socially isolated pups vocalized significantly less than control pups. In the second study, the effects of prior isolation either daily for 5 previous days (Chronic Isolation) or for 4 hr prior to testing (Acute Isolation) were examined in a T-maze choice test. Pup vocalizations in the presence of the dam and dams' maternal behavior were assessed. When the dam was confined to the start box or during the maternal free access period, both Chronic and Acute Isolates vocalized less than pups that had never left the home nest. Dams spent more time with and licked and groomed more frequently and for a longer time both Chronic and Acute Isolates compared to pups that had always been with dams in the home nest. These results suggest that early isolation experience can alter subsequent responses to separation stress in neonatal rats and that maternal behavior is sensitive to the prior experiences of offspring.

Residential maze as a task for testing rats' maze learning ability: effects of hippocampal lesions and cholinergic receptor antagonists.

We investigated whether rats can learn mazes by a procedure in which rats were left in the maze (residential maze) in groups for 1 h a day. Water and food locations, which served as the start and goal boxes respectively in the test trial, were at the opposite ends of the maze. On the test trial conducted everyday before the residence period, animals put in the start box showed a significant decrease of the error response into the blind alleys and running time to reach the goal box. Systemic administration of scopolamine (0.25, 0.5 mg/kg), a muscarinic receptor antagonist, dose-dependently increased the number of errors, but mecamylamine, a nicotinic receptor antagonist, had no effect. Bilateral hippocampal lesions retarded both the acquisition and retention of this maze learning. The results suggest that this residential maze procedure is useful for testing maze learning ability in rats.

Sex and type of feed effects on motivation and ability to walk for a food reward in fast growing broilers

Housing conditions, body weight, leg problems and pain influence behaviour of broilers. Apart from the physical ability, little is known about the motivation to perform behaviour. The distinction between motivation and ability is relevant as a lack of motivation has consequences for the interpretation of, e.g. the observed immobility in terms of compromised welfare. A runway experiment with fast growing broilers was conducted to investigate the influence of sex and type of feed on motivation and ability to walk for a food reward (mealworm) without depriving the birds from feed before testing. Twenty-four males and 24 females fed with two types of feed, conventional or free-range (less energy and protein) feed, were individually tested in a 2 m long runway from four to seven weeks of age. Five bowls were placed in the runway, one at every 40 cm. Three sessions were applied within 1 week (1) control session: each bowl contained one mealworm; (2) frustration session: the first four bowls were empty, the last bowl contained five mealworms, and (3) obstacle session: each bowl contained one mealworm and 10 cm high obstacles were placed between the bowls. Weekly, body weight and feed consumption were measured and gait score was assessed of each individual. Over all weeks, birds walked faster in frustration sessions than in control or obstacle sessions and faster in control than in obstacle sessions. Birds sat more in obstacle than in control sessions, indicating that ability to walk was affected by the difficulty of the task. Males walked faster in control and obstacle sessions than females, despite the higher body weight. The number of vocalisations in the runway decreased over time and males vocalised more than females. In both sexes, free-range fed birds vocalised more than conventionally fed birds. Differences between frustration and control sessions and obstacles and control sessions at individual level within a week were also measured, called the motivation and the ability effect. Concluded is that sex and type of feed have effects on different measures in the runway. Male broilers walked faster to a food reward and vocalised more than females. The role of type of feed was ambiguous. It did not influence body weight, walking speed or gait score, but conventionally fed birds sat more and had a higher latency to leave the start box and to reach the last bowl, and free-range fed birds vocalised more. No sex or feed differences were found for the motivation and the ability effect. That means that frustration and obstacles had similar impact on both sexes and both types of feed and that sex differences in walking speed probably were a result of physical differences (males are stronger and bigger).

Individual recognition after fighting by golden hamsters: A new method

Individual recognition is crucial for many aspects of social behavior and may be a specially evolved type of learning and memory. Using golden hamsters, we developed a behavioral method for the investigation of individual recognition. After a series of three brief fights, the two males were categorized as winners or losers. In Experiments 1 and 2, the loser was then tested in a Y-maze after four different intervals (30 min, 1 day, 3 days and 7 days). In Experiment 1, the familiar winner was confined in a stimulus compartment at the end of one arm of the Y, whereas no animal occupied the opposite arm. The results showed that the losers in the experimental group spent the most time in the base of the Y (in or near the start box). They also showed hesitancy to approach the winners' odors and spent less time near them than they spent in the same area when tested with no stimulus males present. In contrast, No Fight control males spent the most time near the stimulus males and did not hesitate in approaching them. In Experiment 2, losers spent less time near the odors of a familiar winner than control losers spent near unfamiliar winners, suggesting recognition of a particular winner. In Experiment 3, the losers were tested just once, 7 days after the last interaction. Again, they spent the most time in the base of the Y and avoided the arm with odors of their specific winners. These results suggest that losers learn to recognize individuals during brief interactions and remember this information for both the short term (30 min) and the long term (at least 1 week). This behavioral method will be useful for further investigation of individual recognition and the neural mechanisms underlying this kind of memory.

Effects of Early Contact with Maternal Parent on Locomotor Activity and Exploratory Behavior in Spiderlings of Hogna carolinensis (Araneae: Lycosidae)

In this study we investigated the effect of rearing conditions (stimulus complexity) on the locomotor activity and exploratory behavior of spiderlings of Hogna carolinensis in a novel open field arena. Experimental groups consisted of spiderlings that were allowed to remain with their maternal parent for 1 day (group 1), 3 days (group 2), and 5 days (group 3) after emergence from their egg sacs, and those who had no contact (group 4) with a maternal parent. Spiderlings that had physical contact with their mothers for 3 and 5 days required significantly less time to enter the arena, to reach the central grid area of the arena, and for an initial return to the start box than spiderlings in groups 1 and 4. In addition, spiderlings in groups 2 and 3 exhibited a significantly greater number of grid crossings as compared to groups 1 and 4, and spent more time in the arena. This is the first demonstration that environmental complexity, in the form of a social factor such as physical contact with a maternal parent, can affect the subsequent behavior of spiderlings.

The emergence test: effects of psychotropic drugs on neophobic disposition in Wistar Kyoto (WKY) and Sprague Dawley Rats

1. The Emergence Test (ET), a variation of the open field test in which the rat is not handled, and is purported to measure neophobia, was applied to Wistar Kyoto (WKY) and Sprague Dawley (S-D) rats. 2. While no-stress control WKY rats were less active in the ET, pre-treatment with shock stress exacerbated strain differences. WKY rats, previously exposed to shock, did not emerge from the home cage start box during repeated testing, whereas previously stressed S-D rats vacated the home cage quickly and revealed increasing behavioral agitation. 3. Diazepam reduced emergence latency only in S-D rats, whereas nomifensine significantly increased head poke responses in WKY rats. 4. WKY rats responded to the ET with characteristically depressive behavior, whereas S-D rats responded to the same ET with behavioral agitation and anxiety. The implications of these behavior patterns for discriminating between anxiety and depressive behavior are presented.

Abstracts for the IXth World Congress of Psychiatric Genetics, Saint Louis, Missouri

The Puzzle Box is a new intelligence task for mice, which has been developed as part of our ongoing research in the characterisation of general cognitive ability (g) in mice. Puzzle tasks used to assess g in rats were adapted and extended to complement spatial and exploratory tasks in our battery. The apparatus is a box 73×29 cm, divided by a removable barrier into a small dark goal box and a larger brightly lit start box. Mice are presented with a series of puzzles to solve in order to enter the goal box. These include filling an underpass with sawdust, where the mouse has to burrow through, blocking the entrance with a cardboard plug which the mouse must pull out, or presenting a set of mouse-size 'cat-flap' doors. Individual differences analyses on our heterogeneous stock (HS) mice show that these mice can solve the problems with certain mice consistently outperforming others. Comparisons with other well-known cognitive tests also show that these tasks are good measures of g. Further analyses have identified difficulty levels, consistency and g-loadings of the task items. Task design has been refined on this basis to allow quicker and easier testing with tasks proven to be reliable. The Puzzle Box is therefore recommended as a useful addition to a cognitive battery in mice.

Anxiogenic-Like Effects Limit Rewarding Effects of Cocaine in BALB/cByJ Mice

Previous studies have reported intravenous cocaine self-administration behavior in several strains of mice with the exception of BALB/cByJ, a strain considered a mouse model of high emotional reactivity. The present experiments further investigated acquisition of self-administration in BALB/cByJ mice using a low dose and a habituation session. Following evidence of an initial drug-seeking behavior, we observed a progressive decline of intravenous self-administration. Pretreatment with diazepam (0.5 mg/kg, IP), reinstated cocaine-maintained responding. To test the hypothesis that injections directly into a reward-relevant brain region might support consistent cocaine-seeking behavior, BALB/cByJ mice implanted in the nucleus accumbens (NAc) or the caudate-putamen nucleus (CPu) were trained to discriminate between the arm enabling a microinjection of cocaine (30 pmol/50 nl or 150 pmol/50 nl) and the neutral arm of a Y-maze. Only NAc subjects exhibited a spatial discrimination toward the cocaine-reinforced arm and the D2 antagonist, sulpiride (50 mg/kg, IP) eliminated intra-NAc cocaine self-administration. However, after several days of cocaine self-injection, animals developed an approach/avoidance-like behavior between the start box and the reinforced arm. This behavior was suppressed by systemic diazepam (1 mg/kg, IP) pretreatment. We conclude that: (1) medio-ventral NAc is involved both in the rewarding (via a D2 dopaminergic mechanism) and aversive effects of cocaine in mice; and (2) anxiolytic pretreatment (diazepam) indirectly enhanced the reinforcing properties of cocaine in BALB/cByJ, suggesting that emotionality can act as a protective mechanism against stimulant abuse.

Effects of an acute stressor on fear and on the social reinstatement responses of domestic chicks to cagemates and strangers

Genetic selection for appropriate levels of sociality (motivation to be with conspecifics) could benefit poultry welfare and performance. Runway tests that require chicks to traverse a corridor in order to reach other chicks in a goal box are commonly used to measure this behavioural trait. However, we need to determine if the chicks’ responses in such tests are sensitive to certain experiential variables before we can recommend possible selection criteria for future breeding programmes. The present study focused on fear and on the identity of the stimulus birds. Broiler chicks either remained undisturbed or were exposed to an acute stressor (mechanical restraint) before their tonic immobility fear responses were measured 1 h later in Experiment 1. Exposure to the stressor significantly prolonged tonic immobility and, hence, presumably, underlying fear levels. In Experiment 2, the responses of stressed chicks and undisturbed controls were assessed when they were tested individually in a runway with a goal box containing either familiar or unfamiliar chicks of the same age. Our finding that stressed chicks emerged from the start box sooner and spent longer near the stimulus birds suggests that exposure to a frightening event increased social reinstatement motivation. Furthermore, social affiliation was more pronounced when the goal box contained familiar cagemates rather than strange chicks, regardless of prior treatment. This finding demonstrates that broiler chicks that were housed in groups of twelve can discriminate between familiar and unfamiliar conspecifics encountered in novel surroundings. Thus, sociality was positively associated with fearfulness and broilers clearly showed social discrimination in runway tests. These findings highlight the dangers of disregarding variables, such as fear and the capacity for social recognition in tests of social motivation. We strongly recommend that exposure to frightening events prior to test should be avoided and that the identity of the birds in the runway goal box should be standardized, i.e. either familiar or unfamiliar, and noted.

BEHAVIOUR OF DOMESTIC PIGS IN A VISUAL PERSPECTIVE TAKING TASK

Abstract Animals with visual perspective taking abilities should differ in their responses to individuals that do and individuals that do not have visual access to some critical event. We investigated whether domestic pigs show behaviour consistent with this ability. Ten subjects were trained to move from a start box into one of four corridors that they had seen a human enter with a bucket for baiting. They received a food reward for choosing the correct corridor. In unrewarded probe tests, the subjects' view of the corridors was blocked, but they could see a 'seeing' companion pig who had visual access to the baiting event, and another, whose view was also blocked, located in start boxes to their left and right. After the companions had been released and entered corridors, the subject was released and which companion it followed was recorded. Eight pigs followed companions less frequently than expected by chance, probably due to specific corridor or centre/side preferences. However, one subject showed no positional bias, and a significant preference for following the 'seeing' companion, consistent with the ability to take another's visual perspective. Our design rules out learning of a correct response during the experiment, by testing subjects in unrewarded probe trials, and by using companions that were equally trained and unaware of the subject's task. However, we cannot rule out the possibility that previously learned contingencies were used to solve the problem. We therefore consider that this apparent visual perspective taking ability does not necessarily imply any ability to understand knowledge states.

Cheap and Tight Bounds on the Solution Set of Perturbed Systems of Nonlinear Equations

This paper presents an iterative method for computing an outer interval bound on the solution set of parameters-dependent systems of non-linear equations for the case where the parameters take on their values within present intervals. The method is based on a recently suggested alternative linear interval enclosure of factorable non-linear functions in a given box. It comprises two stages: during the first stage, a relatively narrow starting box is determined using an appropriate inflation technique while the second stage aims at reducing the width of the starting box. Two algorithms implementing the method have been programmed in a C++ environment. Numerical examples seem to indicate that the second algorithm is rather efficient computation-wise. The method is self-validating: the fulfillment of a simple inclusion rule checked during its second stage ensures that the interval bound thus found is an outer approximation to the solution set of the perturbed system investigated.

Domestic chicks' runway responses to video images of conspecifics.

Because chickens are highly social animals, live conspecifics are often used to provide an incentive or goal in studies of gait, sociality or fear that require the bird to traverse a runway. However, the variable behaviour of the stimulus birds can influence the approach/avoidance responses of the test birds and thereby confound the results. Because chickens modify their behaviour readily and appropriately to a variety of video images, including social stimuli, we asked if video playback might represent easily controllable and standardized alternatives to live birds. Female ISA Brown chicks were housed in groups of eight and then exposed to a blank illuminated television for 10min per day from 2 to 7 days of age. At 8 or 9 days of age they were placed individually in the start box of a 1.6m long runway and we recorded their responses to a monitor displaying selected video images that was situated in the goal box at the opposite end of the runway. In Experiment 1 chicks approached a monitor playing the video image and soundtrack of feeding chicks significantly sooner than one of a goal box with the food dish and background noise. In Experiment 2, chicks were exposed to the same video of feeding conspecifics with or without the associated sounds or to a video of the goal box with or without the chick soundtrack. Both the videos of other chicks elicited faster approach than did those of the goal box and the sound and silent versions were equally attractive. Adding the soundtrack of feeding chicks to the goal-box video failed to increase its attractiveness. The present results suggest that chicks are attracted towards televised images of other chicks. They also indicate that the visual and auditory components of the video stimuli did not exert additive effects and that approach reflected attraction to the visual image. Collectively, our findings suggest that video playback of selected social stimuli, such as feeding conspecifics, could be a valuable tool in tests requiring voluntary locomotion along a predetermined path.

Dynamics of Hippocampal Ensemble Activity Realignment: Time versus Space

Whether hippocampal map realignment is coupled more strongly to position or time was studied in rats trained to shuttle on a linear track. The rats were required to run from a start box and to pause at a goal location at a fixed location relative to stable distal cues (room-aligned coordinate frame). The origin of each lap was varied by shifting the start box and track as a unit (box-aligned coordinate frame) along the direction of travel. As observed by Gothard et al. (1996a), on each lap the hippocampal activity realigned from a representation that was box-aligned to one that was room-aligned. We studied the dynamics of this transition using a measure of how well the moment-by-moment ensemble activity matched the expected activity given the location of the animal in each coordinate frame. The coherency ratio, defined as the ratio of the matches for the two coordinate systems, provides a quantitative measure of the ensemble activity alignment and was used to compare four possible descriptions of the realignment process. The elapsed time since leaving the box provided a better predictor of the occurrence of the transition than any of the three spatial parameters investigated, suggesting that the shift between coordinate systems is at least partially governed by a stochastic, time-dependent process.

Laying hen behavior 2. Cage type preference and heterophil to lymphocyte ratios

Studies were conducted to determine hen preference for and stress response to cage type. By using a plywood (1.25 cm) test apparatus with open- and solid-sided compartments and a plexiglass divider at the entrance for controlling passage, birds (n = 20) were evaluated as to their choice of compartment after training and acclimation. For each test, after training, an individual bird was placed in the start box and given 1 min to acclimate before making a choice. The experiment was repeated after rotating the apparatus 180 degrees. In Experiment 1, the open-sided compartment was chosen by 45% of the hens, and the solid-sided compartment by 25% (P = 0.02); 30% chose neither. In Experiment 2, the compartment with open sides was chosen by 70% of the hens, and that with solid sides was chosen by 15% (P = 0.004); 15% chose neither. The length of time required to choose one compartment over the other did not differ in either experiment (P = 0.29; P = 0.76). In Experiment 3, tests were videotaped from 0830 h to 1330 h, and tapes were scored for time spent in each compartment. Birds were observed to spend more time in open- compared with solid-sided compartments (P = 0.02). To assess stress level of birds exposed to each type of enclosure, blood was collected from 24 commercial Hy-Line W36 hens housed long-term in either open (n = 12) or solid (n = 12) cages, and heterophil:lymphocyte (H:L) ratios were determined. Birds in solid cages had higher H:L ratios than did birds in open cages (P = 0.02), indicating a greater stress response. These data would suggest that hens may prefer greater visual access to their surroundings afforded by open cages.

Visuomotor processing as reflected in the directional discharge of premotor and primary motor cortex neurons.

Premotor and primary motor cortical neuronal firing was studied in two monkeys during an instructed delay, pursuit tracking task. The task included a premovement "cue period," during which the target was presented at the periphery of the workspace and moved to the center of the workspace along one of eight directions at one of four constant speeds. The "track period" consisted of a visually guided, error-constrained arm movement during which the animal tracked the target as it moved from the central start box along a line to the opposite periphery of the workspace. Behaviorally, the animals tracked the required directions and speeds with highly constrained trajectories. The eye movements consisted of saccades to the target at the onset of the cue period, followed by smooth pursuit intermingled with saccades throughout the cue and track periods. Initially, an analysis of variance (ANOVA) was used to test for direction and period effects in the firing. Subsequently, a linear regression analysis was used to fit the average firing from the cue and track periods to a cosine model. Directional tuning as determined by a significant fit to the cosine model was a prominent feature of the discharge during both the cue and track periods. However, the directional tuning of the firing of a single cell was not always constant across the cue and track periods. Approximately one-half of the neurons had differences in their preferred directions (PDs) of >45 degrees between cue and track periods. The PD in the cue or track period was not dependent on the target speed. A second linear regression analysis based on calculation of the preferred direction in 20-ms bins (i.e., the PD trajectory) was used to examine on a finer time scale the temporal evolution of this change in directional tuning. The PD trajectories in the cue period were not straight but instead rotated over the workspace to align with the track period PD. Both clockwise and counterclockwise rotations occurred. The PD trajectories were relatively straight during most of the track period. The rotation and eventual convergence of the PD trajectories in the cue period to the preferred direction of the track period may reflect the transformation of visual information into motor commands. The widely dispersed PD trajectories in the cue period would allow targets to be detected over a wide spatial aperture. The convergence of the PD trajectories occurring at the cue-track transition may serve as a "Go" signal to move that was not explicitly supplied by the paradigm. Furthermore, the rotation and convergence of the PD trajectories may provide a mechanism for nonstandard mapping. Standard mapping refers to a sensorimotor transformation in which the stimulus is the object of the reach. Nonstandard mapping is the mapping of an arbitrary stimulus into an arbitrary movement. The shifts in the PD may allow relevant visual information from any direction to be transformed into an appropriate movement direction, providing a neural substrate for nonstandard stimulus-response mappings.

Yeast PKA represses Msn2p/Msn4p-dependent gene expression to regulate growth, stress response and glycogen accumulation.

Yeast cAMP-dependent protein kinase (PKA) activity is essential for growth and antagonizes induction of the general stress response as well as accumulation of glycogen stores. Previous studies have suggested that the PKA effects on the two latter processes result in part from transcription repression. Here we show that transcription derepression that accompanies PKA depletion is dependent upon the presence of two redundant Zn2+-finger transcription factors, Msn2p and Msn4p. The Msn2p and Msn4p proteins were shown previously to act as positive transcriptional factors in the stress response pathway, and our results suggest that Msn2p and Msn4p also mediate PKA-dependent effects on stress response as well as glycogen accumulation genes. Interestingly, PKA activity is dispensable in a strain lacking Msn2p and Msn4p activity. Thus, Msn2p and Msn4p may antagonize PKAdependent growth by stimulating expression of genes that inhibit growth. In agreement with this model, Msn2p/Msn4p function is required for expression of a gene, YAK1, previously shown to antagonize PKA-dependent growth. These results suggest that Msn2p/Msn4p-dependent gene expression may account for all, or at least most, of the pleiotropic effects of yeast PKA, including growth regulation, response to stress and carbohydrate store accumulation.