Fred Westbrook

What the rat's nose tells the rat's mouth: Long delay aversion conditioning with aqueous odors and potentiation of taste by odors

In Experiment 1, olfactory bulbectomized and control rats were trained using operant conditioning to determine the taste threshold of aqueous amyl acetate. Concentrations below gustatory threshold were used in Experiments 2–5 to compare the effectiveness of odors with various concentrations of saccharin as cues for illness. The results showed the following: (1) The effectiveness of odor and taste was directly related to concentration; (2) the strength of an aversion to a concentration of taste could be matched by an appropriate concentration of an odor; (3) odor was as effective as taste with CS-US delays of 4 h; and (4) an effective odor potentiated an aversion to an otherwise ineffective taste. The results challenge the privileged role accorded tastes in food aversion learning and the manner in which tastes are held to interact with odors according to the sensory-and-gate channeling analysis of potentiation (Rusiniak, Hankins, Garcia, & Brett, 1979).

Neurological and stress related effects of shifting obese rats from a palatable diet to chow and lean rats from chow to a palatable diet.

Rats exposed to an energy rich, cafeteria diet overeat and become obese. The present experiment examined the neural and behavioural effects of shifting obese rats from this diet to chow and lean rats from chow to the cafeteria diet. Two groups of male Sprague Dawley rats (n=24) were fed either highly palatable cafeteria diet or regular chow (30% vs. 12% energy as fat) for 16 weeks. Half of each group (n=12) was then switched to the opposing diet while the remainder continued on their original diet. The effects of diet switch on the response to restraint stress were assessed and rats were euthanised nine days after diet reversal. After 16 weeks of cafeteria diet, rats were 27% heavier than controls. Rats switched from chow to cafeteria diet (Ch-Caf) became hyperphagic and had increased dopamine D1, D2 and tyrosine hydroxylase mRNA expression in the ventral tegmental area (VTA) compared to rats switched from cafeteria to chow (Caf-Ch). Caf-Ch rats were hypophagic with significant reductions in white (16%) and brown (32%) adipose tissue mass, plasma leptin (34%) and fasting glucose (22%) compared to rats remaining on the cafeteria diet (Caf-Caf). Caf-Caf rats had an elevated plasma corticosterone response to restraint stress compared to Ch-Caf rats indicating that acute but not chronic consumption of palatable cafeteria diet may protect against stress. Caf-Ch rats had increased corticotropin releasing hormone mRNA expression in the dorsal hypothalamus compared to Ch-Ch rats implying that removal of the palatable diet activated the HPA axis. The results were discussed in terms of the links between palatability of diet, obesity and stress.

Dynamics of pre- and post-choice behaviour: rats approximate optimal strategy in a discrete-trial decision task

We simulate two types of environments to investigate how closely rats approximate optimal foraging. Rats initiated a trial where they chose between two spouts for sucrose, which was delivered at distinct probabilities. The discrete trial procedure used allowed us to observe the relationship between choice proportions, response latencies and obtained rewards. Our results show that rats approximate the optimal strategy across a range of environments that differ in the average probability of reward as well as the dynamics of the depletion-renewal cycle. We found that the constituent components of a single choice differentially reflect environmental contingencies. Post-choice behaviour, measured as the duration of time rats spent licking at the spouts on unrewarded trials, was the most sensitive index of environmental variables, adjusting most rapidly to changes in the environment. These findings have implications for the role of confidence in choice outcomes for guiding future choices.

Danger changes the way the mammalian brain stores information about innocuous events: a study of sensory preconditioning in rats

Abstract The amygdala is a critical substrate for learning about cues that signal danger. Less is known about its role in processing innocuous or background information. The present study addressed this question using a sensory preconditioning protocol in male rats. In each experiment, rats were exposed to pairings of two innocuous stimuli in stage 1, S2 and S1, and then to pairings of S1 and shock in stage 2. As a consequence of this training, control rats displayed defensive reactions (freezing) when tested with both S2 and S1. The freezing to S2 is a product of two associations formed in training: an S2-S1 association in stage 1 and an S1-shock association in stage 2. We examined the roles of two medial temporal lobe (MTL) structures in consolidation of the S2-S1 association: the perirhinal cortex (PRh) and basolateral complex of the amygdala (BLA). When the S2-S1 association formed in a safe context, its consolidation required neuronal activity in the PRh (but not BLA), including activation of AMPA receptors and MAPK signaling. In contrast, when the S2-S1 association formed in a dangerous context, or when the context was rendered dangerous immediately after the association had formed, its consolidation required neuronal activity in the BLA (but not PRh), including activation of AMPA receptors and MAPK signaling. These roles of the PRh and BLA show that danger changes the way the mammalian brain stores information about innocuous events. They are discussed with respect to danger-induced changes in stimulus processing.

Behavioral correlates of the decision process in a dynamic environment: post-choice latencies reflect relative value and choice evaluation

One characteristic of natural environments is that outcomes vary across time. Animals need to adapt to these environmental changes and adjust their choices accordingly. In this experiment, we investigated the sensitivity with which rats could detect, and adapt to, multiple changes in the environment. Rats chose between two spouts which delivered 5% sucrose rewards with distinct probabilities. Across three phases, reward probabilities changed in size (large or small) and direction (increase or decrease). A discrete trial-structure was used, which allowed the choice process to be decomposed into three distinct response latency measures (choice execution latency, spout sampling duration, and trial-initiation latency). We found that a large decrease in reward probabilities rapidly produced the greatest change in choice proportions. The time taken to execute a choice reflected the differences in reward probabilities across the two spouts in some cases, but also reflected training history. By contrast, the amount of time rats spent responding at reward spouts in anticipation of reward consistently reflected the relative likelihood of reward across the two spouts and not the absolute probability of reward. The latency to initiate the subsequent trial reflected choice evaluation. These three response latencies thus indexed key behavioral correlates of the choice process as it unfolds in time. We discuss how this paradigm can be used to assess the corresponding neural correlates of decision-making.

Temporal dynamics of choice behavior in rats and humans: an examination of pre- and post-choice latencies

Identifying similarities and differences in choice behavior across species is informative about how basic mechanisms give rise to more complex processes. In the present study, we compared pre- and post-choice latencies between rats and humans under two paradigms. In Experiment 1, we used a cued choice paradigm where subjects were presented with a cue that directed them as to which of two options to respond for rewards. In Experiment 2, subjects were free to choose between two options in order to procure rewards. In both Experiments rewards were delivered with distinct probabilities. The trial structure used in these experiments allowed the choice process to be decomposed into pre- and post-choice processes. Overall, post-choice latencies reflected the difference in reward probability between the two options, where latencies for the option with higher probability of reward were longer than those for the option with lower probability of reward. An interesting difference between rats and humans was observed: the choice behavior for humans, but not rats, was sensitive to the free-choice aspect of the tasks, such that in free-choice trials post-choice latencies no longer reflected the difference in reward probabilities between the two options.

P2-470: Survival and differentiation of adult skin-derived neuroprecursors in a rat model of age-related cognitive impairment

mer s disease (AD). Up to now no resolutive pharmacological therapy exists and there are increasing arguments regarding the beneficial effect of natural nutrients, able to slow down the progression of the disease. Some have the ability to induce cell proliferation and/or survival. Adult neurogenesis could be a good therapeutic strategy for cognitive aging and neurodegenerative diseases(AD). The aims of this work has been to study the modulatory effect of *LMN diet (cocoa, nuts and other natural extracts) in adult mouse neurogenic brain areas. Methods: 129SV male mice, were feed during 40 days with a standard Harlan 2014 control diet and the same diet containing 9,27% of *LMN. Animals received BrdU injections. Brains were processed for inmunohistological and immunoblots studies. Results: Histological samples of mice feed with *LMN diet, showed a noticeable increasing number of proliferative cells by BrdU and PCNA staining, in the adult neurogenic areas: subventricular zone (SVZ) and subgranular layer of dentate gyrus (sgDG). Using Dcx and PSA-NCAM, an increasing in the undifferentiating neurons were determined in the granular layer of dentate gyrus and in the rostral migratory stream (RMS). The immature oligodendrocytes (Ng2) and astrocytes (GFAP) were also increasing in these brain areas. All these results were corroborated by Western-Blot analysis. Moreover, the several interneurons subpopulations of the olfactory bulb were changed. Increasing the tyrosine hydroxylase, calretinin and calbindin neuronal subpopulations, and decreasing the parvalbumin interneurons. In the dentate gyrus, the granular layer presented a high cell number when comparing with the control animals. Conclusions: All these findings showed that *LMN diet promotes the neurogenesis in the adult mouse neurogenic niches. The differences between interneurons subpopulations of olfactory bulb suggested that, *LMN diet could modulate differentiation process in the RMS. Therefore, *LMN diet could be a promising nutrient that would contribute to the neural replacement and to re-establish the brain function in order to avoid the cognitive decline, the main hallmark in Alzheimer’s disease. *Patent submitted: Reference ES2281270. Acknowledgements: This work has been financed by the Spanish Ministry of Industry, project INGENIO 2010CENIT ref MET-DEV-FUN (2006-2009).