Acetylcholine release in the hippocampus and prelimbic cortex during acquisition of a socially transmitted food preference

Interference with cholinergic functions in hippocampus and prefrontal cortex impairs learning and memory for social transmission of food preference, suggesting that acetylcholine (ACh) release in the two brain regions may be important for acquiring the food preference. This experiment examined release of ACh in the hippocampus and prefrontal cortex of rats during training for social transmission of food preference. After demonstrator rats ate a food with novel flavor and odor, a social transmission of food preference group of rats was allowed to interact with the demonstrators for 30 min, while in vivo microdialysis collected samples for later measurement of ACh release with HPLC methods. A social control group observed a demonstrator that had eaten food without novel flavor and odor. An odor control group was allowed to smell but not ingest food with novel odor. Rats in the social transmission but not control groups preferred the novel food on a trial 48 h later. ACh release in prefrontal cortex, with probes that primarily sampled prelimbic cortex, did not increase during acquisition of the social transmission of food preference, suggesting that training-initiated release of ACh in prelimbic cortex is not necessary for acquisition of the food preference. In contrast, ACh release in the hippocampus increased substantially (200%) upon exposure to a rat that had eaten the novel food. Release in the hippocampus increased significantly less (25%) upon exposure to a rat that had eaten normal food and did not increase significantly in the rats exposed to the novel odor; ACh release in the social transmission group was significantly greater than that of the either of the control groups. Thus, ACh release in the hippocampus but not prelimbic cortex distinguished well the social transmission vs. control conditions, suggesting that cholinergic mechanisms in the hippocampus but not prelimbic cortex are important for acquiring a socially transmitted food preference.     

Acetylcholine in the orbitofrontal cortex is necessary for the acquisition of a socially transmitted food preference

The social transmission of food preference task (STFP) has been used to examine the involvement of the hippocampus in learning and memory for a natural odor-odor association. However, cortical involvement in STFP has not been extensively studied. The orbitofrontal cortex (OFC) is important in odor-guided learning, and cholinergic depletion of the entire neocortex results in impairments in STFP. Here we examined the specific role of cholinergic modulation in the OFC by assessing the effect of 192 immunoglobulin G-saporin infusion directly into OFC prior to training on STFP. Cholinergic depletion in the OFC impaired expression of the socially transmitted odor association measured 2 d after training, indicating that cholinergic function in the OFC is essential for this form of associative learning.     

Hippocampal c-fos is necessary for long-term memory of a socially transmitted food preference

The present article examined the requirement of hippocampal c-Fos for learning a socially transmitted food preference (STFP). We reported previously that expression of the c-Fos protein is increased in the dorsal and ventral hippocampus of rats trained on the STFP (Countryman, Orlowski, Brightwell, Oskowitz, & Colombo, 2005). Pretraining intrahippocampal antisense to the immediate early gene c-fos was administered to adult male Long-Evans rats to determine if c-fos expression is necessary for either short- or long-term memory for STFP. Guide cannulae were implanted bilaterally into the dorsal hippocampus. Antisense oligodeoxynucleotides (ODNs) were administered unilaterally either 6.5, 8.5, 10.5, or 12.5 h prior to STFP training while either sense ODNs or saline were infused into the opposite hemisphere. Immunocytochemistry was performed, and cells showing c-Fos immunoreactivity (ir) were counted from the antisense-treated hemisphere and compared to cell counts from the control hemisphere. The results indicated significant suppression of learning-induced c-Fos protein at the 8.5 and 10.5 infusion-train intervals. Additional rats were implanted with cannulae into the dorsal and ventral hippocampus, and antisense ODNs, sense ODNs, or saline were administered bilaterally 8.5h prior to training. Rats were tested immediately and 14 days after training. Rats in all groups showed a significant preference for the demonstrated food at the short-term memory test. At the long-term memory test, however, rats infused with c-fos antisense showed no preference for the demonstrated food whereas rats infused with either sense or saline maintained their preference. The present findings suggest that c-fos is necessary for consolidation of non-spatial hippocampal-dependent memory.     

Excitotoxic lesions of the parafascicular nucleus produce deficits in a socially transmitted food preference

The parafascicular (PF) nucleus, a posterior component of the intralaminar nuclei of the thalamus, is considered to be an essential structure in the feedback circuits of basal ganglia-thalamo-cortical systems that critically participate in cognitive processes. To study the PF contribution to processing of behaviorally significant information during specific episodes of learning, we investigated the effects of damaging the PF nucleus in the acquisition of a natural form of social olfactory learning, the socially transmitted food preference (STFP) task. This task is a non-spatial paradigm that exhibits some of the characteristics of relational memory because it requires that animals use information obtained in one episode to guide later behavior in different circumstances. Adult male Wistar rats were submitted to pretraining bilateral N-methyl-D-aspartate (0.15 M, pH 7.4) lesions of the PF (0.4 microl/side, 0.2 microl/min). The behavioral effects of PF lesions were compared to vehicle- and sham-operated control groups and two retention delays were considered in separate groups: immediately (Lesion-I, Vehicle-I, and Sham-I groups) and 24h after training (Lesion-24, Vehicle-24, and Sham-24 groups). PF lesions produced delay-independent impairments in the STFP suggesting that this nucleus might modulate the acquisition of this odor-odor association task. Results are discussed in the context of medial prefrontal cortex deafferentation induced by PF damage.     

Temporary basolateral amygdala lesions disrupt acquisition of socially transmitted food preferences in rats

Lesions of the basolateral amygdala (BLA) have long been associated with abnormalities of taste-related behaviors and with failure in a variety of taste- and odor-related learning paradigms, including taste-potentiated odor aversion, conditioned taste preference, and conditioned taste aversion. Still, the general role of the amygdala in chemosensory learning remains somewhat controversial. In particular, it has been suggested that the amygdala may not be involved in a form of chemosensory learning that has recently received a substantial amount of study-socially transmitted food preference (STFP). Here, we provide evidence for this involvement by pharmacologically inactivating the basolateral amygdala bilaterally during STFP training. The same inactivation sites that impaired taste aversion learning eliminated the normally conditioned preference for a food smelled on a conspecific's breath. Impairments of learned preference persisted even in testing sessions in which BLA was not inactivated, and learning was normal when the BLA was inactivated only during testing sessions; thus, the impairment was a true acquisition deficit. In conjunction with previous results from other paradigms, therefore, our data suggest that the amygdala is vital for learning procedures involving pairings of potent and arbitrary chemosensory stimuli.     

Demonstration of a socially transmitted taste aversion in the rat

Observer rats were allowed to interact for 15 min with 2 conspecific demonstrators, 1 that had been fed a cocoa-flavored diet and 1 that had been fed a cinnamon-flavored diet. One of the demonstrators had been made ill immediately following ingestion of its diet. The observer rats were then presented with the cocoa-flavored and cinnamon-flavored diets for 22 h. The observer rats consumed significantly less of the ill demonstrator’s diet than of the healthy demonstrator’s diet. This finding suggests that, under some conditions, rats can acquire a socially transmitted taste aversion.     

Muscarinic transmission in the basolateral amygdala is necessary for the acquisition of socially transmitted food preferences in rats

We examined the involvement of muscarinic receptors in the basolateral amygdala (BLA) in the social transmission of food preference (STFP) learning by assessing the effects of scopolamine (20 microg/side), injected prior to social training, on a 24-h food-choice test. Muscarinic receptor blockade in the BLA significantly impaired STFP, as shown by the rats' chance preference for the odorized trained food. The present results are consistent with the suggestion that intact cholinergic transmission in the BLA is necessary for acquisition and/or initial consolidation and provide evidence that BLA integrity is part of the underlying circuit of STFP learning.     

Accumulation of c-fos mRNA in rat hippocampus during acquisition of a brightness discrimination

Training rats to attain a foot-shock-motivated brightness discrimination in a Y-maze results in an early and transient increase of hippocampal c-fos mRNA levels. Maximal accumulation was observed immediately after training, returning to basal levels during the following 2 h. A similar increase was obtained when rats were subjected to a pseudotraining with an equal number of runs, but with random pairing of the choice of bright and dark alleys with foot shock. It is suggested that induction of hippocampal c-fos mRNA expression is a necessary, but not sufficient, prerequisite for the formation of long-term memory trace. This early gene expression seems rather to correspond to an initial stage induced by complex stimulus presentation of both the training and the pseudotraining procedure. The subsequent late synthesis or processing of target proteins finally contributing to the formation of a permanent trace requires the action of further convergent signals to principal cells, probably mediating reward or emotional influences.     

The nature and acquisition of a preference for chili pepper by humans

This paper deals with the general problem of the acquisition of positive affective responses, by study of the reversal of an innate aversion to the irritant properties of chili pepper. Interviews, observations, and measurements were carried out in both Mexico and the United States. Exposure to gradually increasing levels of chili in food seems to be a sufficient condition for preference development. Chili likers are not insensitive to the irritation that it produces. They come to like the same burning sensation that deters animals and humans that dislike chili; there is a clear hedonic shift. This could be produced by association with positive events, including enhancement of the taste of bland foods, postingestional effects, or social rewards. It is also possible that the initial negative response to chili pepper is essential for the eventual liking. Chili stimulates an innate sensory “warning” system but is not harmful. The enjoyment of the irritation may result from the user's appreciation that the sensation and the body's defensive reaction to it are harmless. Eating of chili, riding on roller coasters, taking very hot baths, and many other human activities can be considered instances of thrill seeking or enjoyment of “constrained risks.” Evidence for and against various explanations of chili ingestion is presented.     

The value hypothesis and acquisition of preference in concurrent chains

Experiment 1 compared the acquisition of initial- and terminal-link responding in concurrent chains. The terminal-link schedules were fixed interval (FI) 10 sec and FI 20 sec, but some presentations were analogous to no-food trials in the peak procedure, lasting 60 sec with no reinforcement delivery. Pigeons completed a series of reversals in which the schedules signaled by the terminal-link stimuli (red and green on the center key) were changed. Acquisition of temporal control of terminal-link responding (as measured by peak location on no-food trials) was more rapid than acquisition of preference in the initial links. Experiment 2 compared acquisition in concurrent chains, using the typical procedure in which the terminal-link schedules are changed with a novel arrangement in which the initial-link key assignments were changed while the terminal-link schedules remained the same. Acquisition of preference was faster in the latter condition, in which the terminal-link stimulus-reinforcer relations were preserved. These experiments provide the first acquisition data that support the view that initial-link preference is determined by the values of the terminal-link stimuli.     

Fos expression in CRF-containing neurons in the rat paraventricular nucleus after central administration of neuromedin U

We examined the effects of centrally administered neuromedin U (NMU) on corticotrophin-releasing factor (CRF)-containing neurons in the hypothalamic paraventricular nucleus (PVN) of rats, using double immunohistochemistry for CRF and Fos. Almost all CRF-containing neurons in the parvocellular divisions of the PVN expressed Fos-like immunoreactivity 90 min after intracerebroventricular administration of NMU (3 nmol/rat). This results suggest the possibility that central NMU may be involved in stress-induced activation of CRF-containing neurons in the PVN.     

Fos protein expression in olfactory-related brain areas after learning and after reactivation of a slowly acquired olfactory discrimination task in the rat

Fos protein immunodetection was used to investigate the neuronal activation elicited in some olfactory-related areas after either learning of an olfactory discrimination task or its reactivation 10 d later. Trained rats (T) progressively acquired the association between one odor of a pair and water-reward in a four-arm maze. Two groups of pseudotrained rats were used: PO rats were not water restricted and were submitted to the olfactory stimuli in the maze without any reinforcement, whereas PW rats were water-deprived and systematically received water in the maze without any odorous stimulation. When the discrimination task was well mastered, a significantly lower Fos immunoreactivity was observed in T rats compared to PW and PO rats in most of the analyzed brain areas, which could reflect the post-acquisition consolidation process. Following memory reactivation, differences in Fos immunoreactivity between trained and some pseudotrained rats were found in the anterior part of piriform cortex, CA3, and orbitofrontal cortex. We also observed that Fos labeling was significantly higher in trained rats after memory reactivation than after acquisition of the olfactory task in most of the brain areas examined. Our results support the assumption of a differential involvement of neuronal networks after either learning or reactivation of an olfactory discrimination task.     

The effect of adrenalectomy on Fos expression in vasopressinergic and oxytocinergic neurons in response to stress in the rat

This study evaluated the responses of vasopressin (AVP) and oxytocin (OT) neurons to alterations in hypothalamo-pituitary axis activity by adrenalectomy (ADX) or after restraint stress compared with basal conditions. Wistar male rats were perfuse-fixed by cardiac perfusion under anesthesia 3 h, 1, 3 and 14 days after ADX or Sham surgery. Coronal hypothalamic sections were used for evaluation of Fos, AVP and OT expression by immunohistochemistry. Under basal conditions and after stress, Fos-AVP double labeling showed no difference in the magnocellular subdivisions of the paraventricular nuclei (PVN) or in the supraoptic nuclei (SON), suggesting that the magnocellular AVP system is unlikely to contribute to ACTH secretion after restraint in both Sham and ADX rats. Fos-AVP double labeling in the parvocellular medial paraventricular nucleus (PaMP) in ADX groups was increased after 3 h in basal conditions, and in all periods after restraint stress. There were no differences between Sham and ADX groups in Fos-OT double labeling in any subdivision of the PVN; however, in the SON, the number of Fos-OT double labeled cells was increased at all time-points after stress in the ADX group. Fos expression was increased in the PaMP after 3 h and after restraint stress in the Sham and ADX groups, especially in the ADX group. In conclusion, Fos expression in different cell populations of the PVN can be differentially regulated by short- and long-term absence of glucocorticoid negative feedback and also by stress-related excitatory and/or inhibitory neural inputs. The Fos-AVP double labeling findings in the PaMP also indicate a minor participation of these vasopressinergic neurons in the regulation of the HPA axis after ADX.     

Muscarinic cholinergic receptor blockade in the rat prelimbic cortex impairs the social transmission of food preference

Previous findings demonstrate the involvement of the cholinergic NBM in the acquisition of the social transmission of food preference (STFP), a relational associative odor-guided learning task. There is also evidence that muscarinic receptors in the medial prefrontal cortex, an important NBM target area, may modulate olfactory associative memory. The present experiment determined the consequences of blocking muscarinic cholinergic receptors in a component of the medial prefrontal region (the prelimbic cortex) on the STFP task. Adult male Wistar rats were bilaterally infused with scopolamine (20 microg/site) prior to training and showed a severe impairment in the expression of the task measured in two retention sessions, both immediately and 24h after training. Local scopolamine injections in the prelimbic cortex did not affect other behavioral measures such as olfactory perception, social interaction, motivation to eat, neophobia, or exploration. Results suggest that muscarinic transmission in the prelimbic cortex is essential for the STFP, supporting the hypothesis that ACh in a specific prefrontal area is important for this naturalistic form of olfactory relational memory. Current data are discussed in the context of disruption of learning as a result of interferences in PLC functions such as behavioral flexibility, attention, and strategic planning.