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.     

Time-courses of Fos expression in rat hippocampus and neocortex following acquisition and recall of a socially transmitted food preference

The present study examined expression of the immediate-early gene, c-Fos, following acquisition, 48-h (recent) recall, and 1-week (remote) recall of a socially transmitted food preference (STFP) in multiple brain regions implicated in learning and memory. In comparisons with controls, trained Long-Evans rats had increased Fos immunoreactivity in the ventral hippocampus following acquisition and recent recall. In the parahippocampal cortices, Fos was increased in the lateral entorhinal cortex after acquisition. In the orbitofrontal cortex, increased Fos immunoreactivity was observed in the lateral orbital cortex following both recent and remote recall and in the ventral orbital cortex following remote recall, indicating a role for the orbitofrontal cortex in the remote recall of STFP memory. In contrast, in the medial prefrontal cortex, increased Fos-ir was found following acquisition in the prelimbic cortex and following recent recall in the prelimbic and infralimbic cortices. No differences in Fos expression were found between trained rats and controls in the dorsal hippocampus, posterior parietal cortex, or amygdala. The present findings support a time-limited role of the hippocampus in the acquisition and recall of STFP memory and implicate neocortical regions involved in STFP acquisition, recent, and remote recall.     

Male Wistar rats show individual differences in an animal model of conformity

Conformity refers to the act of changing one’s behaviour to match that of others. Recent studies in humans have shown that individual differences exist in conformity and that these differences are related to differences in neuronal activity. To understand the neuronal mechanisms in more detail, animal tests to assess conformity are needed. Here, we used a test of conformity in rats that has previously been evaluated in female, but not male, rats and assessed the nature of individual differences in conformity. Male Wistar rats were given the opportunity to learn that two diets differed in palatability. They were subsequently exposed to a demonstrator that had consumed the less palatable food. Thereafter, they were exposed to the same diets again. Just like female rats, male rats decreased their preference for the more palatable food after interaction with demonstrator rats that had eaten the less palatable food. Individual differences existed for this shift, which were only weakly related to an interaction between their own initial preference and the amount consumed by the demonstrator rat. The data show that this conformity test in rats is a promising tool to study the neurobiology of conformity.     

Social transmission and memory of food preferences in pine voles (Microtus pinetorum)

The social transmission of food preferences is affected by factors including the length of time a preference is maintained. The authors investigated the social transmission of food preferences in pine voles (Microtus pinetorum) and whether food items had to be present for memory to persist. A demonstrator vole was fed cocoa-flavored food, a nonpreferred food. After interacting with a demonstrator vole, observer voles preferred cocoa-flavored food as compared with either naive voles that had not interacted with demonstrators or voles that had been exposed to odors. Observers retained this preference for 72 hr after interacting with an observer whether or not flavored foods were present. The ability to learn which food items are palatable and safe may benefit a generalist herbivore that has faced selection to avoid toxic baits.     

Social interaction modifies learned aversions, sodium appetite, and both palatability and handling-time induced dietary preference in rats (Rattus norvegicus)

In a series of four experiments, I examined the extent to which socially transmitted diet preference could counteract the effects of a learned aversion (Experiment 1), a palatability-based diet preference (Experiment 2), a polyethylene glycol 20,000-induced sodium appetite (Experiment 3), and a handling-time induced dietary preference (Experiment 4). I found that rats poisoned after eating a novel diet ate very substantial amounts of the averted diet following interaction with conspecifics that had eaten the averted diet. Following interaction with conspecifics that had eaten an unpalatable diet, rats offered a choice between palatable and unpalatable diets ate more than twice as much unpalatable diet as did controls lacking social experience. Sodium-deficient rats offered a choice between sodium-enriched and sodium-adequate diets ate less than half as much sodium-enriched diet, following interaction with conspecifics that had eaten sodium-adequate diet as did control rats lacking social experience. Rats offered a choice between isocaloric, roughly equipalatable foods with long and short handling times (e.g., sunflower seeds with and without shells) chose the food having the longer handling time after interacting with conspecifics eating that food. These findings suggest that social influence is a major factor in guiding diet selection by rats.     

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.     

Protein deficiency magnifies social influence on the food choices of Norway rats (Rattus norvegicus)

The food choices of protein-deprived juvenile rats were more profoundly affected by interaction with conspecifics than were the food choices of protein-replete juvenile rats. When choosing among four different-flavored, protein-deficient diets, protein-deprived rats ate significantly more of the diet eaten by a conspecific demonstrator than did protein-replete rats. These data suggest that the food choices of the relatively less successful members of a population are most affected by social interaction. Consequently, the mean effect of social interaction on diet selection in a population of Norway rats is likely to be positive.     

Differential involvement of prefrontal cortex,striatum, and hippocampus in DRL performance in mice

Behavioral effects of neurotoxic lesions of the hippocampus, medial prefrontal (prelimbic, infralimbic and anterior cingulate) cortex or dorsal striatum were assessed using a DRL-10s schedule in mice. Post-operative acquisition data indicate that mice with hippocampal, but not prefrontal or striatal lesions received fewer reinforcements during daily 30-min sessions, and were less efficient in the timing of their responses. Additional analysis of inter-response-time (IRT) distributions revealed that the responses of hippocampal-lesioned mice exhibited undistinguishable responses for short IRTs (up to 9s). In addition, prefrontal-lesioned mice demonstrated a degradation of performance with further testing, and a flattened IRT distribution at late test phase, while striatal-lesioned mice behaved similarly to sham-lesioned mice. These results are interpreted in terms of known functions of the hippocampus in behavioral inhibition, and of the prefrontal cortex in executive control/decision making (and time production).     

Social learning of food types in zebra finches (<Emphasis Type="Italic">Taenopygia guttata</Emphasis>) is directed by demonstrator sex and feeding activity

In this study we examined how social learning of feeding preferences by zebra finches was affected by the identity of different demonstrators. We presented adult zebra finches with two demonstrators, one male and one female, that exhibited different food choices, and we recorded their subsequent preference when given a choice between the two food types. Previously it was found that young zebra finches' patterns of social learning are affected by the sex of the individual demonstrating a feeding behaviour. This result could be explained by the lack of exposure these animals had to the opposite sex, or by their mating status. Therefore, we investigated the social learning preferences of adult mated zebra finches. We found the same pattern of directed social learning of a different type of feeding behaviour (food colour): female zebra finches preferred the colour of food eaten by male demonstrators, whereas male zebra finches showed little evidence of any preference for the colour of food eaten by female demonstrators. Furthermore, we found that female observers' preferences were biased by demonstrators' relative feeding activity: the female demonstrator was only ever preferred if it ate less than its male counterpart. Electronic Publication     

Diencephalic damage decreases hippocampal acetylcholine release during spontaneous alternation testing

A rodent model of diencephalic amnesia, pyrithiamine-induced thiamine deficiency (PTD), was used to investigate diencephalic-hippocampal interactions. Acetylcholine (ACh) release, a marker of memory-related activation, was measured in the hippocampus of PTD-treated and control rats prior to, during, and after spontaneous alternation test. During behavioral testing, all animals displayed increases in ACh release. However, both the percent increase of ACh release during spontaneous alternation testing and the alternation scores were higher in control rats relative to PTD-treated rats. Thus, when rats are tested on a task with demands dependent on the hippocampus, it appears that the hippocampus is not fully activated after diencephalic damage.     

Effects of rodent prefrontal lesions on object-based, visual scene memory

It has been suggested that certain prefrontal areas contribute to a neural circuit that mediates visual object memory. Using a successive go/no-go visual scene discrimination task, object-based long-term memory was assessed in two rodent prefrontal regions. Rewarded trials consisted of a standard scene of four toy objects placed over baited food wells. The objects and their locations composing the standard scene remained constant for the duration of the study. Trials in which one of the standard scene objects was replaced with a novel object were not rewarded. Following the establishment of a significant difference between latency to approach the rewarded standard scene compared to latency to approach non-rewarded scenes, quinolinic acid or control vehicle was infused into either the prelimbic and infralimbic cortices or the anterior cingulate cortex. Following a 1 week recovery period, subjects were retested. Animals with prelimbic/infralimbic cortex lesions displayed a profound and sustained deficit, whereas, animals with anterior cingulate cortex lesions showed a slight initial impairment but eventually recovered. Both lesion groups acquired a simple single object discrimination task as quickly as controls indicating that the deficits on the original scene discrimination task were not due to motivational, response inhibition, or perceptual problems.     

Effects of excitotoxic brain lesions on taste-mediated odor learning in the rat

The association learning between taste and odor is important in ingestive behavior. For a better understanding of this learning, we have developed a convenient and useful paradigm to assess the taste-mediated odor learning. In the training session, Wistar male rats drank water from two bottles in their home cages and from eight small glass dishes. In the learning session they were exposed in their home cages and also in a circular open-field apparatus to 0.005 M Na-saccharin and 0.02 M quinine hydrochloride which contained either banana or almond odors. One learning trial consisted of this pair of exposures. The preceding behavioral experiment has shown that these two odors are not aversive and are differentially perceived by rats. In the test session, the animals were put in the open-field apparatus equipped with eight dishes: four contained water with banana, and another four, with almond. Normal control rats preferred to drink water with the odor previously associated with saccharin. Stronger and more persistent preference was attained after two or three learning trials. To elucidate the brain sites responsible for this taste-mediated odor learning, the same procedure was assessed on brain-lesioned rats. Rats with lesions in the amygdala showed rapid extinction of preference to the saccharin-associated odor, whereas control rats did not. However, rats with lesions in the insular cortex showed retention of learning similar to that of the control rats. Rats with lesions in the sulcal prefrontal or cingulate cortices showed moderate disruptive effects on preference to the saccharin-associated odor. In conclusion, the odor learning established in our experimental paradigm is based on the association between the quality of odor and hedonics of taste. The amygdala may play a role in the formation, at least in the retention process, of this taste-odor association learning.     

Opposing effects on muscarinic acetylcholine receptors in the piriform cortex of odor-trained rats

We combined pharmacological studies and electrophysiological recordings to investigate modifications in muscarinic acetylcholine (ACh) receptors (mAChR) in the rat olfactory (piriform) cortex, following odor-discrimination rule learning. Rats were trained to discriminate between positive and negative cues in pairs of odors, until they reached a phase of high capability to learn unfamiliar odors, using the same paradigm (“rule learning”). It has been reported that at 1–3 d after the acquisition of odor-discrimination rule learning, pyramidal neurons in the rat piriform cortex show enhanced excitability, due to a reduction in the spike-activated potassium current I_AHP, which is modulated by ACh. Further, ACh and its analog, carbachol (CCh), lost the ability to reduce the I_AHP in neurons from trained rats. Here we show that the reduced sensitivity to CCh in the piriform cortex results from a decrease in the number of mAChRs, as well as a reduction in the affinity of the receptors to CCh. Also, it has been reported that 3–8 d after the acquisition of odor-discrimination rule learning, synaptic transmission in the piriform cortex is enhanced, and paired-pulse facilitation (PPF) in response to twin stimulations is reduced. Here, intracellular recordings from pyramidal neurons show that CCh increases PPF in the piriform cortex from odor-trained rats more than in control rats, suggesting enhanced effect of ACh in inhibiting presynaptic glutamate release after odor training.     

Short-term estrogen treatment in ovariectomized rats augments hippocampal acetylcholine release during place learning

Estrogen modulates learning and memory in ovariectomized and naturally cycling female rats, especially in tasks using spatial learning and navigation. Estrogen also modulates cholinergic function in various forebrain structures. Past studies have shown positive correlations between hippocampal ACh output and performance on hippocampus-dependent tasks. The present study examined whether estradiol replacement would potentiate hippocampal ACh release during place learning. In vivo microdialysis and HPLC were used to measure extracellular ACh levels in the hippocampus of ovariectomized female rats that had received s.c. injections of 17beta-estradiol (10 microg) or sesame oil (vehicle treatment) 48 and 24h prior to training on a place task. Estrogen did not alter baseline levels of extracellular ACh in the hippocampus. During training, hippocampal ACh increased in ovariectomized rats regardless of estrogen status. However, while estradiol did not enhance learning in this experiment, estradiol significantly potentiated the increase in hippocampal ACh release seen during place training. This represents the first demonstration of on-line assessment of ACh output in hippocampus during learning in female rats and suggests that estrogen-dependent modulation of ACh release during training might control activation of different neural systems used during learning.     

Responses of observer rats (Rattus norvegicus) to complex, diet-related signals emitted by demonstrator rats

We explored the effects of complex, food-identifying signals emitted by demonstrator Long-Evans rats (Rattus norvegicus) on food preferences of their observers. In Experiments 1 and 2, observers identified each of 2 or 3 foods their demonstrators had eaten before interacting with observers. In Experiment 3, individual observers interacted with groups of demonstrators. Some of these demonstrators had eaten one food, some another. Observers then chose between the two foods. The greater the proportion of demonstrators in a group that had eaten a diet, the greater the proportion of that diet the observers ate. In Experiment 4, each observer interacted over several weeks with a series of demonstrators and preferred each of the foods its demonstrators had eaten. In sum, the food preferences of observers were affected by several different types of complex, food-identifying signals like those one might expect rats to encounter outside the laboratory.     

Acetylcholine release in the hippocampus and striatum during place and response training

These experiments examined the release of acetylcholine in the hippocampus and striatum when rats were trained, within single sessions, on place or response versions of food-rewarded mazes. Microdialysis samples of extra-cellular fluid were collected from the hippocampus and striatum at 5-min increments before, during, and after training. These samples were later analyzed for ACh content using HPLC methods. In Experiment 1, ACh release in both the hippocampus and striatum increased during training on both the place and response tasks. The magnitude of increase of training-related ACh release in the striatum was greater in rats trained on the response task than in rats trained on the place task, while the magnitude of ACh release in the hippocampus was comparable in the two tasks. Experiment 2 tested the possibility that the hippocampus was engaged and participated in learning the response task, as well as the place task, because of the availability of extra-maze cues. Rats were trained on a response version of a maze under either cue-rich or cue-poor conditions. The findings indicate that ACh release in the hippocampus increased similarly under both cue conditions, but declined during training on the cue-poor condition, when spatial processing by the hippocampus would not be suitable for solving the maze. In addition, high baseline levels of ACh release in the hippocampus predicted rapid learning in the cue-rich condition and slow learning in the cue-poor condition. These findings suggest that ACh release in the hippocampus augments response learning when extra-maze cues can be used to solve the maze but impairs response learning when extra-maze cues are not available for use in solving the maze.     

Imitation and affordance learning by pigeons (Columba livia)

The bidirectional control procedure was used to determine whether pigeons (Columba livia) would imitate a demonstrator that pushed a sliding screen for food. One group of observers saw a trained demonstrator push a sliding screen door with its beak (imitation group), whereas 2 other groups watched the screen move independently (possibly learning how the environment works) with a conspecific either present (affordance learning with social facilitation) or absent (affordance learning alone). A 4th group could not see the screen being pushed (sound and odor control). Imitation was evidenced by the finding that pigeons that saw a demonstrator push the screen made a higher proportion of matching screen pushes than observers in 2 appropriate control conditions. Further, observers that watched a screen move without a demonstrator present made a significantly higher proportion of matching screen pushes than would be expected by chance. Thus, these pigeons were capable of affordance learning.     

Differential acetylcholine release in the prefrontal cortex and hippocampus during pavlovian trace and delay conditioning

Pavlovian trace conditioning critically depends on the medial prefrontal cortex (mPFC) and hippocampus (HPC), whereas delay conditioning does not depend on these brain structures. Given that the cholinergic basal forebrain system modulates activity in both the mPFC and HPC, it was reasoned that the level of acetylcholine (ACh) release in these regions would show distinct profiles during testing in trace and delay conditioning paradigms. To test this assumption, microdialysis probes were implanted unilaterally into the mPFC and HPC of rats that were pre-trained in appetitive trace and delay conditioning paradigms using different conditional stimuli in the two tasks. On the day of microdialysis testing, dialysate samples were collected during a quiet baseline interval before trials were initiated, and again during performance in separate blocks of trace and delay conditioning trials in each animal. ACh levels were quantified using high-performance liquid chromatography and electrochemical detection techniques. Consistent with our hypothesis, results showed that ACh release in the mPFC was greater during trace conditioning than during delay conditioning. The level of ACh released during trace conditioning in the HPC was also greater than the levels observed during delay conditioning. While ACh efflux in both the mPFC and HPC selectively increased during trace conditioning, ACh levels in the mPFC during trace conditioning testing showed the greatest increases observed. These results demonstrate a dissociation in cholinergic activation of the mPFC and HPC during performance in trace but not delay appetitive conditioning, where this cholinergic activity may contribute to attentional mechanisms, adaptive response timing, or memory consolidation necessary for successful trace conditioning.