Assessment of Social Transmission of Food Preferences Behaviors

Olfactory recognition deficits are suggested to serve as clinical marker to differentiate Alzheimer's disease (AD) subjects from normal aging groups^1,2,3,4. A range of neuropsychiatric disorders are characterized by disturbances in olfactory recognition and memory, including AD and Parkinson's^5,6. Several behavioral tests and protocols have been established to assess olfactory recognition and discrimination in animal models⁷. As such, translational research using appropriate and validated animal models and tests for olfactory memory may advance better diagnosis and treatment for neurodegenerative disorders. Therefore, the social transmission of food preference (STFP) test that was originally invented in the early 80's⁸ was adapted. In this task, animals are evaluated on their innate ability to learn about food safety from their conspecifics. Underlying select-reject decision, processes involve assessment of the sensory characteristics of the food and an animal must be able to review and ingrate different features (i.e., taste and odor).

The STFP test consists of a rather simple phenomenon: after interaction of the naive 'observer' rodent with a 'demonstrator' that previously consumed a food, the observer normally demonstrates a greater preference for this food^8,9,10. Analyzing necessary conditions resulting in this preference, showed that direct subject – demonstrator exposure (eaten or dusted with a food) is enough to boost the observer's preference. However, purely smelling nor eating a food are not sufficient to induce this type of preference^11,12.

The STFP protocol consists of four steps over five days. The first step consists of increasing the motivation of the animals to make them eat a novel food. To do so, all rodents are put on a 23-h, food-deprivation schedule, receiving regular chow for 1 h/day for two consecutive days. In the second step, the priming phase, each demonstrator is provided for 1 h with food containing a novel flavor (chow mixed with either cocoa or cinnamon in the original experiments). In the third step, the social interaction phase, each demonstrator is placed into the cage of a subject observer rodent for 30 min. In the fourth step, 24 h after the social interaction, each subject is offered the choice of both flavored diets. The observer's intake of both foods and preference percentages of both diets eaten by the subject are assessed.

Selective neurotoxic lesions of hippocampus-subiculum are shown to impair performance on this task¹³. Also, mutations affecting hippocampal function in mice have been reported to prevent food preferences^14,15,16,17. Importantly, STFP performance does not exclusively rely on proper hippocampal functioning. It was reported in several pharmacological, genetic manipulations, and lesion studies that other brain structures beside hippocampus may play a role in mediating different aspects of socially-induced diet choice learning and memory. For instance, cholinergic neurons of the medial septum/vertical limb of the diagonal band or nucleus basalis magnocellularis/substantia innominata are suggested to possess different roles in acquiring and retrieving non-spatial social memory of olfactory cues¹⁸. Furthermore, orbitofrontal cortex has been implicated in odor-guided learning, and cholinergic depletion of the entire neocortex resulted in STFP deficits, indicating that these brain regions are essential for this type of associative learning¹⁹.

Possible confounding factors were avoided as much as possible, such as spreading of the odors or dragging of the food outside the cups. An additional habituation step to the apparatus and a supplementary test before the actual STFP task were added, to assess if the rodents can actually smell and are willing to eat novel foods, the buried cookie test²⁰. Also, by including automated video-tracking, the time spent exploring both the demonstrator during the social interaction as well as the food during the test phase could also be measured. The exploration of the path for each subject is recorded using a camera connected to a video tracking-software equipped computer. As such, different aspects of exploration performance, such as time in each zone, and number of zone visits can be calculated. This gives more detailed information about the animals' activity during the test phase, besides the amount of consumed food as in the original STFP protocol.

In previous experiments with an AD mouse model, the THY-Tau22 model, it was found that impairment in this STFP memory from the age of 9-10 months could be picked up, and these co-occurred with deficits in hippocampal synaptic plasticity and tau pathology in the hippocampus¹⁶. Since tau pathology occurs late in disease progression, according to the amyloid cascade hypothesis after the disposition of amyloidal plaques²¹, it was hypothesized that STFP deficits could be detected at an earlier age in amyloid transgenic mice. Therefore, the STFP test was applied in 3 months old APP/PS1 mice²², the most common used model of AD. This type of socially-induced food choice was indeed found to be impaired in the APP/PS1 mice. It is important that these mice, at least at this age, were devoid of general olfactory, locomotor, or social exploration impairments. To conclude, olfactory recognition dysfunction could be an important early screening method for AD in humans and mice alike. This reliable, cheap and easy screening for early AD could be useful for therapeutic research. If we could screen for early AD more effectively, we could interfere earlier on in the disease process.