Table 1.

Using of Animal Models. Basic terminology used to describe how animal models and behavioral paradigms are classified, evaluated and used to assess social cognition.

Terminology	Type	Definition	Example
Animal model	Genotype based	Mice (in most cases) genetically engineered to contain genetic alterations either associated with ASD or causative of monogenic forms of ASD	FMR1 KO mouse (causative) DHCR7 KO mouse (causative) OTR KO mouse (associated) OT KO mouse (associated) CD38 KO mouse (associated)
Laboratory animals used to characterize a disease or the normative processes disrupted in a disease.
	Environment based	Animals (typically rodents or primates) that have undergone an environmental manipulation linked with ASD	Valproic acid treatment Borna disease virus infection Not discussed in this review
	Phenotype based	Animals social behavior parallels either functional or disordered human phenotypes	BTBRT +tf/J mice (disordered) BALB/c mice (disordered) Microtine rodents (functional) FMR1 KO mouse (high) DHCR7 KO mouse (high) OTR KO mouse (moderate) CD38 KO mouse (moderate) OT KO mouse (low)
Validity	Construct validity	Model replicates etiological or neurobiological bases of the human condition being represented
Relationship of the animal model or behavioral paradigm to the disease or behavior it is intended to represent.
	Predictive validity	The outcome of a manipulation in an animal model is indicative of the effect on the human condition	Partner preference in prairie voles (TBD) Social preference in mice (TBD)
	Face validity	The measured phenootypes in the model are phenomenologically similar to the human condition	Social recognition in OTRKO mice (disordered) Partner preference in prairie voles (functional)
Behavioral paradigm	Isolation induced vocalization	Frequency and intensity of ultrasonic vocalizations emitted by pups, when separated from their dams, is indicative of social anxiety	Wild-type mice ✔ OT KO mice ✖ OTR KO mice ✖ CD38 KO mice ✖ Wild-type mice ✔ Rats ✔ OT KO mice ✖ OTR KO mice ✖ CD38 KO mice ✖ Wild-type mice ✔ BTBR mice ✖ BALB/c ✖
An experimental test used to quantify a specific behavior in the laboratory, usually representative of an animal’s cognitive or emotional state.
	Social recognition test	Ability of a rodent to recall a familiar individual, as measured by decreased time spent in olfactory investigation of a familiar as opposed to novel conspecifics, as a measure of social memory
	Social preference test	Degree of preference expressed, as measure by time in proximity, to social vs. nonsocial and novel vs. familiar stimuli a proxy for social motivation
	Partner preference test	Formation of a social bond, as measured by twice as much time spent huddling with familiar as opposed to novel animal.	Prairie voles ✔ Meadow voles ✖

^✔indicates species typical performance in the behavioral task.

^✖indicates abnormal performance associated with social impairment.