The BTBR T+tf/J inbred mouse strain displays a variety of persistent phenotypic alterations similar to those exhibited in autism spectrum disorders (ASDs). The unique genetic background of the BTBR strain is thought to underlie its lack of reciprocal social interactions, elevated repetitive self-directed grooming, and restricted exploratory behaviors. In order to clarify the existence, range, and mechanisms of abnormal repetitive behaviors within BTBR mice, we performed detailed analyses of the microstructure of self-grooming patterns and noted increased overall grooming, higher percentages of interruptions in grooming bouts and a concomitant decrease in the proportion of incorrect sequence transitions compared to C57BL/6J inbred mice. Analyses of active phase home-cage behavior also revealed an increase in stereotypic bar-biting behavior in the BTBR strain relative to B6 mice. Finally, in a novel object investigation task, the BTBR mice exhibited greater baseline preference for specific unfamiliar objects as well as more patterned sequences of sequential investigations of those items. These results suggest that the repetitive, stereotyped behavior patterns of BTBR mice are relatively pervasive and reflect both motor and cognitive mechanisms. Furthermore, other pre-clinical mouse models of ASDs may benefit from these more detailed analyses of stereotypic behavior.

Autism spectrum disorder (ASD) is the most commonly diagnosed neurodevelopmental disorder, with current estimates of more than 1% of affected children across nations. The patients form a highly heterogeneous group with only the behavioral phenotype in common. The genetic heterogeneity is reflected in a plethora of animal models representing multiple mutations found in families of affected children. Despite many years of scientific effort, for the majority of cases the genetic cause remains elusive. It is therefore crucial to include well-validated models of idiopathic autism in studies searching for potential therapeutic agents. One of these models is the BTBR T+Itpr3tf/J mouse. The current review summarizes data gathered in recent research on potential molecular mechanisms responsible for the autism-like behavioral phenotype of this strain.

Wild-trapped Rattus norvegicus show a consistent pattern of fear and defensive behavior to nonpainful stimuli such as an approaching experimenter, an anesthetized conspecific, or tactile stimulation of the back and vibrassae, as well as to painful stimuli. This reactivity to a range of stimuli, and the different behaviors by which such fear or defensiveness may be expressed, including flight, freezing, vocalization, the jump-attack, and specific biting patterns, make wild rats very appropriate subjects for the analysis of brain mechanisms underlying fear. Lesions of the mesencephalic central gray dramatically lowered these defensive reactions to both painful and nonpainful threat stimuli, reducing or eliminating each of the defensive reactions measured. The subjects showed no evidence of significant motor impairment or disturbance of primary sensory mechanisms. Because these experimental lesions involved considerable damage to the superior colliculi, a second study used wild rats with qamage only to the colliculi. These animals displayed some deficits in visually guided behavior and in reactivity to certain tactile stimuli, but most of their fear reactions were intact. These findings suggest that the mesencephalic central gray, traditionally regarded as involved in reactivity to pain, may be one component of a mechanism underlying fear and defensive behaviors to nonpainful as well as noxious stimuli.

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