Sensorimotor developmental factors influencing the performance of laboratory rodents on learning and memory

Abstract

Behavioral studies in animal models have advanced our knowledge of brain function and the neural mechanisms of human diseases. Commonly used laboratory rodents, such as mice and rats, provide a useful tool for studying the behaviors and mechanisms associated with learning and memory processes which are cooperatively regulated by multiple underlying factors, including sensory and motor performance and emotional/defense innate components. Each of these factors shows unique ontogeny and governs the sustainment of behavioral performance in learning tasks, and thus, understanding the integrative processes of behavioral development are crucial in the accurate interpretation of the functional meaning of learning and memory behaviors expressed in commonly employed behavioral test paradigms. In this review, we will summarize the major findings in the developmental processes of rodent behavior on the basis of the emergence of fundamental components for sustaining learning and memory behaviors. Briefly, most sensory modalities (except for vision) and motor abilities are functional at the juvenile stage, in which several defensive components, including active and passive defensive strategies and risk assessment behavior, emerge. Sex differences are detectable from the juvenile stage through adulthood and are considerable factors that influence behavioral tests. The test paradigms addressed in this review include associative learning (with an emphasis on fear conditioning), spatial learning, and recognition. This basic background information will aid in accurately performing behavioral studies in laboratory rodents and will therefore contribute to reducing inappropriate interpretations of behavioral data and further advance research on learning and memory in rodent models.

Keywords: Behavioral tests; Development; Juvenile; Neonatal; Pubertal; Rodents.

Figure 1.

Neonatal sensorimotor development in laboratory rodents. The pictures of C57BL/6 mice represent physical appearance development from P-0 (at birth) to P-15. Motor control indicates the development of motor control from partial, primitive movement to whole-body integrated movement. Emergence of behaviors observed through the neonatal period includes; huddling (temperature control) and suckling (milk), righting reflex (posture control), ultrasound vocalization (distress call), walking, startle response (defense), behavioral inhibition (defense), running, and jumping. Sensory development includes visual, auditory, tactile, and olfactory functions.

Figure 2.

Development of sensorimotor, defense, and social behaviors and specific learning tasks including the fear conditioning (associative learning), spatial learning, and recognition, in laboratory rodents; mice and rats. Sensorimotor. Most sensory modalities are functional accompanied by the emergence of motor control before the weaning period (around postnatal day 21). Defense. Behavioral inhibition is observed from around P- 12, when rodent pups begin walking. After the weaning period, several defensive behaviors including exploratory behavior, stretch-attend postures, and defensive burying emerge and reach the highest in the late juvenile stage. Social. During the neonatal period, the primary relationship includes mother-offspring interaction is associated with separation-induced distress call by pups. After the weaning period, rodent pups engage playful interaction with siblings and decrease it afterward. Following the pubertal stage, sexually-matured rodents develop territorial behavior that is relevant to dominance-subordinate relationships and sexual behaviors. Associative learning using a fear conditioning paradigm is observable in the neonatal stage, the emergence of which alters with sensory cues utilized, and from P-17 with artificial auditory cues in the regular conditioning chamber and from P-23 with spatial, contextual cues. Conditioned fear response including tolerance of extinction is enhanced during the late-juvenile to pre-pubertal stage. Spatial learning that is represented by Morris water maze performance emerges around P-17 when intramaze cues are available, and P-23 when exteriormaze landmarks are presented. Impairment in reversal learning in the Morris water maze was demonstrated in late-juvenile mice. Recognition memory performed in a novel object recognition test emerges during P-17 when the interval was very short (5 min), and during before P-22 when the interval was short (e.g., <1 h), and then long-term recognition memory (>24 h) is documented in the mid-juvenile stage.

Figure 3.

Considerable factors for examining the fear conditioning in mice. Functional sensory modalities are required for detecting conditioned stimulus (CS). Tactile (pain) sense is relevant to reception of unconditioned stimulus (US). Development of behavioral patterns including freezing (i.e., passive defense) and extinction has been reported.

Figure 4.

Considerable factors for examining spatial learning in mice. Visual detection of intra- and extra-landmarks surrounding the apparatus is required. Functional tactile sense is prerequisite for sensing a (visually) hidden platform in the Morris water maze. Intact locomotive (swimming) abilities are required. Developmental fluctuation in exploratory behavior and response to the reversal learning has been reported.

Figure 5.

Considerable factors for investigating recognition memory in mice. Detection and discrimination of the objects (or social or unsocial cues) via available sensory modalities (e.g., visual, tactile, or olfactory) are necessary. Some developmental fluctuation of investigatory (locomotor) behavior is known.