EARLY EXPERIENCE AND LEARNING

The brain of the developing organism is a unique and dynamic system. During the prenatal and postnatal periods the brain differs dramatically from that of the adult. For example, it contains more synapses early in development than it does at any other stage in life (Purves and Lichtman, 1980). Receptors for a number of neuropeptides (e.g., oxytocin) are found in higher concentrations early in development than later in life (Shapiro and Insel, 1989). In certain brain areas (e.g., the suprachiasmatic nucleus of the hypothalamus), glucocorticoid receptors are found in high concentrations only during early ontogeny (Van Eekelen et al., 1987). These are but a few examples that attest to the differences in the brain during development. For the most part, scientists have not determined the functional significance of these neuronal features of the newborn brain.

One of the critical aspects of the developing brain is its plasticity. Both physiological and environmental stimuli have been shown to profoundly, and often permanently, influence the functional capacities of the organism (Levine and Mullins, 1966). Neonatal disturbance of the normal hormonal milieu leads to some of the best-known cases of permanent alterations of function induced by early manipulations of physiological events. Neonatal exposure to heterotypical gonadal hormones, for example, results in a permanently altered reproductive physiology and behavior. Both over-and underexposure to thyroid hormone during early development cause changes in the brain that produce learning disabilities.

The purpose of this entry is to illustrate the effects of alterations in early environments on learning capacity in the adult organism. Several areas of investigation have demonstrated the importance of early experience for later behavior, using a number of different models to examine this issue. Thus, deprivation of visual experience early in development has been shown to markedly affect adult vision; this also affects the animal's behavior (Hyvarinen and Hyvarinen, 1979). There is an extensive research on the effects of "enriched environments" on subsequent learning ability (Rosenzweig, 1984). This entry examines the role of early handling as a model of infantile stimulation on learning in the adult.

In 1956 S. Levine and colleagues reported that neonatal manipulations have profound effects on later behavior. In essence, their study showed that neonatal handling (i.e., removing rat pups from their mother for a few minutes and returning them to their mother), or electric shock during the same period, markedly improved the animals' capacity to learn a conditioned avoidance response when tested as adults. This procedure involves placing the animal in a two-compartment chamber. Both sides of the chamber contain grid floors that can be electrified. The animal is presented with a signal, the conditioned stimulus, which is followed after a brief time by an electric shock. The animal is required to cross from the electrified side of the chamber to the safe side. If it crosses within the interval between the onset of the signal and the onset of shock, it avoids the shock (conditioned avoidance). However, if the animal fails to cross during this interval and the shock is delivered, this response is considered an escape response.

Researchers conducted a number of studies following their initial observations that demonstrated these marked differences between handled and non-handled pups. In order to verify whether the effects of early handling were age-dependent, early-handled pups were compared with nonhandled pups and with animals that were handled after weaning. Pups manipulated as infants were found to show avoidance learning superior to that of nonhandled pups. Post-weaning-handled animals were more similar to non-handled rats.

Although experiments showed that early handling improved avoidance learning, the underlying causes of this improvement remained to be determined. One possible explanation for these findings is that emotional reactivity was modified as a function of these early experiences. The more efficient avoidance learning may therefore be a consequence of reduced arousal levels. Increasing the shock levels during avoidance conditioning results in an inverted U-shaped function with regard to acquisition of the conditioned avoidance response. Thus, acquisition is improved by very low levels of shock but impaired by very high levels.

There are numerous reports that early handling reduces emotional reactivity (Whimbey and Denenberg, 1967). This reduced reactivity is demonstrable using both behavioral and physiological indices. Activity levels and defecation in the open field differ between handled and nonhandled subjects. Handled animals explore more actively (i.e., show less freezing), defecate less in the open field, are less neophobic (Weinberg, Smotherman, and Levine, 1978), and are less reactive to human handling as adults (Ader, 1965). One of the more sensitive physiological indices of arousal is the activation of the hypothalamicpituitary-adrenal (HPA) system (Hennessy and Levine, 1978). Following stress, nonhandled animals show plasma corticosterone (the primary glucocorticoid secreted by the rodent) elevations that are both larger and more persistent than those found in animals handled during infancy (Levine et al., 1967).

These differences in emotionality are consistently found using a variety of different testing paradigms. However, the effects of early handling on avoidance conditioning appear to vary when the parameters are different from those used in the original studies. Both R. Ader (1965) and J. Weinberg and S. Levine (1977) failed to find differences in conditioned avoidance response, although differences in emotional reactivity were clearly present. The question of whether early handling influences associative learning therefore still remained unanswered.

In order to address the issue of the effects of early handling on learning, V. H. Denenberg and J. R. C. Morton (1962) studied the effect of early handling on the ability of rats to learn tasks that did not involve noxious stimuli. These investigators examined the interaction between early handling and environmental enrichment on the ability of adult rats to solve a Hebb-Williams maze. After weaning handled and nonhandled rats were reared in a neutral, restricted, or enriched environment. The animals were then required to solve a sequence of twelve test problems. The results indicated that the animals' ability to learn the maze was affected by the postweaning, but not by the pre-weaning, manipulation. Thus, rats reared in an enriched environment made significantly fewer errors than those reared in neutral or restricted environments. Based on these results, it was concluded that pre-weaning handling affected emotional processes but not learning ability.

In 1972 R. Wong attempted to clarify the issue of whether early handling directly affects associative learning or whether the improvement in learning is due mainly to differences in emotional reactivity. An experiment was conducted that presumably could discriminate these two processes. Thus, subjects were trained to reach a criterion of stable performance on a positive reinforcement task (food) and then punished with an aversive stimulus (shock) for making the reinforced response. Comparisons could then be made in terms of the degree of response suppression following the presentation of the aversive event; and the rate of recovery after removal of the aversive stimulus. Wong argued that if handled animals showed greater response suppression and a slower recovery than nonhandled animals, this would indicate a direct effect of handling on learning. If the contrary occurred, it could be assumed that the primary influence on the behavior was attributable to differences in emotionality. Animals were trained to alternate goal boxes in a T-maze to obtain food. Once the criterion had been reached, they were given a shock in the goal box where they had obtained positive reinforcement (S+ box). Testing began one day after the punished trial. The animals were placed in the maze and received food only in the S+ box. During the acquisition phase the handled group made more correct responses (alternations) than the nonhandled group, indicating superior learning on a positive reinforcement task. Following the shock exposure handled rats made fewer choices to the food reward box (S+) than nonhandled animals, suggesting that handled animals had superior associative learning.

Decades later A. Tang (2001) investigated the role of exposure to novelty on hippocampal dependent learning. Neonatal rats were exposed for three minutes daily to a nonhome environment and compared with littermate controls that remained in the home cage for the period with the mother removed. The novelty exposed rats showed more rapid acquisition as juveniles and greater retention in adulthood in a spatial learning task. Further, these animals also showed greater retention in an odor discrimination task.

In many of the studies described above, learning was investigated using behavioral situations in which an aversive motivational component was present, making it difficult to dismiss entirely the effects of emotional reactivity on learning. Latent inhibition, a behavioral paradigm that avoids some of these problems, has been used to examine the relationship between handling and learning. This paradigm was described in the context of classical conditioning. Ivan Pavlov was the first to demonstrate that repeated exposure to a conditioned stimulus (CS), prior to pairing this stimulus with an unconditioned stimulus (UCS), impairs the rate of conditioning that subsequently occurs (Pavlov, 1927). Thus, repeated exposure to a stimulus that is not followed by meaningful consequences renders this stimulus ineffective for subsequent learning.

I. Weiner, Schnabel, Lubor, and Feldon (1985) employed the latent inhibition paradigm to study the question of early handling and learning. The experiment was conducted in two phases. During the first phase (preexposure) members of one group were placed in a shuttle box and presented with sixty five-second tones. Members of the second group were placed in the shuttle box for an equivalent time without exposure to the tones. In the second phase the animals were presented with one hundred tone (CS) and shock (UCS) pairings and the number of conditioned avoidance responses was recorded. The results showed that nonpreexposed handled animals exhibited better avoidance learning than nonhandled rats, thus replicating earlier findings. However, pre-exposed handled animals performed more poorly than non-pre-exposed handled rats. The findings were to some extent sex-dependent: Whereas preexposed handled males and females and preexposed nonhandled females exhibited the latent inhibition (i.e., performed more poorly than nonpreexposed animals), the nonhandled males did not show any effect of preexposure on the conditioned avoidance response.

In a further study, latent inhibition was investigated using a conditioned emotional response (CER) to test the influence of early handling (Weiner, Feldon, and Ziv-Harris,1987). The CER procedure was conducted in three phases: 1. pre-exposure; 2. acquisition, in which the pre-exposed tone was paired with shock; and 3. testing, during which latent inhibition was indexed by the animals' suppression of licking during tone presentation. As in the previous experiment, latent inhibition was observed in the handled males and females and in nonhandled females, but not in the nonhandled males. Based on both of these studies, the conclusion was that early handling exerts a beneficial influence on learning capacity in the adult animal.

Only a very limited literature has attempted to examine the neural substrates of the early handling phenomenon. Michael Meaney and his colleagues (1988) studied the long-term influence of early handling on the neuroendocrine regulation of the HPA system. These researchers reported a long-term down regulation of glucocorticoid receptors (GR) in the hippocampus of nonhandled, but not of handled, aged animals. They further reported that spatial learning, a hippocampus-dependent process, is significantly improved in aged animals that had undergone early handling. However, the aged nonhandled animals appeared to have suffered hippocampal cell loss. The differences in spatial learning may thus be due to the prevention of this cell loss by early handling. However, given the results presented by Tang, it would appear that the influence of early experiences on hippocampal dependent learning is evident throughout the life span. These studies do demonstrate the long-term consequences of early handling for at least one aspect of neural regulation. Although the implications of this down regulation of GRs for learning have not been extensively investigated, there is some evidence that administering specific GR antagonists interferes with the acquisition of a spatial learning task (Oitzl, and de Kloet, 1992). Other aspects of the HPA system also seem to be involved in learning and memory (van Wimersma Greidanus, 1982).

Conclusion

There are many examples in the literature of long-term consequences of manipulations during infancy that affect learning and memory. However, most of these studies have utilized toxic agents resulting in permanent and irreversible morphological and physiological changes in the central nervous system that are later reflected as impairments in the adult organism's ability to learn (Grimm, 1987). Environmental enrichment and early handling constitute examples of subtle environmental manipulations that cause permanent alterations in adult function that facilitate rather than impair adult learning abilities.

See also:CHILDREN, DEVELOPMENT OF MEMORY IN;EMOTION, MOOD, AND MEMORY

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SeymourLevine

DeborahSuchecki