Elsevier

Experimental Neurology

Volume 183, Issue 2, October 2003, Pages 600-609
Experimental Neurology

Regular article
Modification of hippocampal neurogenesis and neuroplasticity by social environments

https://doi.org/10.1016/S0014-4886(03)00248-6Get rights and content

Abstract

Synaptic plasticity and neurogenesis in the brain are affected by environmental stimuli. The present study was designed to investigate the effects of social environments on learning and memory, neurogenesis, and neuroplasticity. Twenty-two-day-old rats were housed in isolation or in groups for 4 or 8 weeks and injected intraperitoneally with bromodeoxyuridine to detect proliferation among progenitor cells. The animals were also tested for learning in a water maze and for hippocampal CA1 long-term potentiation in vivo and in vitro. The results show that the number of newborn neurons in the dentate gyrus and the learning in a water maze decreased significantly in rats reared in isolation for 4 or 8 weeks, as compared with grouped controls. Induction of long-term potentiation in the CA1 area of rat hippocampus in vivo and in vitro was also significantly reduced by isolation. Furthermore, the effects of isolation rearing on spatial learning, hippocampal neurogenesis, and long-term potentiation could be reversed by subsequent group rearing. These findings demonstrated that social environments can modify neurogenesis and synaptic plasticity in adult hippocampal regions, which is associated with alterations in spatial learning and memory.

Introduction

Events experienced in early life may contribute to the expression or exacerbation of a variety of physical and psychological disorders. Rearing animals in isolation is a relevant paradigm for studying early life stress and for understanding the genesis of certain neurological and psychiatric diseases Myhrer 1998, Whitaker-Azmitia et al 2000. The so-called isolation syndrome has been well characterized and consists of spontaneous and conditioned locomotor hyperactivity (Heidbreder et al., 2000), enhanced responses to novel environments, greater tendency toward preservation, deficits in prepulse inhibition, and altered response to the behavioral effects of drugs such as opioids and amphetamine-like psychostimulants Morutto and Phillips 1997, Smith et al 1997. Accumulating evidence demonstrates that social environments in early life significantly influence not only the organization of behavior but also the development of the brain. In particular, social isolation impairs memory processes but the mechanism for this effect is not known Myhrer 1998, Nilsson et al 1999.

Unlike cells in most tissues, which undergo generation and replacement throughout life, most neurons of the mammalian brain are generated entirely during early development, either before birth or shortly thereafter, and are not replaced if lost (Rakic, 1985). However, recent evidence has shown that in certain brain areas such as hippocampus, olfactory bulb, and neocortex, new neurons are also generated during adulthood Elizabeth and Charles 2002, Gould et al 1997, Gould et al 1999, Gould et al 1999, Gould et al 2001, Rakic 2002, Rocht et al 2002. The newly generated cells with neuronal features have been detected recently in the dentate gyrus of humans, in autopsy material of patients exposed to the thymidine analog 5-bromodeoxyuridine (BrdU) at advanced age (Elizabeth and Charles, 2002). The production and survival of these newborn neurons may contribute to neuroplasticity and a variety of hippocampus related functions, including learning and memory Snyder et al 2001, Kempermann et al 1997a, Van Praag et al 1999, Varty et al 1999.

Hippocampal neurogenesis is dependent on both genetic (Kempermann et al., 1997b) and environmental factors Bengzon et al 1997, Jones et al 1992, but the mechanisms underlying the effect of social interaction in early and adult life on hippocampal neurogenesis are largely unknown. Therefore, this study investigated the influence of early social isolation on neurogenesis and neuroplasticity in hippocampus and their association with the alterations in spatial learning by early social isolation. For this purpose we used a water maze task for spatial learning and determined hippocampal long-term potentiation (LTP), a model of synaptic plasticity thought to underlie memory and learning processes Bliss and Collingridge 1993, Malenka and Nicoll 1993.

Section snippets

Animals and housing conditions

Male Sprague–Dawley rats (Shanghai Center of Experimental Animals, Chinese Academy of Sciences) were used. Rats were reared at weaning under two different conditions: isolation rearing (one per cage) and group rearing (five per cage). Thus, in the first animal model, rats randomly received 4 weeks of isolation rearing (S4w) or group rearing (G4w) from Postnatal Days 22 to 49. In the second animal model, rats randomly received 8 weeks of isolation rearing (S4w/S4w), 8 weeks of group rearing

Effect of social isolation on spatial learning

The results show that rats housed individually for 4 weeks (S4w) demonstrated impaired performance on the spatial learning task as compared with those reared in groups for 4 weeks (G4w). As shown in Fig. 1, the isolated rats spent more time and swam greater distances to find and climb onto the hidden platform (for latency to find the platform, F (1, 15) = 13.51, P < 0.01, and for swimming distance, F (1, 15) = 9.54, P < 0.01), which is in agreement with earlier studies Pacteau et al 1989,

Discussion

Rats reared under conditions of isolation from weaning express a number of behavioral changes relative to their socially reared counterparts. For instance, isolated rats are hyperactive, exhibit deficits in prepulse inhibition of the startle response, and also demonstrate learning and memory impairments on certain tasks Jones et al 1992, Paulus et al 2000, Varty et al 1999. Some of these behavioral changes resemble clinical aspects of schizophrenia and Alzheimer’s disease. Thus, early isolation

Acknowledgements

We thank Dr. Y. Shaham for critical reading of the manuscript and helpful suggestions and Y. J. Lu for clerical work. This work was supported in part by grants from the National Natural Science Foundation of China (30230130, 39825110, 30000050, and 20021003), the Ministry of Science and Technology (G1999054003 and G1999053907), the National Foundation for Postdoctoral Research, the Ministry of Education, and Shanghai Municipal Commissions for Education and Science and Technology.

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