Research reportDifferential environmental exposure alters NMDA but not AMPA receptor subunit expression in nucleus accumbens core and shell
Introduction
Environmentally enriched (EE) rats show neural and behavioral differences relative to littermates placed in less stimulating socially isolated (SI) conditions (for review, see [52]). This manipulation, typically referred to as differential environmental experience, was one of the first procedures used to examine experience-dependent plasticity in the central nervous system. Many early investigations using this technique focused on cortical plasticity, demonstrating a variety of experience-related cortical effects including enhanced gliogenesis, synaptogenesis, and increased cortical weight and size in EE relative to SI animals [1], [56], [65] and parallel group learning differences [57]. Generally, learning is presumed to improve in EE relative to SI animals [52], although many studies report conflicting results [7], [16], [24], [31], [40], [48], [59], [60]. More recent work reveals emotional [41] and motivational [54] effects of differential environmental experience. Consistent with a motivational change, EE rats show reduced reward-seeking behavior [5], [26], [63] and altered structure [19] and function [4], [25] of the nucleus accumbens (NAcc), a forebrain nucleus known for its involvement in natural and drug reinforcement [14], [37].
The NAcc integrates dopaminergic and glutamatergic limbic-related inputs with the extrapyramidal motor system via projections to downstream basal ganglia output structures [49], suggesting that emotional–motivational influences gain access to behavior through this brain region [43]. Although alterations in dopaminergic transmission and metabolism have been observed in the NAcc of EE rats relative to SI and socially housed rats [4], [11], it is unknown what effect differential environmental experience has on glutamatergic transmission. Given the established function of glutamate in neural plasticity [10] and its interaction with dopamine in motivational and associative processing in this brain region [37], we assessed the effect of EE exposure on glutamate receptor subunit expression in the core and shell subregions of the NAcc. We focused on NR1 subunits because all N-methyl-d-aspartate (NMDA) receptors require at least one of these proteins for channel activity [42], [44]. In addition, NR1 subunits are involved in the regulation of dendritic architecture in development [32]. We also assessed GluR-1 subunits of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors because they are abundant in the NAcc [8], [15] and, like NR1 subunits, are involved in regulating dendritic morphology during development [33].
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Animal care
Male, Sprague–Dawley pups (n = 12) bred in our colony from stock rats (Harlan Industries, Indianapolis, IN) were cross-fostered from two litters on postnatal day (p) 2. After weaning at p28, these rats were randomly assigned to either the EE (n = 6) or SI (n = 6) condition, respectively. SI animals (20 cm × 23 cm × 18 cm) were housed individually and EE rats (89 cm × 69 cm × 39 cm) were housed together in stainless-steel wire mesh cages. The EE cage contained toys, tunnels, and ladders, which
Stereological information
Mean (±SEM) optical density of the white matter samples was 184.94 ± 4.62 for NR1-stained sections and 203.75 ± 7.12 for GluR1-stained sections. The mean number of objects counted per frame was 27.24 ± 1.25 and 27.39 ± 1.31 for NR1-positive neurons in core and shell, respectively, and 18.79 ± 0.88 and 19.05 ± 0.99 for GluR1-positive neurons. For NR1-positive neurons, the total number of objects counted across the five frames averaged 129 ± 9.7 and 124 ± 8.3 in core and shell, respectively; for
Discussion
Overall, our results indicate that exposure to different housing environments alters expression of NR1 but not GluR1 subunits in neurons in both NAcc core and shell. Specifically, the density of intensely stained NR1-positive neurons in both core and shell was lower in EE relative to SI rats, while the density of lightly stained NR1-positive neurons was higher in both NAcc subregions of EE relative to SI rats. GluR1 immunohistochemistry revealed no such differences. Importantly, neither overall
Acknowledgments
This research was supported by U.S. Public Health Service grants from the National Institute on Drug Abuse (DA 02451, DA 12964, DA05312). We also thank Faye Caylor for administrative support and Paul Langley for construction of the enriched environment housing.
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