Developmental Brain Research 130 (2001) 1–7 www.elsevier.com / locate / bres Research report Neonatal exposure to a novel environment enhances the effects of corticosterone on neuronal excitability and plasticity in adult hippocampus a,d b b a,b,c, * Bende Zou , Golijeh Golarai , John A. Connor , Akaysha C. Tang a Department of Psychology, Logan Hall, Room 162, The University of New Mexico, Albuquerque, NM 87131, USA b Department of Neurosciences, The University of New Mexico, Albuquerque, NM 87131, USA c Department of Computer Science, The University of New Mexico, Albuquerque, NM 87131, USA d National Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, People’ s Republic of China Accepted 3 April 2001 Abstract Electrophysiological studies have shown that activation of glucocorticoids receptors (GRs) influences neuronal excitability and activity dependent synaptic plasticity. In developmental studies, early life stimulation such as neonatal handling results in an up-regulation of glucocorticoid-receptor (GR) binding in the hippocampus that persists into adulthood. It is, therefore, hypothesized that early environment-induced changes in receptor sensitivity to corticosterone (CORT) might have functional effects on adult neuronal excitability and synaptic plasticity. To test this hypothesis, we exposed rats daily from post-natal days 1–21 to a non-home environment for 3 min. When the animals became adults, we studied the effects of glucocorticoid hormone corticosterone (CORT) on population spike (PS) amplitude and long-term potentiation of population spikes (PS-LTP) in vitro in the hippocampal CA1 region following activation of the Schaffer collateral fibers. Bath application of CORT reduced PS amplitude and subsequent induction of PS-LTP. This inhibitory effect of CORT was significantly greater in the slices from the novelty exposed rats (Novel) than the control rats that remained in their home cage (Home). Inhibition of population spike amplitude during CORT perfusion was 28.065.3% of baseline in Novel slices, and 9.164.4% in Home slices. CORT pre-exposure (20 min) also inhibited the subsequent induction of PS-LTP in Novel slices by 57.7617.7% and by 7.5612.1% in Home slices. These results provide electrophysiological evidence that neonatal novelty exposure results in functional increases in receptor sensitivity to CORT that enhances the inhibitory effects of CORT on field CA1 neuronal excitability and plasticity.  2001 Elsevier Science B.V. All rights reserved. Theme: Development and regeneration Topic: Hormones and development Keywords: Corticosterone; Novelty; Population spike; CA1; Hippocampus; LTP 1. Introduction regulation of hippocampal glucocorticoid receptor (GR) binding, which mediates the negative feedback control of Postnatal environmental manipulations can result in CORT release [23,19,22,21,39]. These handled animals long-lasting changes within the hypothalamic–pituitary– also show less age-related cognitive decline than controls adrenal (HPA) axis and in the negative feedback control of [23], measured by performance in the Morris water maze the HPA axis [38,23,25,42,24,2]. Handling rat pups during task [27]. Although it is well known that CORT plays an infancy has been shown to result in long-lasting up- important role in modulating learning and memory [17,16,14,44,7] and that behavioral stress, exogenous application of corticosterone (CORT), and its agonists / *Corresponding author. Tel.: 11-505-277-4025; fax: 11-505-277- antagonists can all influence hippocampal dependent learn- 4946. ing [6,3,28,5,8,29–31,26], the cellular mechanisms con- E-mail addresses: akaysha@unm.edu (A.C. Tang), http: / / kongzi.un- m.edu (A.C. Tang). necting receptor up-regulation to enhanced hippocampal 0165-3806 / 01 / $ – see front matter  2001 Elsevier Science B.V. All rights reserved. PII: S0165-3806(01)00173-0