SHORT-TERM EXPOSURE TO AN ENRICHED ENVIRONMENT ENHANCES DENDRITIC BRANCHING BUT NOT BRAIN-DERIVED NEUROTROPHIC FACTOR EXPRESSION IN THE HIPPOCAMPUS OF RATS WITH VENTRAL SUBICULAR LESIONS B. BINDU, P. A. ALLADI, B. M. MANSOORALIKHAN, B. N. SRIKUMAR, T. R. RAJU AND B. M. KUTTY* Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, P.O. Box 2900, Hosur Road, Bangalore 560 029, India Abstract—Environmental enrichment promotes structural and behavioral plasticity in the adult brain. We have evalu- ated the efficacy of enriched environment on the dendritic morphology and brain-derived neurotrophic factor (BDNF) expression in the hippocampus of ventral subicular–lesioned rats. Bilateral ventral subicular lesion has significantly reduced the dendritic architecture and spine density of hippocampal pyramidal neurons. The lesioned rats exposed to enriched housing for 10 days showed a significant degree of morpho- logical plasticity in terms of enhanced dendritic branching and spine density. However, the BDNF expression in the hippocampus remained unchanged following subicular le- sion and following environmental enrichment. We suggest the participation of other neurotrophic factors in mediating the synaptic plasticity events following exposure to environ- mental enrichment in ventral subicular–lesioned rats. © 2006 IBRO. Published by Elsevier Ltd. All rights reserved. Key words: brain lesion, dendritic atrophy, neuronal plasticity. Environmental enrichment has been extensively used to demonstrate the behavioral and brain plasticity in response to experience (Rosenzweig et al., 1962; Greenough et al., 1973). Various studies have reported that adult rats exposed to a complex environment consisting of a combination of social stimulation and physical activity induce chemical and anatomical changes and enhanced behavioral perfor- mance (Connor and Diamond, 1982; Faherty et al., 2003; Fiala et al., 1978; Knafo et al., 2001; Rampon et al., 2000; Bennett et al., 1969; Diamond et al., 1964, 1966, 1975; Altman and Das, 1965). Additionally different types of en- richment may have different effects as reported by Bennett et al. (2006). They have observed an overall enhancement of spatial memory functions in aged mice when exposed continuously for a long period to enriched environment (EE) than providing daily enrichment. The neuroanatomi- cal changes are attributed to alterations in gene expres- sion linked to neuronal structure, synaptic plasticity and transmission (Rampon and Tsien, 2000). Changes in neu- rotrophins’ mRNA levels in the cortex and hippocampus may also play an important role in experience induced shaping of neuronal connection (Torasdotter et al., 1996). The neurotrophins like brain-derived neurotrophic factor (BDNF) and nerve growth factor play a major role in syn- aptic plasticity in the hippocampus and other brain regions such as somatosensory and visual cortex (McAllister et al., 1995, 1996). Experience-associated changes in brain morphology leading to functional recovery have been reported after brain injury (Kolb and Gibb, 1991; Kolb et al., 1998; Passineau et al., 2001). Rats subjected to environmental enrichment following transient global cerebral ischemia exhibited enhanced morphological and behavioral plastic- ity (Briones et al., 2000). Enriched rehabilitation following middle cerebral artery occlusion improved motor perfor- mances in staircase reaching and beam traversing tasks in ischemic rats. Enriched housing has in fact produced en- hanced dendritic complexity in the layer V pyramidal cells within undamaged motor cortex. Task specific rehabilita- tion augments neuronal plasticity in the affected region of the brain and thereby promotes functional outcome (Bier- naskie and Corbett, 2001). Similarly, studies have reported increased dendritic complexity in the undamaged sensori- motor cortex following exposure to EE in rats with cortical lesion and cerebral infarction (Jones and Schallert, 1994; Johansson, 1996). Young et al. (1999) have also reported the various plasticity evoking properties of environmental enrichment following brain insults. They have suggested that enriched housing helps to optimize the structural mor- phology in the intact brain. Gobbo and O’Mara (2005) found that EE enhances functional recovery after ischemia and they attributed the recovery to enhanced BDNF ex- pression following environmental enrichment. BNDF/ty- rosine kinase B signaling has been shown to mediate morphological plasticity in the hippocampal neurons (Tyler and Pozzo-Miller, 2001). Additionally this may act as an environmental stimuli to preserve some aspects of molec- ular machinery responsible for neuronal plasticity (Restivo et al., 2005). *Corresponding author. Tel: +91-80-26995170; fax: +91-80-2656- 2121 or +91-80-2656-4830. E-mail address: bindu@nimhans.kar.nic.in (B. M. Kutty). Abbreviations: BDNF, brain-derived neurotrophic factor; CA1, cornu ammonis 1; CA3, cornu ammonis 3; EE, enriched environment; FITC, fluorescein thiocyanate; NC, normal control; PBS, phosphate-buffered saline; PBSTx, phosphate-buffered saline with Triton X-100; TBS– Tween, 250 nM Tris–HCl, 0.9% NaCl and 0.1% Tween 20; VC, vehicle control; VSL, ventral subicular–lesioned; VSL+EE, ventral subicular– lesioned rats reared in enriched housing condition; VSL+SH, ventral subicular–lesioned rats reared in standard housing condition. Neuroscience 144 (2007) 412– 423 0306-4522/07$30.00+0.00 © 2006 IBRO. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.neuroscience.2006.09.057 412