Behavioural Brain Research 214 (2010) 91–101 Contents lists available at ScienceDirect Behavioural Brain Research journal homepage: www.elsevier.com/locate/bbr Research report Learning-induced alterations in prefrontal cortical dendritic morphology Wendy L. Comeau ∗ , Robert J. McDonald, Bryan E. Kolb Canadian Center for Behavioral Neuroscience, University of Lethbridge, Lethbridge, T1K 3M4, Canada article info Article history: Received 24 February 2010 Received in revised form 18 April 2010 Accepted 20 April 2010 Available online 28 April 2010 Keywords: Rat Learning Neuroplasticity Medial prefrontal cortex Orbitofrontal cortex abstract The influences of complex housing, T-maze, and Grice box training on dendritic morphology of the pre- frontal cortex (PFC) and primary somatosensory (Par 1) were investigated in the rat. Golgi–Cox analyses demonstrated that all learning paradigms produced alterations in PFC connectivity, albeit differently. Fur- thermore, the effects of experience on dendritic morphology varied by region, hemisphere, and lamina and often resulted in opposing changes within each. For example, complex housing produced a time- dependent decrease in the dendritic fields of layer (L) V neurons in region 3 of the cingulate cortex (Cg3) in the medial PFC (mPFC) neurons and increases in LIII of the dorsal agranular insular (AID) region of the orbitofrontal cortex. In contrast, T-maze training produced increases in Cg3 LV and decreases in AID LIII spine density. Of interest, the influence of experience was not reflected equally between hemispheres. For example, T-maze training produced an increase in Cg3 LV and AID LIII branch order and length in the right hemisphere, and an increase in Cg3 LIII branch order in the left hemisphere. Additionally, correlation analysis of task performance and dendritic morphology indicated an opposing influence of experience within the different laminae of the Cg3. For example, whereas, performance was negatively correlated with Cg3 LV dendritic branch order/length, there was a positive correlation with Cg3 LIII den- drites. Complex housing induced changes in the Par 1were also time -dependent but were only apparent after a prolonged period of exposure. In addition to demonstrating learning-specific modifications in dendritic connectivity within the PFC, the results illustrate varying patterns of change that likely reflect task-dependent requirements on the PFC. © 2010 Elsevier B.V. All rights reserved. 1. Introduction Complex housing is one of the most widely studied models of experience-dependent structural plasticity; consistently pro- ducing robust changes in neuronal morphology in the visual and somatosensory cortex in the developing and the mature brain [1–4], and alterations in subcortical structures such as the nucleus accumbens (NAc) in adults [5,6], that coincide with alterations in performance as well [7]. Of importance, these studies illustrate a direct relationship between structure and function. Experience- related alterations in structural morphology are not restricted to complex environments, however. Training-induced changes have also been found in the occipital cortex of animals trained in visual spatial tasks [8], the motor cortex following reach training [9], the piriform (olfactory) cortex with odor discrimination training [10], as well as in the cerebellar cortex following motor learning but not exercise [11]. Based on these and subsequent studies it would seem reasonable to expect to find learning-related changes in the pre- ∗ Corresponding author at: University of British Columbia, Department of Cellular & Physiological Sciences, Life Sciences Center, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada. Tel.: +1 604 822 4554; fax: +1 604 822 2316. E-mail address: comeauwe@interchange.ubc.ca (W.L. Comeau). frontal cortex (PFC) as well. Yet, few studies have included the PFC when investigating changes in neuronal morphology related to spe- cific forms of learning. This is somewhat surprising given the role that the PFC plays in learning and executive functions, in addition to its extensive capacity for reorganization in response to injury (see Kolb and Gibb [12] and psychostimulant use [13,14]). Owing to the limited conditions in which changes in the PFC were investigated, in the current set of studies we sought to test the hypothesis that observable experience-related structural changes may be time and task specific. To our knowledge, the only three published studies that have examined learning-related structural changes in pyramidal neu- rons of the medial prefrontal cortical (mPFC) have reported variable changes. For example, Kolb et al. [5] reported no changes in den- dritic arborization of layer V Cg3 neurons in rats following complex housing or maze training [15], but the researchers did report learning-related changes in layer (L) III Cg3 neurons in the lat- ter experience. In contrast to the Kolb findings [5], Kozorovitskiy et al. [16] reported altered dendritic arborization in PFC neurons in non-human primates housed in complex environments. Aside from species, a number of other differences in methodology may account for the discrepancy in results. For example, whereas the Kolb complex housing study examined LV only, the Kozorovitskiy study focused on LIII neurons in the PFC. Thus it may be that layer 0166-4328/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2010.04.033