TRIGEMINOTHALAMIC BARRELETTE NEURONS: NATURAL STRUCTURAL SIDE ASYMMETRIES AND SENSORY INPUT-DEPENDENT PLASTICITY IN ADULT RATS P. NEGREDO, a,b Y. B. MARTIN, a A. LAGARES, c J. CASTRO, d J. A. VILLACORTA e AND C. AVENDAÑO a * a Department of Anatomy, Histology, and Neuroscience, Medical School, Autonoma University of Madrid, c/ Arzobispo Morcillo 2, 28029 Madrid, Spain b Institute ‘Teófilo Hernando’, Medical School, Autonoma University of Madrid, c/ Arzobispo Morcillo 2, 28029 Madrid, Spain c Department of Neurosurgery, Hospital 12 de Octubre, Complutense University of Madrid, Avda. de Córdoba s/n., 28041 Madrid, Spain d Brain and Cognitive Science Department, MIT, 43 Vassar Street, Cam- bridge, MA 02139, USA e Pluridisciplinary Institute, Complutense University of Madrid, 28040 Ma- drid, Spain Abstract—In the rodent trigeminal principal nucleus (Pr5) the barrelette thalamic-projecting neurons relay information from individual whiskers to corresponding contralateral thalamic barreloids. Here we investigated the presence of lateral asymmetries in the dendritic trees of these neurons, and the morphometric changes resulting from input-dependent plas- ticity in young adult rats. After retrograde labeling with dex- tran amines from the thalamus, neurons were digitally recon- structed with Neurolucida™, and metrically and topologically analyzed with NeuroExplorer™. The most unexpected and remarkable result was the observation of side-to-side asym- metries in the barrelette neurons of control rats. These asym- metries more significantly involved the number of low-grade trees and the total dendritic length, which were greater on the left side. Chronic global input loss resulting from infraorbital nerve (IoN) transection, or loss of active touch resulting from whisker clipping in the right neutralized, or even reversed, the observed lateral differences. While results after IoN tran- section have to be interpreted in the context of partial neuron death in this model, profound bilateral changes were found after haptic loss, which is achieved without inflicting any nerve damage. After whisker trimming, neurons on the left side closely resembled neurons on the right in controls, the natural dendritic length asymmetry being reversed mainly by a shortening of the left trees and a more moderate elongation of the right trees. These results demonstrate that dendritic morphometry is both side- and input-dependent, and that unilateral manipulation of the sensory periphery leads to bilateral morphometric changes in second order neurons of the whisker-barrel system. The presence of anatomical asym- metries in neural structures involved in early stages of so- matosensory processing could help explain the expression of sensory input-dependent behavioral asymmetries. © 2009 IBRO. Published by Elsevier Ltd. All rights reserved. Key words: trigeminal nuclei, experience-dependent plasticity, lateralization, dendrites, brain asymmetries, deafferentation. Mature neurons respond to relevant alterations of their afferent input with a cohort of molecular, biophysical, and anatomical changes, which have provided an active area of research throughout the last few decades. Structural plasticity studies have mainly focused on synapses, which change in number and/or structure in all regions studied under a variety of input alterations. Such changes have been reported for example in the motor cortex, following sustained increases in afferent activity after motor learning (Federmeier et al., 2002; Kleim et al., 1996); in the barrel cortex after artificial repetitive whisker stimulation (Knott et al., 2002); in the hippocampus following hippocampus- dependent associative learning (Geinisman et al., 2001); in the somatosensory cortex after LTP induction (Connor et al., 2006); and in supragranular layers of the barrel cortex after chronic whisker clipping (Machin et al., 2006). Fol- lowing synapses themselves, dendritic spines are the structures that display the most remarkable activity-depen- dent plasticity, and are the ones that have been most thoroughly investigated (for review, see Alvarez and Sa- batini, 2007; Yuste and Bonhoeffer, 2001). While far from neglected, mature dendritic trees have attracted much less attention as targets for activity- or experience-dependent plasticity in adult subjects. This can be justified by the lack of dendritic restructuring in cortical pyramidal cells during adult life in mice (Trachtenberg et al., 2002), and the remarkable dendritic stability displayed by olfactory bulb mitral and tufted cell of mice under changing odorant con- ditions (Mizrahi and Katz, 2003), and by giant neurons of a snail under sustained global decrease of sensory input (Chase and Tidd, 1991). Nevertheless, structural plasticity is evident in dendritic trees of many neuron types exposed to direct partial deafferentations (Bury and Jones, 2002; Mantyh et al., 1995; Sugimoto and Gobel, 1984; Takacs and Hamori, 1990), as well as in specific neuron types sensitive to hormones that exhibit physiological fluctua- tions (see Cooke and Woolley, 2005, for review). Less dramatic, but nonetheless important in order to document the dependence of dendritic trees on altered patterns of input arising from distant sources, are the mod- ifications found in cortical neurons after prolonged expo- sures to altered sensory inputs. This was first reported after exposing post-weaning rats to enriched environ- *Corresponding author. Tel: +34-91-497-5335; fax: +34-91-497-5338. E-mail address: carlos.avendano@uam.es (C. Avendaño). Abbreviations: BDA, biotinylated dextran amine; C, control (group); CyO, cytochrome oxidase; Io, infraorbital nerve transection (group); IoN, infraorbital nerve; PB, phosphate buffer; Pr5, principal trigeminal nucleus; T, whisker trimming (group); VPm, ventral postero–medial thalamic nucleus. Neuroscience 163 (2009) 1242–1254 0306-4522/09 $ - see front matter © 2009 IBRO. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.neuroscience.2009.07.065 1242