Immune Proteins in Brain Development and Synaptic Plasticity Lisa M. Boulanger  Neuron  Volume 64, Issue 1, Pages 93-109 (October 2009) DOI: 10.1016/j.neuron.2009.09.001 Copyright © 2009 Elsevier Inc. Terms and Conditions

Figure 1 Expression of mRNA Encoding MHCI and Immunoreceptors for MHCI in Healthy Adult Rodent Brain S35 labeling using antisense probes against specific MHCI mRNAs or mRNAs encoding particular MHCI immunoreceptors in sections of adult mouse brain (in B–D, light areas indicate silver grains). (A) Pseudocolored in situ hybridization showing mRNA encoding three different MHCI genes in three overlayed serial coronal sections of adult mouse brain. Red, H2-D; blue, T22; green, Qa-1. Reprinted with permission from Boulanger et al. (2001). (B) Paired immunoglobulin-like receptor B (PIRB) mRNA detected in a sagittal section. Scale, 1 mm. Reprinted with permission from Syken et al. (2006), copyright 2006 National Academy of Sciences, USA. (C) Killer cell immunoglobulin-like receptor-like gene (KIRL) mRNA detected in a sagittal section. Olfactory bulb (OB), hippocampal dentate gyrus (DG), and cerebellum (CB). Modified with permission from Bryceson et al. (2005). (D) Unrecombined T cell receptor beta subunit (TCRβ) mRNA detected in a sagittal section. Reprinted with permission from Syken and Shatz (2003). Neuron 2009 64, 93-109DOI: (10.1016/j.neuron.2009.09.001) Copyright © 2009 Elsevier Inc. Terms and Conditions

Figure 2 Dscam Encodes Diverse Proteins that Display Homophilic Binding and Mediate Normal Self-Avoidance between Sister Neurites or between Neurites of a Single Cell Type (A) Constant and variable regions in the Dscam gene in Drosophila. Differential splicing of exons 4, 6, 9, and 17 can produce up to 38,016 distinct Dscam mRNA isoforms. Modified with permission from Wojtowicz et al. (2004). (B) Schematic illustration of the molecular basis of Dscam homophilic interactions. In most cases, matching at all three variable domains is required for binding. Modified with permission from Sawaya et al. (2008). (C) Homophilic binding between Dscam isoforms that vary only at the IgG3 domain. Ig3 domains are arranged according to their sequence relatedness, as shown in the dendrograms, and binding is indicated as fold over background by a color scale and the number in each block. Red diagonal line indicates that binding is preferentially homophilic. Reprinted with permission from Wojtowicz et al. (2007). (D) Loss of Dscam in single Drosophila neurons causes extensive dendritic self-crossing of sister branches of the same cell, resulting in tangled and disorganized dendritic fields in dendritic arborization (da) class I neurons. This phenotype is rescued by expression of either of two specific Dscam isoforms (1.30.30.1 or 11.31.25.1) in single neurons in an otherwise Dscam null background. Scale, 10 μm. Modified with permission from Hughes et al. (2007). (E) Whole adult (6–8 week) wild-type (WT, left) or Dscam−/− (right) mouse retinas stained with anti-TH. Dopaminergic amacrine cell neurites arborize evenly, while in mice lacking DSCAM, amacrine cell neurites are bundled in thick fascicles. Modified with permission from Fuerst et al. (2008). Neuron 2009 64, 93-109DOI: (10.1016/j.neuron.2009.09.001) Copyright © 2009 Elsevier Inc. Terms and Conditions

Figure 3 Activity-Dependent Synaptic Plasticity in Two Regions of the Adult Mammalian CNS Requires Normal Expression of MHCI (A) MHCI protein (red) is expressed in dendrites and colocalizes with PSD-95 (green) in hippocampal neurons in vitro. Scale bar, 10 μm. Modified with permission from Goddard et al. (2007), copyright 2007 National Academy of Sciences, USA. MHCI mRNA is also seen in CA1 pyramidal cells (Figure 1A). (B) Hippocampal frequency-dependent synaptic plasticity is shifted in favor of potentiation in MHCI-deficient (β2 m−/−TAP1−/−) or CD3ζ-deficient mouse hippocampal slices. Reprinted with permission from Huh et al. (2000). (C) MHCI protein is expressed in Purkinje cell dendrites and throughout the molecular layer. Scale bar, 20 μm. (D) The threshold for pairing-induced LTD at parallel fiber-Purkinje cell synapses is reduced in MHCI-deficient mice lacking the classical MHCI genes Kb and Db (“KO”). (C) and (D) modified with permission from McConnell et al. (2009). Neuron 2009 64, 93-109DOI: (10.1016/j.neuron.2009.09.001) Copyright © 2009 Elsevier Inc. Terms and Conditions