Cellular/Molecular
IL-1RAcP and PTPδ Are a Synaptogenic Pair
Tomoyuki Yoshida, Tomoko Shiroshima, Sung-Jin Lee, Misato Yasumura, Takeshi Uemura, et al.
(see pages 2588–2600)
For efficient synaptic transmission, presynaptic release sites must be precisely aligned with postsynaptic specializations. This is ensured by trans-synaptic communication mediated largely by synaptic adhesion complexes. Heterophilic interaction between presynaptic and postsynaptic receptors recruits intracellular proteins to form complexes on both sides of the synapse, thus coordinating presynaptic and postsynaptic differentiation. Yoshida et al. report that the postsynaptic interleukin-1 receptor accessory protein (IL-1RAcP) and presynaptic protein tyrosine phosphatase (PTP) δ form such a synaptogenic pair. Expression of these proteins in fibroblasts increased aggregation, indicating they are heterophilic adhesion molecules. Furthermore, contact with IL-1RAcP-expressing fibroblasts induced presynaptic differentiation in axons of cultured mouse cortical neurons, whereas contact with PTPδ-coated beads induced postsynaptic differentiation. These effects were eliminated in neurons lacking PTPδ or IL-1RAcP, respectively. In addition, knockdown of IL-1RAcP reduced formation of both presynaptic puncta and dendritic protrusions in cultured neurons, and spine density was reduced on pyramidal neurons of IL-1RAcP-null mice.
Fibroblasts (green) do not normally (top row) induce presynaptic puncta (red) in axons (blue), but fibroblasts expressing IL-1RAcP (bottom row) do. See the article by Yoshida et al. for details.
Development/Plasticity/Repair
Monocular Occlusion Does Not Disrupt V1–V2 Projections
Lawrence C. Sincich, Cristina M. Jocson, and Jonathan C. Horton
(see pages 2648–2656)
Monocular occlusion early in life, which can result from congenital cataracts, impairs vision through the affected eye even after the occlusion has been removed. Impairment occurs primarily because competition between thalamocortical projections representing each eye favors those from the undeprived eye; these projections therefore expand to innervate wider swaths of V1, while those representing the occluded eye are pruned. Whether V1 projections to higher cortical areas are affected by monocular deprivation is unknown. Because projections from each eye's ocular dominance columns in V1 converge on cells in V2, additional competition might amplify the loss of representation of the deprived eye. According to Sincich et al., however, this does not occur. Neurons in deprived and undeprived columns were similarly labeled by retrograde tracers, suggesting their terminal arbor sizes were similar. Furthermore, although most projections to V2 came from neurons in undeprived columns, the reduction could be attributed solely to shrinkage of the deprived columns.
Behavioral/Systems/Cognitive
Corticoamygdalar Projections Reduce Risky Choices
Jennifer R. St. Onge, Colin M. Stopper, Daniel S. Zahm, and Stan B. Floresco
(see pages 2886–2899)
When choosing among possible actions, animals compare the size and probability of different outcomes. Studies using functional imaging or lesions have identified several brain areas involved in such evaluations, including the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC). Little is known about how these areas interact, however. St. Onge et al. discovered that projections from mPFC to BLA follow a different course than axons from BLA to mPFC, allowing selective inhibition of unidirectional communication. Normal rats performed a large-reward action more often than a small-reward action when reward probabilities were high for both, but as the probability of receiving the large reward decreased, rats chose the small reward more often. When mPFC–BLA projections were inhibited, rats continued to choose the low-probability large-reward option, whereas inhibiting BLA–mPFC projections did not alter behavior. The results suggest that projections from mPFC to BLA inhibit actions that are no longer profitable.
Neurobiology of Disease
Disrupting Phagocytosis Attenuates Neuronal Loss
Michael Fricker, Jonas J. Neher, Jing-Wei Zhao, Clotilde Théry, Aviva M. Tolkovsky, et al.
(see pages 2657–2666)
Phagocytosis of dying cells prevents release of toxic intracellular enzymes and helps to resolve inflammation. Phagocytes identify dying cells by their expression of phosphatidylserine (PS), which is sequestered in the inner leaflet of the plasma membrane in healthy cells, but moves to the outer leaflet as cells die. Opsonins, such as the milk-fat globule protein MFG-E8, bind to PS and to vitronectin receptors (VRs) on phagocytes, and thus trigger phagocytosis. But PS externalization can sometimes be induced in viable cells: for example, activated microglia release peroxynitrite, which induces PS externalization in neurons. This can induce microglia to engulf viable neurons. Fricker et al. show that the inflammatory agent lipopolysaccharide (LPS) induced mouse microglia to phagocytose neurons. But neurons showed no signs of apoptosis, and removing microglia prevented neuronal loss, suggesting phagocytosed neurons were otherwise viable. Importantly, preventing MFG-E8 from binding either to PS or to VRs prevented LPS-induced neuronal loss both in vitro and in vivo.
