Development/Plasticity/Repair
Periostin Promotes Axon Growth after Spinal Cord Injury
Chung-Hsuan Shih, Michelle Lacagnina, Kelly Leuer-Bisciotti, and Christoph Proschel
(see pages 2438–2443)
Functional recovery after spinal cord injury is prevented in part by the formation of a glial scar that impedes axon growth through the lesion. When glial-restricted progenitors (GRPs) from embryonic spinal cord are treated with bone morphogenetic protein 4 (BMP4), however, they differentiate into a type of astrocytes (GDAsBMP) that promotes axon regrowth and functional recovery when transplanted into hemisected rat spinal cord. Shih et al. have now identified the protein periostin as the primary mediator of GDAsBMP's beneficial effects. Periostin—which was previously found to promote proliferation, adhesion, migration, and regeneration in muscle and skin—was secreted by GDAsBMP, but not by undifferentiated GRPs or by a different type of astrocytes derived from GRPs. Knocking down periostin in GDAsBMP eliminated the beneficial effects of these cells when transplanted into injured spinal cord. Moreover, recombinant periostin promoted neurite extension in cerebellar and dorsal root ganglion neurons in vitro, even when the cells were plated on inhibitory substrates.
Systems/Circuits
Some Centrolateral Amygdala Neurons Project to Brainstem
Mario A. Penzo, Vincent Robert, and Bo Li
(see pages 2432–2437)
The amygdala is essential for the acquisition and expression of conditioned fear responses. When information about conditioned and unconditioned stimuli converges on neurons in the amygdala's basolateral nuclei (BLA), the neurons learn to fire when the conditioned stimulus is presented by itself. Fear conditioning also strengthens excitatory inputs onto somatostatin-expressing (SOM+) GABAergic neurons in the lateral subdivision of the central amygdala (CeL) to which the BLA projects. SOM+ neurons are reciprocally connected with SOM-negative GABAergic CeL neurons, whose excitatory inputs are weakened during fear conditioning. But only SOM-negative CeL neurons project to the central amygdala's medial subdivision (CeM), whose neurons initiate defensive responses via projections to the midbrain periaqueductal gray (PAG) and thalamic paraventricular nucleus (PVT). Therefore, SOM+ neurons are thought to initiate fear responses primarily by inhibiting SOM-negative neurons and disinhibiting CeM neurons. But Penzo et al. have discovered that many SOM+ CeL neurons also project to the PAG and/or PVT and might thereby initiate conditioned fear responses more directly.
Behavioral/Cognitive
Calcineurin Underlies Reconsolidation–Extinction Transition
Emiliano Merlo, Amy L. Milton, Zara Y. Goozée, David Theobald, and Barry J. Everitt
(see pages 2422–2431)
Associations between conditioned (CS) and unconditioned stimuli (US) learned during fear conditioning are stored in the amygdala. When a CS is presented once without its US, the negative association is reconsolidated and fear responses are retained, but only if NMDA receptors are activated. After several unpaired presentations of the CS, rats learn that the CS is not always dangerous; they form a new association that leads to inhibition of the fear response. This learning, called extinction, also requires NMDA receptors, but it involves a separate population of amygdala neurons. Merlo et al. found that blocking NMDA receptors after four CS presentations left fear responses unchanged, suggesting that neither extinction nor reconsolidation predominated at that point. More importantly, they found that the transition from reconsolidation to extinction involved increases in the phosphatase calcineurin in the amygdala. Calcineurin levels were positively correlated with the number of CS presentations and inversely correlated with fear expression. Moreover, knocking down calcineurin inhibited extinction but not reconsolidation.
Neurobiology of Disease
Interleukin-1β Impairs Cognition in Obese Mice
Joanna R. Erion, Marlena Wosiski-Kuhn, Aditi Dey, Shuai Hao, Catherine L. Davis, et al.
(see pages 2618–2631)
Obesity—specifically, excessive visceral (“belly”) fat—increases the risk of numerous diseases, including diabetes, atherosclerosis, and dementia. Many of the negative health effects of obesity are attributed to a chronic state of low-grade inflammation induced by proinflammatory macrophages. Macrophage numbers are elevated in adipose tissue of obese individuals, and cytokines produced by macrophages cause insulin resistance. Erion et al. present evidence that such cytokines also impair cognitive function. Genetically obese mice performed poorly on memory tasks, showed deficits in long-term potentiation (LTP), and had fewer synapses than wild-type mice. Furthermore, macrophage numbers and levels of the proinflammatory cytokine interleukin-1β were elevated in obese mice. Treadmill exercise reduced visceral fat, macrophage number, and interleukin-1β levels while reverting memory-task performance, LTP, and synapse number to wild-type levels. Surgically removing fat pads produced results similar to those of exercise, as did infusing an interleukin-1β receptor antagonist into the hippocampus. In contrast, transplanting fat into wild-type mice increased signs of inflammation and reduced memory performance, LTP, and synaptic number.
The number of dendritic spines on dentate granule cells is reduced in the hippocampus of obese mice, but recovers after fat pads are removed. See the article by Erion et al. for details.
