Cellular/Molecular
NG2+ Cells Proliferate and Differentiate without NMDA Receptors
Lindsay M. De Biase, Shin H. Kang, Emily G. Baxi, Masahiro Fukaya, Michele L. Pucak, et al.
(see pages 12650–12662)
Cells expressing the proteoglycan NG2 are present throughout the developing and mature brain. They can self-renew, but they also differentiate into oligodendrocytes, which do not express NG2. Thus, they are generally considered oligodendrocyte precursor cells. Many NG2+ cells remain in the mature brain after oligodendrocytes have been generated, however, suggesting they have other functions besides serving as oligodendrocyte precursors. NG2+ cells express voltage-sensitive ion channels and glutamate receptors and receive synaptic inputs from neurons, which have been proposed to regulate the proliferation and differentiation of NG2+ cells to ensure full myelination of axons. Results by De Biase et al. argue against this hypothesis, however. Deleting an NMDA receptor subunit from mouse NG2+ cells and their progeny did not significantly affect proliferation, migration, morphology, membrane properties, survival, or differentiation of NG2+ cells, and the mice showed no signs of myelin deficiency. Therefore, NMDA receptors appear to perform an as-yet-unknown function in these cells.
3D reconstruction of mouse cortical NG2+ cell lacking NMDA receptor subunit NR1. The morphology appears unaffected by loss of functional NMDA receptors. See the article by De Biase et al. for details.
Development/Plasticity/Repair
BDNF Effect on Dendritic Spines Requires Vav
Carly F. Hale, Karen C. Dietz, Juan A. Varela, Cody B. Wood, Benjamin C. Zirlin, et al.
(see pages 12426–12436)
Morphological changes in neuronal structures such as dendritic spines require remodeling of the actin cytoskeleton. This remodeling is governed in part by Rho-family GTPases, such as Rac, whose activity is enhanced by guanine-nucleotide exchange factors (GEFs). GEFs facilitate the exchange of GDP for GTP, thus recharging GTPases. Because changes in spine shape and size contribute to synaptic plasticity, factors that modulate plasticity are likely to act via GEFs and/or Rho GTPases. One such factor is brain-derived neurotrophic factor (BDNF), which enhances hippocampal long-term potentiation (LTP) and stimulates dendritic spine growth. Hale et al. show that BDNF, acting via TrkB receptors, increases phosphorylation of the GEF Vav. Knock-out of Vav reduced BDNF-induced increases in Rac-GTP levels and spine-head size in mouse hippocampal slices, and it reduced LTP induced by theta-burst stimulation. Although these results suggest that Vav contributes to BDNF-induced spine growth, whether it does so by influencing actin dynamics remains untested.
Behavioral/Systems/Cognitive
Not All Learning Increases Newborn Neuron Survival
Nathalie Mandairon, Sébastien Sultan, Morgane Nouvian, Joelle Sacquet, and Anne Didier
(see pages 12455–12460)
The subventricular zone generates neuronal progenitors throughout life. In adults, newborn progenitors migrate to the olfactory bulb, differentiate into granule cells, and integrate into olfactory circuits. Addition of newborn neurons is required to maintain the population of olfactory granule cells, which continually die. Whether newborn olfactory neurons also have a special role in olfactory learning is unclear, however: some studies indicated that blocking neurogenesis impaired learning, whereas others found no such effect. Mandairon et al. hypothesized that newborn neurons are required for only some types of learning, particularly operant olfactory conditioning, in which animals learn to perform a specific behavior to get a reward when an olfactory stimulus is presented. Operant olfactory conditioning increased the survival and responsiveness of newborn neurons to learned odors. In contrast, non-operant associative conditioning, in which an odor was paired with a reward regardless of behavior, did not significantly affect the survival or activity of newborn neurons.
Neurobiology of Disease
BAC Expression Impairs Function of Striatopallidal Neurons
Vincenza Bagetta, Barbara Picconi, Silvia Marinucci, Carmelo Sgobio, Valentina Pendolino, et al.
(see pages 12513–12522)
Medium spiny neurons (MSNs) are the predominant neuron type in the striatum. Two populations of MSNs are intermingled: striatonigral MSNs directly inhibit output nuclei of the basal ganglia and express D1-type dopamine receptors (D1DRs), while striatopallidal MSNs indirectly excite output nuclei and express D2DRs. Balancing direct and indirect pathways is thought to be essential for motor control, and plasticity in these pathways underlies motor learning. Early studies suggested that cortical inputs onto both types of MSNs undergo dopamine-dependent long-term depression (LTD). When bacterial artificial chromosomes (BAC) were used to specifically label striatonigral or striatopallidal MSNs in mice, however, only striatopallidal MSNs exhibited LTD. Remarkably, Bagetta et al. provide evidence that BAC expression prevents expression of LTD in striatonigral MSNs. When immunostaining was used to distinguish MSNs after recording, it revealed that LTD occurred similarly in striatonigral and striatopallidal neurons. Moreover, BAC expression in striatonigral MSNs caused behavioral changes, suggesting striatal function is disrupted in these mice.
