This Week in The Journal
Cellular/Molecular
5-HT Activates NTS Neurons by Enhancing Spontaneous Release
Ran Ji Cui, Brandon L. Roberts, Huan Zhao, Mingyan Zhu, and Suzanne M. Appleyard
(see pages 16530–16538)
Afferent information about gut distention and changes in blood pressure activates catecholaminergic (CA) neurons in the solitary tract nucleus (NTS), which regulate food intake and cardiovascular function via projections to the hypothalamus and other brain regions. Serotonin regulates these functions, but how it does so is unclear. Several serotonin receptor subtypes (5-HTRs) are expressed in the NTS, including 5-HT3Rs, which enhance glutamate release from vagal afferent terminals. Because activation of 5-HT3Rs suppresses eating and contributes to cardiovascular reflexes, Cui et al. suspected that activating these receptors increases the activity of CA neurons. Indeed, serotonin increased the frequency of spontaneous EPSCs (sEPSCs) in mouse CA neurons, as did a 5-HT3R agonist that also increased CA neuron firing. The effect did not depend on afferent spiking—in fact, 5-HT3R agonist reduced the amplitude of EPSCs evoked by afferent spiking. Interestingly, in the presence of 5-HT3R antagonist, serotonin reduced sEPSC frequency, suggesting that serotonin can bidirectionally regulate CA neuron activity by acting on different receptor subtypes.
Development/Plasticity/Repair
Psidin Independently Regulates Cell Survival and Axon Growth
Daniel Stephan, Natalia Sánchez-Soriano, Laura F. Loschek, Ramona Gerhards, Susanne Gutmann, et al.
(see pages 16080–16094)
As growing axons navigate to their targets, growth cones at their tips search the local environment for guidance cues. Receptors for these cues promote growth, retraction, or turning through effects on the actin cytoskeleton. To identify novel proteins involved in axon guidance, Stephan et al. looked for pathfinding defects in Drosophila in which mutated proteins were expressed only in the antenna, maxillary palp, and eye. A point mutation in the actin-binding protein Psidin resulted in axon mistargeting by several classes of olfactory receptor neurons (ORNs): mainly those that traveled the longest distances and had to turn to enter the antennal lobe. Interestingly, larger Psidin mutations not only disrupted axon guidance, but also reduced survival of several ORN classes. Overexpressing a protein that inhibits apoptosis rescued the cell survival defect but did not rescue axon pathfinding, whereas mutations in an actin-stabilizing protein that is antagonized by Psidin rescued pathfinding but not survival. Thus, Psidin regulates survival and axon guidance via dissociable pathways.
A growth cone of an embryonic Drosophila neuron growing in culture expresses tubulin (green) and actin (magenta). Neurons lacking Psidin have longer axons and smaller lamellipodia than normal. See the article by Stephan et al. for details.
Behavioral/Systems/Cognitive
Oxytocin Makes Attached Men Stay Away from Other Women
Dirk Scheele, Nadine Striepens, Onur Güntürkün, Sandra Deutschländer, Wolfgang Maier, et al.
(see pages 16074–16079)
Oxytocin, first recognized for its role in triggering uterine contractions during labor, has many important roles in social animals. It promotes maternal and paternal care of offspring, and it is involved in pair-bonding in monogamous prairie voles. Oxytocin levels increase in humans soon after they enter a romantic relationship and after positive physical contact with a partner. Furthermore, intranasal delivery of oxytocin can improve communication in couples, improve discernment of emotions from facial expressions, increase trust and generosity toward group members, and reduce social anxiety. Scheele et al. now provide evidence that oxytocin may help maintain monogamous relationships by influencing men's interactions with unfamiliar, attractive women. When approaching or being approached by an attractive woman, the final interpersonal distance preferred by men in monogamous relationships was similar to that of single men. But intranasal administration of oxytocin caused monogamous men to prefer a greater distance. How best to increase oxytocin in one's partner to achieve such effects has yet to be determined.
Neurobiology of Disease
Reducing Glial Activation Attenuates Alzheimer's Phenotypes
Jennifer L. Furman, Diana M. Sama, John C. Gant, Tina L. Beckett, M. Paul Murphy, et al.
(see pages 16129–16140)
Alzheimer's disease (AD) can result from mutations in amyloid precursor protein or the secretases that cleave it to produce β-amyloid (Aβ), which aggregates and forms plaques. Most AD cases arise sporadically, however. The events leading to Aβ accumulation in these cases are poorly understood, but much evidence suggests that chronic brain inflammation is an important trigger. Neuroinflammation is maintained by reactive astrocytes and microglia, which surround AD plaques and secrete inflammatory agents. The phosphatase calcineurin helps activate astrocytes by dephosphorylating a transcription factor, nuclear factor of activated T cells (NFAT). This signaling pathway is hyperactive in AD. The synthetic peptide VIVIT prevents NFAT dephosphorylation by calcineurin, and thus decreases neuroinflammation. Furman et al. report that expressing VIVIT selectively in hippocampal astrocytes attenuated AD-related phenotypes in a mouse model. Injecting VIVIT-expressing virus in 7-month-old mice reduced glial activation, Aβ, and β-secretase levels 9 months later. Furthermore, VIVIT expression improved performance on a cognitive test and reversed deficits in long-term potentiation.
