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The subependymal zone (SEZ) is a neurogenic niche that gives rise to adult-born neurons. Paez-Gonzalez and colleagues describe a population of cholinergic neurons in this region that modulates neural progenitor proliferation. The cover depicts a SEZ cholinergic neuron (red) along with surrounding stem cells and newborn neuroblasts (teal). Cover image by Chay Kuo.897934
The orbitofrontal cortex and ventral striatum encode expected outcomes during economic decision-making. Research now demonstrates that activity in these structures also represents missed opportunities during a foraging task cleverly designed to elicit regret in rats, the Restaurant Row task.
A report reveals that giant subcortical heterotopia is caused by mutation of a microtubule-associated protein, Eml1. Defects in Eml1 lead to disruption of the radial migratory scaffolding network in mice and humans.
A leading therapeutic molecule for multiple sclerosis, FTY720, is shown to mimic a key component of sphingolipid signaling, resulting in specific manipulation of histone deacetylases and the extinction of memory.
The proliferation of NSCs in the adult SVZ is controlled by a set of neurons expressing choline acetyltransferase, identifying a mechanism connecting brain activity to neurogenesis in the adult mammalian brain.
This Review discusses the molecular mechanisms by which neuronal identity is maintained throughout animals' development and lives. Drawing from the invertebrate and vertebrate literature, Deneris and Hobert also describe common themes, where the initial specification of neurons and subsequent maintenance of cell identity may share transcriptional programming and transcription factors. The piece also discusses such mechanism's implications for neurological diseases.
In this study, the authors show that conditional deletion of leptin receptors from astrocytes alters their morphology and results in an increase in the number of synapses on POMC and AgRP neurons of the arcuate nucleus. In addition, they find that loss of leptin response in astrocytes modified leptin- and ghrelin-controlled food intake.
Melanocortin 4 receptors (MC4Rs) in the CNS regulate metabolism. Here the authors examine extra-hypothalamic MC4Rs in the autonomic nervous system and find that they contribute to energy and glucose homeostasis.
To address how agonist binding is transduced into pore opening in NMDARs, the authors manipulated the coupling between the ligand binding domain (LBD) and the ion channel and performed computational and thermodynamic analyses. Based on this data, they conclude that NMDAR-mediated synaptic response relies on a mechanical coupling between the LBD and the ion channel.
Kielar and colleagues identified mutations in the microtubule-associated protein Eml1 in patients with severe cortical heterotopia. Using animal and cell models, the authors found that Eml1 inactivation alters spindle orientation in dividing neuronal progenitors during early corticogenesis, leading to their detachment from the ventricular zone, their accumulation in the intermediate zone and the subsequent development of subcortical heterotopia.
This study describes a novel population of cholinergic neurons in the adult subependymal zone (SEZ) of mouse that modulates neural progenitor proliferation. These ChAT+ neurons in the SEZ display neuronal activity-dependent release of acetylcholine locally and stimulate neurogenesis accordingly.
In this study, the authors show that TGF-β/ALK5 and JNK signaling is necessary during the late stages of adult neurogenesis to promote the survival, migration and proper morphology of newborn neurons. In addition, constitutive activation of this pathway is able to promote improved performance on spatial and contextual learning tasks.
Unlike that of its main counterpart, the functional organization of the accessory olfactory bulb, important for detecting socially relevant odors, remains to be detailed. Here the authors map out Ca2+ signals from vomeronasal inputs to the accessory olfactory bulb in response to socially relevant compounds and find a non-chemotopic spatial organization.
In Drosophila melanogaster, descending interneurons known as giant fibers (GFs) are associated with escape behavior. The authors demonstrate that a synthetic looming predator stimulus can trigger GF-mediated short escape and parallel circuit–mediated long escape modes, and the relative spike timing between these circuits determines which escape mode is elicited.
Fingolimod is a sphingosine-1 phosphate (S1P) receptor modulator and an immune modulator in use as a treatment for the remitting-relapsing form of multiple sclerosis. Hait et al. show that the active form of fingolimod can inhibit neuronal class I histone deacetylases (HDACs), modulate gene expression in the brain and facilitate memory extinction. The authors also show spatial and associative memory deficits in mutant mice lacking the enzyme necessary for formation of the active form of fingolimod.
Using a modified water-maze paradigm involving a spatial distribution of platform locations across training days, the authors found that mice were better able to match platform distributions at later time points after training. Mice also showed greater sensitivity to new, conflicting platform locations at later time points, and this sensitivity depended on the medial prefrontal cortex.
Using two-photon imaging of neuronal activity in mouse motor cortex during the acquisition of a self-initiated lever-pull task, Masamizu and colleagues demonstrate that learning is accompanied by a reorganization of ensemble activity in layer 5a. This reorganization correlates with an increase in ensemble prediction of task accuracy. The authors also find that no such changes take place in layer 2/3.
In situations that would be expected to induce regret, the authors report that rats looked backwards towards a lost option, the cells in OFC and ventral striatum represented that missed action, rats were more likely to wait out a long delay, and then they rushed through consuming rewards, suggesting that regret-like processes modify decision-making in nonhuman mammals.
To help identify critical sources of attentional feedback to area V4, the authors surgically deprived V4 of PFC input in one hemisphere while keeping the other hemisphere intact. In the absence of PFC, attentional effects on neuronal responses and synchrony in V4 were significantly reduced and the remaining effects of attention were delayed in time.