Research articles

This study shows that TMEM16C facilitates Slack potassium channel activity in the dorsal root ganglia in rats. By generating a gene knockout rat and using electrophysiology, the authors show that TMEM16C modulates mechanical and thermal pain processing by associating with Slack to enhance sodium-activated potassium channel activity.

In this study, Mazzoni et al. describe the mechanism behind the combinatorial action of transcription factors in cell type specification. Specifically, the authors reveal that Isl1 cooperates with Phox2a or Lhx3 in programming modules that regulate differential specification of spinal motor neurons vs. cranial motor neurons.

In this study, the authors show that oligodendrocyte differentiation and remyelination after a CNS lesion coincides with a switch in microglial/macrophage polarization from a pro-inflammatory, M1, phenotype to an anti-inflammatory, M2, phenotype. This M2-dependant effect was in part mediated by secretion of the TGFβ family member, Activin-A.

The authors manipulate AMPAR subunits and transmembrane AMPAR regulatory proteins (TARPs) in cerebellar granule cells lacking the TARP stargazin (also called γ-2). They report that TARP γ-7 selectively enhanced synaptic expression of calcium-permeable AMPARs and suppressed calcium-impermeable AMPARs, suggesting that both γ-2 and γ-7 modulate AMPA transmission in these cells.

Rapid action suppression is often modeled as a race between 'Go' and 'Stop' processes, but how this corresponds to brain mechanisms has been unclear. The authors recorded simultaneously from multiple rat basal ganglia structures during a Stop-signal task and found Go-related activity in striatum and stop-related activity in the subthalamic nucleus. These distinct signals provide convergent, competing influences over individual cells in the substanti anigra pars reticulata, whose activity reflects whether stopping is successful or not. The results tie together neurophysiology and psychological theory to provide a mechanistic account of how we can or cannot cancel forthcoming actions.

Examining the molecular mechanism behind neuronal genomic stability, Dobbin et al. show that the histone lysine deacetylases HDAC1 and SIRT1 are recruited to the sites of DNA double-strand breaks in neurons and demonstrate the importance of HDAC1-SIRT1 functional interactions in DNA double strand–break repairs. The authors also show that pharmacological activation of SIRT1 can stimulate HDAC1 activity and confer neuroprotection after DNA damage in cultured neurons and in two mouse models of neurodegeneration.

The authors study the lineal origins of norepinephrine (NE) neurons in the mouse hindbrain. They identify four genetically separable subpopulations of NE neurons, each with distinct anatomical location, axonal morphology and pattern of efferent projections. One unexpected finding is a projection to the prefrontal cortex that originates from outside the locus coeruleus.

In the hippocampus, coordinates in space are thought to be expressed by the collective firing locations of place cells while the diversity of experience at these locations is encoded by orthogonal variations in firing rates. Here the authors show that these rate variations in CA3 place cells depend on inputs from the lateral entorhinal cortex.

In this paper, Hunt and colleagues provide the first demonstration of bidirectional plasticity of NMDA receptor–mediated synaptic transmission at the hippocampal mossy fiber to CA3 synapse in rats. They also show that this form of long-term plasticity can influence CA3 burst firing and spike temporal fidelity, and exert bidirectional metaplastic control over plasticity at associational-commissural synapses.

In this study, the authors show that MGE- and CGE-derived GABAergic interneurons exhibit differences in their synaptic receptor composition. In particular, they find that MGE-derived interneuron synapses are dominated by calcium-permeable, GluA2-lacking AMPARs, whereas CGE-derived interneurons use both NMDARs and GluA2-containing AMPARs.

This study finds a counterintuitive reduction in neuron bursting during spatial attention. This is explained by a conductance-based model, which also provides a unified explanation for other forms of attentional modulation and correctly predicts the surprising finding that attention decreases action-potential amplitude.

In this study, the authors show that the spatial responses of populations of grid cells are constrained to a two-dimensional activity manifold, and the relationships between pairs of grid cells are resistant to perturbation. These findings provide evidence of low-dimensional continuous attractor dynamics in the network.

Primary somatosensory cortex (S1) contains a map of the body that mirrors maps in hindbrain and thalamus. During development, peripheral changes alter the map in S1. Here the authors use a mouse mutation that alters S1 size and leads to plasticity in the S1 map that is transferred to the thalamic map.

Corticostriatal NMDARs mediate certain learning and executive functions. Here Brigman et al. demonstrate that the NMDAR GluN2B subunit in dorsolateral striatum of mice is important for learning a behavioral choice and that its action is dissociable from that of GluN2B in orbitofrontal cortex in flexibly shifting choice behavior.

The authors show that optogenetic inhibition of inputs from medial prefrontal cortex (mPFC) or insula to the nucleus accumbens core (NAcore) inhibits aversion-resistant alcohol intake. Alcohol-drinking rats showed increased hyperpolarization-active NMDARs at mPFC and insula inputs to NAcore medium spiny neurons. Knocking down these receptors in the NAcore inhibited aversion-resistant alcohol intake.

Joubert syndrome, a recessive neurodevelopmental disorder associated with cortical malformations and autism-like features, has been linked to mutations in the gene encoding Arl13b, a cilia-enriched small GTPase. Here, Higginbotham and colleagues show that the early loss of function of Arl13b in mouse cortical progenitors leads to deficits in progenitors' ciliary signaling, apical–basal inversion of the radial glial scaffold and neuronal misplacement.

Previous studies have shown genome-wide associations between polymorphisms in the gene FTO (fat mass and obesity associated) and type 2 diabetes and obesity, and genetic manipulation of Fto in mice causes feeding dysregulation and body weight changes. Here Hess et al. show that FTO affects the activity and function of midbrain dopaminergic neurons and subsequent reward-related behaviors. The study also shows that FTO acts as a demethylating enzyme for specific mRNAs in vivo, including mRNAs in the dopaminergic signaling pathway.

Using a combination of optogenetics, single-cell molecular profiling and paired electrophysiological recordings in the mouse visual cortex, Pfeffer and colleagues derived the connectivity matrix of three major classes of interneurons with their post-synaptic GABAergic targets. This study provides a comprehensive overview of the wiring rules of the inhibition of inhibition in the cortex.

To investigate how visual input is combined with information about the current task, the authors recorded neural responses in inferotemporal (IT) and perirhinal (PRH) cortex as macaque monkeys performed a match to sample task. Although both areas represented similar amounts of information, extracting the behaviorally relevant information was easier in PRH.

The authors show that reconsolidation of alcohol-related memories activates mammalian target of rapamycin complex 1 (mTORC1) in select amygdalar and cortical regions and systemic or central amygdalar inhibition of mTORC1 during reconsolidation disrupts alcohol-associated memories, leading to a long-lasting suppression of relapse, suggesting a potential therapeutic target to prevent relapse.