Articles in 2016

Learning which environmental cues predict harm is paramount to survival, yet evidence for these associations is often ambiguous. The authors demonstrate a critical role for the amygdala in evaluating such ambiguities and show that a computational framework based on structure learning can explain this process.

The lateral entorhinal cortex computes and transfers olfactory information from the olfactory bulb to the hippocampus and supports associative multimodal memories. Leitner et al. characterize the activity of odor-responsive cell types in this brain area and identify upstream and downstream brain areas to which olfactory information is conveyed.

The authors show that artificially enhancing the temporal coordination between hippocampal sharp wave-ripples and cortical delta waves and spindles leads to the reorganization of cortical networks, an increase in their responsivity during recall, and memory consolidation. The study provides causal evidence for the role of hippocampo-cortical interactions during sleep in memory consolidation.

Different neurons in orbitofrontal cortex encode the input and the output of economic decisions. The authors demonstrate that this neural circuit is both stable and flexible. When different goods are available for choice, individual neurons adapt to the new behavioral context while preserving their function in the decision circuit.

The authors show that a gene expression switch operated by microRNAs regulates the control of puberty onset and adult fertility by the CNS by triggering increased hypothalamic Gnrh mRNA expression during the infantile period of postnatal development.

Midbrain dopamine neurons have been implicated in two related but distinct processes: reward learning and action generation. By combining an operant learning task in mice with recordings from projection-defined dopamine neurons, the authors found that dopamine neurons targeting different parts of the striatum carry different information about rewards and chosen actions.

Hyperpolarization and cyclic-nucleotide-gated (HCN) channels shape synaptic integration in the soma and dendrites of many neurons. Here, Ko et al. show that in auditory neurons HCN channels are also present in the axon initial segment, where they influence spike probability and also serve as potent sites for neuromodulation.

Glioblastoma is a deadly brain tumor with no cure. The cytokine receptor OSMR is identified as a new key player in glioblastoma pathogenesis. OSMR orchestrates a feed-forward mechanism with the oncogenic protein EGFRvIII and the transcription factor STAT3 to drive oncogenesis. Loss of OSMR impairs EGFRvIII-STAT3 signaling and glioblastoma tumorigenesis.

The authors reveal that PTB and its homolog nPTB mediate two sequential RNA regulatory loops required for converting human adult fibroblasts to functional neurons, and likely required for neurogenesis in vivo. The first loop, PTB–miR-124–REST, controls initial neuronal conversion and the second, nPTB–miR-9–BRN2, is responsible for neuronal maturation.

The authors used new 3D electron microscopy techniques and analyses to reconstruct virtually all neurons in the olfactory bulb of a zebrafish larva. The results reveal specific patterns of projections between the functional modules of the olfactory bulb, the glomeruli. This network provides an anatomical basis for distributed olfactory computations.

Mechanisms underlying partial functional recovery after spinal cord injury are unclear. Conditionally knocking out the reinduced repulsive axon guidance receptor Ryk led to increased corticospinal axon plasticity and functional recovery. Motor cortex reorganized such that the hindlimb cortex controls the forelimb with continued forelimb reaching task training. A greater cortical area was recruited to control the forelimb in Ryk cKO.

Maximizing information storage in recurrent networks leads to connectivity matrices whose statistics reproduce experimentally observed features of the connectivity between pyramidal cells in cortex. These include a large fraction of potential synapses and an over-representation of bidirectionally connected pairs of neurons, as compared to random networks.

Basal ganglia outputs to the superior colliculus are often associated with eye movements. Using in vivo recording and optogenetic stimulation, the authors demonstrate that a specific GABAergic pathway from the lateral substantia nigra pars reticulata to the lateral superior colliculus is critical for self-initiated drinking behavior, but not for whisking or blinking.

The authors show that glutamatergic neurons, which are intermixed with dopaminergic neurons in the ventral tegmental area, establish multiple excitatory synapses on parvalbumin GABAergic interneurons in the nucleus accumbens. Activation of this glutamatergic mesoaccumbens pathway induces the release of GABA onto medium spiny neurons and drives aversion.

Starving animals are less likely to defend their home territory and more likely to engage in risky foraging behaviors. This work describes a circuit involving hypothalamic AgRP neurons projecting to neurons in the medial nucleus of the amygdala and their projections to the bed nucleus of the stria terminalis, which, when activated, mimics these behaviors in mice that are well fed.

This study identifies SFPQ (splicing factor, poly-glutamine rich) as an RNA binding protein that binds and coassembles multiple mRNAs in axonal transport granules, and thereby promotes neurotrophin-dependent axon survival. These data demonstrate that SFPQ orchestrates spatial gene expression of a newly identified RNA regulon essential for axonal viability.

Zhang et al. show that the poly(GA) proteins produced in patients with C9ORF72 repeat expansions cause neurodegeneration and behavioral abnormalities when expressed in mice. The emergence of these phenotypes requires poly(GA) aggregation, and poly(GA) inclusions sequester HR23 proteins involved in proteasomal degradation, as well as proteins involved in nucleocytoplasmic transport.

The authors analyzed the whole-exome sequences of over 16,000 individuals and found that very rare variants predicted to disrupt the SETD1A gene confer substantial risk for schizophrenia. Damaging variants in SETD1A were also associated with diverse, severe developmental disorders, providing an important genetic link between schizophrenia and other neurodevelopmental disorders.

The authors show that the ventrolateral aspect of the ventromedial hypothalamus (VMHvl), a region previously implicated in attack behavior, can also drive flexible aggression-seeking behavior. When male mice learn a task to seek out attack opportunities, activity in the VMHvl tracks and bidirectionally modulates the seeking behavior that leads to future attack.

Circadian pacemaker neurons help animals synchronize their behavior with 24-hour day–night cycles. The authors identify a neuronal circuit that links Drosophila pacemaker neurons to locomotor activity and sleep centers. They show that the intrinsic neuronal activity rhythms of pacemaker neurons are transmitted through this circuit to generate rhythmic behavior.