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Intrinsic dopamine and acetylcholine dynamics in the striatum of mice
In the absence of reward, dopamine and acetylcholine levels in the striatum fluctuate in a phasic manner, with their dynamics autonomously organized by extra-striatal neurons.
- Anne C. Krok
- , Marta Maltese
- & Nicolas X. Tritsch
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Article |
Kainate receptor modulation by NETO2
The authors report the structures of glutamate-gated kainate receptors in complex with NETO2 in both the resting and the desensitized states and reveal how kainate receptors in the brain are regulated by NETO2.
- Lingli He
- , Jiahui Sun
- & Yan Zhao
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Article |
Structural insights into the activation of metabotropic glutamate receptors
The activation mechanism of metabotropic glutamate receptor subtype 5, a member of the family C G-protein-coupled receptors, is characterized by a combination of cryo-electron microscopy, crystallography and signalling studies.
- Antoine Koehl
- , Hongli Hu
- & Brian K. Kobilka
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Letter |
Cryo-EM structure of the human α1β3γ2 GABAA receptor in a lipid bilayer
A high-resolution cryo-electron microscopy structure is reported for the full-length human α1β3γ2L GABAA receptor, functionally reconstituted in lipid nanodiscs.
- Duncan Laverty
- , Rooma Desai
- & A. Radu Aricescu
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Letter |
Genetic identification of leptin neural circuits in energy and glucose homeostases
A subset of neurons in the hypothalamus is identified as the primary site of action for regulating energy balance and glucose homeostasis by leptin.
- Jie Xu
- , Christopher L. Bartolome
- & Dong Kong
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Brief Communications Arising |
Effects of a ketamine metabolite on synaptic NMDAR function
- Kanzo Suzuki
- , Elena Nosyreva
- & Lisa M. Monteggia
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Letter |
X-ray structure of the human α4β2 nicotinic receptor
Nicotinic acetylcholine receptors are ligand-gated ion channels that mediate fast chemical neurotransmission; here, the first X-ray crystal structure of a nicotinic receptor is reported, revealing how nicotine stabilizes the receptor in a non-conducting, desensitized conformation.
- Claudio L. Morales-Perez
- , Colleen M. Noviello
- & Ryan E. Hibbs
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Outlook |
Perspective: The surgical solution
Not enough doctors and patients opt for surgery to treat epilepsy, despite clinical evidence of the benefits, says Samuel Wiebe.
- Samuel Wiebe
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Outlook |
Neurobiology: Unrestrained excitement
Epilepsy arises from natural mechanisms in the brain that go awry. Researchers are trying to unravel its complexities.
- Michael Eisenstein
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Letter |
Asymmetric neurotransmitter release enables rapid odour lateralization in Drosophila
When an odour activates a fly′s antennae asymmetrically, more neurotransmitter is released from olfactory receptor neuron axon branches ipsilateral to the antenna than from contralateral branches. This causes ipsilateral central olfactory neurons to begin spiking earlier and at a higher rate than contralateral neurons, thereby enabling a walking fly to turn towards the odour.
- Quentin Gaudry
- , Elizabeth J. Hong
- & Rachel I. Wilson
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Letter |
Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning
GABA-releasing neurons from the ventral tegmental area that project to the nucleus accumbens are shown to block the firing of cholinergic accumbal interneurons, affecting learning in mice.
- Matthew T. C. Brown
- , Kelly R. Tan
- & Christian Lüscher
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Letter |
Layered reward signalling through octopamine and dopamine in Drosophila
Dopamine is synonymous with reward in mammals but associated with aversive reinforcement in insects, where reward seems to be signalled by octopamine; here it is shown that flies have discrete populations of dopamine neurons representing positive or negative values that are coordinately regulated by octopamine.
- Christopher J. Burke
- , Wolf Huetteroth
- & Scott Waddell
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News & Views |
Promiscuous vesicles
The unexpected finding that neurons can co-release two neurotransmitter molecules, dopamine and GABA, through a common mechanism provides a further advance in our understanding of the nervous system. See Letter p.262
- John T. Williams
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Review Article |
Molecular machines governing exocytosis of synaptic vesicles
A brief survey of the molecular mechanisms that give the vesicle cycle in intact synapses its efficiency.
- Reinhard Jahn
- & Dirk Fasshauer
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Letter |
Dopaminergic neurons inhibit striatal output through non-canonical release of GABA
Activation of midbrain dopamine neurons rapidly inhibits action potential firing in both direct- and indirect-pathway striatal projection neurons through VMAT2-dependent vesicular release of the inhibitory transmitter GABA (γ-aminobutyric acid).
- Nicolas X. Tritsch
- , Jun B. Ding
- & Bernardo L. Sabatini
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Letter |
Structure and dynamics of the M3 muscarinic acetylcholine receptor
The X-ray crystal structure of the M3 muscarinic acetylcholine receptor bound to the bronchodilator drug tiotropium is reported; comparison of this structure with that of the M2 muscarinic acetylcholine receptor reveals key differences that could potentially be exploited to develop subtype-selective drugs.
- Andrew C. Kruse
- , Jianxin Hu
- & Brian K. Kobilka
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Article |
X-ray structures of LeuT in substrate-free outward-open and apo inward-open states
The X-ray crystal structure of LeuT, the bacterial homologue of the neurotransmitter sodium symporter family, is reported in the outward-open and inward-open states.
- Harini Krishnamurthy
- & Eric Gouaux
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Letter |
Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis
Exposure to cold drives IL-4-mediated alternative macrophage activation and catecholamine secretion in brown and white adipose tissues to stimulate thermogenesis.
- Khoa D. Nguyen
- , Yifu Qiu
- & Ajay Chawla
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Article |
Principles of activation and permeation in an anion-selective Cys-loop receptor
- Ryan E. Hibbs
- & Eric Gouaux
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Letter |
Substrate-modulated gating dynamics in a Na+-coupled neurotransmitter transporter homologue
- Yongfang Zhao
- , Daniel S. Terry
- & Jonathan A. Javitch
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News & Views |
Remarkable role for the placenta
The placenta does not only act as the essential link between the developing embryo and its mother. Unexpectedly, it is also a source of serotonin — a neurotransmitter that is crucial for embryonic brain development. See Letter p.347
- Ron McKay
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Letter |
A transient placental source of serotonin for the fetal forebrain
- Alexandre Bonnin
- , Nick Goeden
- & Pat Levitt
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Article |
A selective role for dopamine in stimulus–reward learning
Humans and animals readily learn to associate neutral cues paired with rewards, but the exact role that dopamine release has in this learning is controversial. Using previously established rat strains selectively bred for many generations to have greater or lesser propensity to assign value to learned cues, this study uses cyclic voltammetry to measure dopamine signals in the different strains and also examines the effect of blocking dopamine. It is concluded that dopamine selectively mediates motivational, rather than predictive, aspects of the cues.
- Shelly B. Flagel
- , Jeremy J. Clark
- & Huda Akil
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News |
Motor disorder could have stress-fighting solution
Research reveals possible cause and potential therapy for Parkinson's disease.
- Janelle Weaver
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Review Article |
Glial and neuronal control of brain blood flow
- David Attwell
- , Alastair M. Buchan
- & Eric A. Newman
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Letter |
Long-term potentiation depends on release of d-serine from astrocytes
The involvement of astroglia in long-term potentiation (LTP) of synaptic transmission remains controversial. Clamping internal Ca2+ in individual astrocytes in the CA1 area of the hippocampus is now shown to block LTP induction at nearby excitatory synapses through an effect on the N-methyl-D-aspartate receptor. This LTP blockade can be reversed by exogenous D-serine, normally released in a Ca2+-dependent manner from astrocytes.
- Christian Henneberger
- , Thomas Papouin
- & Dmitri A. Rusakov
A single photoreceptor splits perception and entrainment by cotransmission
Control of visual cortical signals by prefrontal dopamine