Hot off the presses! Jan 01 Nat Rev Neurosci

The Jan 01 issue of the Nat Rev Neurosci is now up on Pubget (About Nat Rev Neurosci): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Neurodevelopmental disorders: Getting with the reprogram | PDF (369 KB)
  - Nat Rev Neurosci 13(1):1 (2012)
  Timothy syndrome is a rare monogenic neurodevelopmental disorder that can be associated with autism. The underlying genetic defect in this syndrome is a point mutation in CACNA1C, which is the gene that encodes the α1 subunit of the L-type voltage-gated calcium channel Cav1.2.
• Neural development: From floorplate to function | PDF (386 KB)
  - Nat Rev Neurosci 13(1):2 (2012)
  Although directed differentiation of embryonic stem cells into dopaminergic neurons has been demonstrated in vitro, their ability to promote functional recovery in models of Parkinson's disease has been limited. A new study now demonstrates a method of obtaining floorplate-derived engraftable dopaminergic neurons from human pluripotent stem cells (PSCs).
• Neuronal networks: In the rich club | PDF (249 KB)
  - Nat Rev Neurosci 13(1):3 (2012)
  Within the brain's networks, certain key regions have been revealed to be 'hubs' — they form many connections with other brain areas and have a large influence on overall network organization. In a new study, van den Heuvel and Sporns now show that these hub regions are also highly mutually interconnected, forming a 'rich club' of brain areas that are crucial for efficient brain communication.
• Neurodevelopmental disorders: A fragile synaptic balance | PDF (225 KB)
  - Nat Rev Neurosci 13(1):3 (2012)
  A number of specific gene mutations are associated with intellectual disability and autism, providing hope that understanding common downstream effects might shed light on the pathophysiology of autism spectrum disorders. Bear and colleagues now show that mutations in fragile X mental retardation 1 (FMR1) and tuberous sclerosis 2 (TSC2), which are associated with similar behavioural impairments, have opposing effects on metabotropic glutamate receptor 5 (mGluR5) function and synaptic protein synthesis.
• Learning and memory: Channelling spatial information | PDF (305 KB)
  - Nat Rev Neurosci 13(1):4 (2012)
  Grid cells in the entorhinal cortex provide a two-dimensional metric of the spatial environment. Together with head direction cells and conjunctive cells, they integrate information about a moving animal's trajectory and convey this information to place cells in the hippocampal CA1 and CA3 subregions.
• Psychiatric disorders: Multiple pathways to DISC1-related disease? | PDF (272 KB)
  - Nat Rev Neurosci 13(1):4 (2012)
  The scaffolding protein disrupted in schizophrenia 1 (DISC1) has multiple roles in neurodevelopment. Both rare and common variants of this protein may influence psychiatric phenotypes, although it remains unclear how DISC1 is mechanistically linked to disease.
• Neurotransmission: Dissecting co-transmission in the striatum | PDF (254 KB)
  - Nat Rev Neurosci 13(1):5 (2012)
  Understanding the regulation of neurotransmission is key to uncovering new strategies for the treatment of motor diseases. Whereas the role of dopamine in the regulation of medium spiny GABAergic neurons (MSNs; the major output neurons of the striatum) is well characterized, much less is known about the role of striatal cholinergic activity.
• Perception: Excitability modulates synaesthesia | PDF (83 KB)
  - Nat Rev Neurosci 13(1):2 (2012)
  Synaesthetes who experience colours when perceiving or representing numbers exhibit structural and functional differences in cortical areas that are involved in number and colour processing compared to non-synaesthetes. Using transcranial magnetic stimulation or transcranial direct current stimulation, the authors showed that in humans, grapheme-colour synaesthesia is characterized by enhanced cortical excitability in the primary visual cortex and can be augmented or attenuated with cathodal or anodal stimulation, respectively.
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  - Nat Rev Neurosci 13(1):2 (2012)
  
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  - Nat Rev Neurosci 13(1):2 (2012)
  
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  - Nat Rev Neurosci 13(1):2 (2012)
  
• Nanodomain coupling between Ca2+ channels and sensors of exocytosis at fast mammalian synapses
  - Nat Rev Neurosci 13(1):7 (2012)
  The physical distance between presynaptic Ca2+ channels and the Ca2+ sensors that trigger exocytosis of neurotransmitter-containing vesicles is a key determinant of the signalling properties of synapses in the nervous system. Recent functional analysis indicates that in some fast central synapses, transmitter release is triggered by a small number of Ca2+ channels that are coupled to Ca2+ sensors at the nanometre scale. Molecular analysis suggests that this tight coupling is generated by protein–protein interactions involving Ca2+ channels, Ca2+ sensors and various other synaptic proteins. Nanodomain coupling has several functional advantages, as it increases the efficacy, speed and energy efficiency of synaptic transmission.
• The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission
  - Nat Rev Neurosci 13(1):22 (2012)
  Mounting evidence suggests that acute and chronic stress, especially the stress-induced release of glucocorticoids, induces changes in glutamate neurotransmission in the prefrontal cortex and the hippocampus, thereby influencing some aspects of cognitive processing. In addition, dysfunction of glutamatergic neurotransmission is increasingly considered to be a core feature of stress-related mental illnesses. Recent studies have shed light on the mechanisms by which stress and glucocorticoids affect glutamate transmission, including effects on glutamate release, glutamate receptors and glutamate clearance and metabolism. This new understanding provides insights into normal brain functioning, as well as the pathophysiology and potential new treatments of stress-related neuropsychiatric disorders.
• Gains or losses: molecular mechanisms of TDP43-mediated neurodegeneration
  - Nat Rev Neurosci 13(1):38 (2012)
  RNA-binding proteins, and in particular TAR DNA-binding protein 43 (TDP43), are central to the pathogenesis of motor neuron diseases and related neurodegenerative disorders. Studies on human tissue have implicated several possible mechanisms of disease and experimental studies are now attempting to determine whether TDP43-mediated neurodegeneration results from a gain or a loss of function of the protein. In addition, the distinct possibility of pleotropic or combined effects — in which gains of toxic properties and losses of normal TDP43 functions act together — needs to be considered.
• Normalization as a canonical neural computation
  - Nat Rev Neurosci 13(1):51 (2012)
  There is increasing evidence that the brain relies on a set of canonical neural computations, repeating them across brain regions and modalities to apply similar operations to different problems. A promising candidate for such a computation is normalization, in which the responses of neurons are divided by a common factor that typically includes the summed activity of a pool of neurons. Normalization was developed to explain responses in the primary visual cortex and is now thought to operate throughout the visual system, and in many other sensory modalities and brain regions. Normalization may underlie operations such as the representation of odours, the modulatory effects of visual attention, the encoding of value and the integration of multisensory information. Its presence in such a diversity of neural systems in multiple species, from invertebrates to mammals, suggests that it serves as a canonical neural computation.
• Direct electrical stimulation of human cortex — the gold standard for mapping brain functions?
  - Nat Rev Neurosci 13(1):63 (2012)
  Despite its clinical relevance, direct electrical stimulation (DES) of the human brain is surprisingly poorly understood. Although we understand several aspects of electrical stimulation at the cellular level, surface DES evokes a complex summation effect in a large volume of brain tissue, and the effect is difficult to predict as it depends on many local and remote physiological and morphological factors. The complex stimulation effects are reflected in the heterogeneity of behavioural effects that are induced by DES, which range from evocation to inhibition of responses — sometimes even when DES is applied at the same cortical site. Thus, it is a misconception that DES — in contrast to other neuroscience techniques — allows us to draw unequivocal conclusions about the role of stimulated brain areas.
• Correspondence: Imaging hippocampal subregions with in vivo MRI: advances and limitations
  - Nat Rev Neurosci 13(1):70 (2012)
  In their recent Review article (A pathophysiological framework of hippocampal dysfunction in ageing and disease. Nature Rev. Neurosci., 585–601 (2011)