Several participants have asked for suggestions of recent papers of general interest in the field of neuroscience.
Le-Qing Wu and J. David Dickman (2012) Neural Correlates of a Magnetic Sense. Science 25 May 2012: 336 (6084), 1054-1057.Published online 26 April 2012 [DOI:10.1126/science.1216567].
This paper reports on electrophysiological recordings from vestibular neurons in pigeons a significant number of cells that respond selectively to the earth's magnetic field in particular directions at the level of magnetic fields normally measured from the earth's own magnetic field.
Lefebvre JL, Kostadinov D, Chen WV, Maniatis T, Sanes JR. (2012) Protocadherins mediate dendritic self-avoidance in the mammalian nervous system. Nature. 2012 Aug 23;488(7412):517-21.
How the the dendrites of adjacent neurons avoid overlapping with each other? This paper addresses this question and explores the role of proto-cadherin molecules, surface proteins that regulate cell adhesion.
Kong, A., et al., Rate of de novo mutations and the importance of father/'s age to disease risk. Nature, 2012. 488(7412): p. 471-475.
A detailed study of 70 or so families in Iceland reveals a strong correlation between the age of the father when he conceives a child, and the number of somatic mutations in the offspring. This important study has implications for mutations in brain cells which express more genes than any other organ in the body. The authors speculate that the recent rise in diagnosed cases of autism might relate to an increased number of mutations related to the age of fathers.
Kindt KS, Finch G, Nicolson T. (2012) Kinocilia mediate mechanosensitivity in developing zebrafish hair cells. Dev Cell. 2012 Aug 14; 23(2):329-41.
"Hair cell mechanotransduction occurs through the displacement of stereociliary bundles. Each stereocilium is connected to others via cadherin-based tip links, and it is believed that tip link tension is instrumental in gating mechanosensitive ion channels. The growth of stereociliary bundles in hair cells is preceded by the emergence of a true cilium, the kinocilium. In this fascinating study, Kindt and colleagues use novel calcium-imaging techniques to show that mechanotransduction can be detected in nascent hair cells earlier than previously believed and that this precocious mechanosensitivity requires the kinocilium. The authors then use technically demanding electrophysiological recording followed by scanning electron microscopy in the same cells to show that the degree of early mechanosensitivity correlates with the appearance of cadherin-based links between the kinocilium and the hair bundle stereocilia, but well before the appearance of mature stereocilia tip links.
Although this is certainly not the first example of cilia participating in mechanosensitivity, this is the first time it has been demonstrated in hair cells. The significance of this early sensitivity is not yet understood, although the authors speculate it may be required for the survival of nascent hair cells. " From Andy Groves - Faculty of 1000 website.
Charlesworth JD, Warren TL, Brainard MS. (2012) Covert skill learning in a cortical-basal ganglia circuit. Nature. 2012 Jun 14; 486(7402):251-5
" This outstanding paper demonstrates that a feedback loop between cortex and basal ganglia can mediate latent acquisition of a sensory-motor skill. The authors show that basal ganglia circuits can monitor motor output (via an efference copy) and its sensory consequences even when their output is inactivated and cannot immediately modify ongoing behavior; when inactivation of this circuit is removed, skilled performance is immediately implemented.
The key to this study is the use of a songbird that can modify its song dependent on sensory input. The circuitry required for this ability is complex and includes an output region (robust nucleus of the arcopallium [RA] -- similar to motor cortex) that controls the frequency of individual song notes. RA receives excitatory input (AMPA plus NMDA receptors) from a premotor area (high vocal center [HVC]) and this circuit (HVC->RA->song motor output), by itself, can drive stereotyped song output. The key to the plasticity of the core song control circuit is an 'anterior forebrain pathway' (AFP). This consists of a basal ganglia region (Area X) in receipt of a song efference copy input from HVC. Area X then, via a thalamic link (dorsolateral thalamus [DLM]), projects to a second cortical region (LMAN). LMAN in turn also has an excitatory projection to RA (NMDA receptors only), thus completing a side loop (HVC->Area X->DLM->LMAN->RA) known to cause variation in song output ('motor exploration'). AFM-induced variation of song structure is believed to be important for ongoing auditory-dependent modification of song performance.
The authors used precisely timed tone bursts to cause the bird to modify the frequency of individual song notes. Inactivating the AFP output (muscimol infusion in LMAN) during the training procedure completely prevented this form of sensory-motor learning. When the AFP was left intact, but its projection to RA selectively blocked (by an NMDA receptor antagonist), no modification of the song syllable frequency occurred during the training protocol. Most remarkably, after the NMDA receptor blockade was lifted, the bird immediately shifted the syllable frequency in an entirely appropriate manner. The authors were able to conclude that the AFP, by comparing the intended motor output with the consequent sensory input, was capable of generating an appropriate correction to the motor output, even though this learning remained confined within the AFP itself and was only expressed after its output was reinstated (after learning was complete). As carefully discussed by the authors, these exciting results will have important implications for the actor-critic model devised to explain basal ganglia-dependent trial and error learning of mammals." -- Leonard Maler (Faculty of 1000, Exceptional)
Senthilan PR, Piepenbrock D, Ovezmyradov G, Nadrowski B, ..., Winkler M, Möbius W, Howard J, Göpfert MC. (2012) Drosophila auditory organ genes and genetic hearing defects. Cell. 2012 Aug 31; 150(5):1042-54
"This paper uses Drosophila genetics and microarray analysis to compile a treasure trove of 274 genes that are enriched in the fly auditory organ, Johnston's organ (JO). The authors provide compelling functional evidence that many of the genes (27 out of 42 tested) affect hearing when mutated. 217 of the genes identified by the authors have mouse or human orthologs, and some of these have previously been implicated in deafness in humans or mice. It is highly likely that many of the other orthologs will also turn out to have roles in hearing in mammals. Finally, the authors present the intriguing finding that two fly rhodopsins - rh5 and 6 - are expressed in the sensory cilium of the fly JO neurons and cause hearing defects when mutated. It will be extremely interesting to see if rhodopsins also play a role in vertebrate mechanotransduction. " -- Andy Groves (Faculty of 1000) "Must Read"
Binshtok AM, Bean BP, Woolf CJ. (2012) Inhibition of nociceptors by TRPV1-mediated entry of impermeant sodium channel blockers. Nature. 2007 Oct 4; 449(7162):607-10
"This exciting paper demonstrates a novel concept for pain relief.
This fascinating study shows that a membrane-impermeant anaesthetic, the lidocaine derivative QX-314, which blocks sodium channels only from inside, can enter the membrane of sensory neurons or sensory nerve fibres via the pore of the transient receptor potential channel, TRPV1, which is activated by capsaicin." --Bernd Nilius (Faculty of 1000) Exceptional.
Andersson, L.S., et al., Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice. Nature, 2012. 488(7413): p. 642-646.
A central pattern generator is a neural circuit responsible for generating a pattern of motor output. The spinal cord of vertebrates has CPGs responsible for the differing patterns of gait and other aspects of repetitive locomotion. In this study, a single gene mutation has an effect on locomotion by altering the neural network of both domestic horses and mice.
Liebeskind, BJ, Hillis, DM, and Zakon, HH. (2011) Evolution of sodium channels predates the origin of nervous systems in animals. PNAS 108 (22) 9154-9159.
The nervous system allows communication over long distances and permits multicellular organisms to get large and still coordinate cell activities and movement. Essential to the function of the nervous system is the ability to send signals rapidly - using propagated electrical impulses. In all animals with nervous systems, this property is dependent upon voltage gated sodium channels in nerve cell membranes. This makes neurons excitable, and nervous signal transmission rapid. This paper explores the evolution of sodium channels and surprisingly finds genes for sodium channels in the early ancestors of animals - the choanoflagellates.