Neurological disorders

ERK activation causes epilepsy by stimulating NMDA receptor activity Nateri, A. S. et al. EMBO J. 1 Nov 2007 (doi: 10.1038/sj.emboj.7601911)

In this study, conditional expression of constitutively active (ca) MEK1 (MAP/ERK kinase 1) in the mouse brain was found to trigger spontaneous epileptic seizures, indicating a role for ERK–MAPK signalling in the aetiology of this neurological disorder. caMEK1 increased the expression of NMDA receptor 2B (NR2B) in an ERK-dependent manner, and pharmacological inhibition of NR2B abrogated epilepsy in vivo. NR2B could hence be a new target for anti-epileptic drugs.

Neuroimaging

GABA concentrations in the human anterior cingulate cortex predict negative BOLD responses in fMRI Northoff, G. et al. Nature Neurosci. 4 Nov 2007 (doi:10.1038/nn2001)

The default-mode network consists of brain areas that show reduced blood-oxygen-level-dependent (BOLD) responses during the execution of tasks, compared to a resting state. Using functional MRI and magnetic resonance spectroscopy, the authors showed that the reduced BOLD response in the anterior cingulate cortex, which is part of the default network, correlated with resting GABA (γ-aminobutyric acid), but not glutamine, concentrations in this area. The findings suggest that negative BOLD responses, which presumably reflect reduced neural activity, result from increased inhibitory, rather than decreased excitatory, transmission.

Regeneration

Molecular basis for the nerve dependence of limb regeneration in an adult vertebrate Kumar, A., Godwin, J. W., Gates, P. B., Garza-Garcia, A. A. & Brockes, J. P. Science 318, 772–777 (2007).

Brockes and colleagues have shed new light on the mechanisms that orchestrate the regeneration of an amputated limb in salamanders by identifying a key growth factor for blastemal cells, newt AG (nAG). nAG is a ligand for Prod1, a membrane-anchored protein expressed in blastemal cells. It is expressed in Schwann cells following amputation and, at later timepoints, in the wound epidermis. Denervation abolished nAG expression and, importantly, local re-expression of nAG rescued limb regeneration. Whether a similar approach works in mammals is yet to be determined.

Auditory system

The origin of spontaneous activity in the developing auditory system Tritsch, N. X. et al. Nature 450, 50–56 (2007)

During the development of the auditory system the sensory receptors (inner hair cells) display spontaneous activity in the period before the onset of hearing. This study shows that ATP released by supporting cells in the cochlea causes the inner hair cells to depolarize and fire in synchrony with neighbouring inner hair cells. The activated hair cells trigger discrete bursts of action potentials in afferent auditory neurons. The ATP-induced spontaneous firing of hair cells disappears upon the onset of hearing. These findings highlight the role of non-sensory, supporting cells in the development of the auditory system.