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The Journal of Neuroscience, August 13, 2008, 28(33)

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This Week in The Journal
This Week in The Journal

Cellular/Molecular

Cav Shapes BK_Ca Kinetics

Henrike Berkefeld and Bernd Fakler

(see pages 8238–8245)

Large-conductance Ca²⁺- and voltage-activated potassium (BK_Ca) channels contribute to membrane repolarization after action potentials, shape dendritic spikes, and influence neurotransmitter release. Increasing intracellular calcium concentration shifts the activation potential of BK_Ca, which is essential for the channels to be activated at physiological voltages. A sufficient shift in activation potential occurs only when BK_Ca channels form complexes with voltage-activated calcium (Cav) channels. Now, Berkefeld and Fakler report that the onset and upward slope of BK_Ca activation—which varies widely across cell types—may largely be determined by which Cav channels the BK_Ca channels cluster with. When clustered with P/Q-type calcium channels (Cav2.1), BK_Ca activated at more hyperpolarized potentials and had a faster rise time than when clustered with L-type calcium channels (Cav1.2). The complexes also responded differently to simulated action potentials: action potentials with short duration reliably activated BK_Ca in BK_Ca–Cav2.1 complexes, whereas they often failed to activate BK_Ca in BK_Ca–Cav1.2 complexes.

Development/Plasticity/Repair

NF-B Phosphorylation State Determines Effect on Growth

Humberto Gutierrez, Gerard W. O'Keeffe, Núria Gavaldà, Denis Gallagher, and Alun M. Davies

(see pages 8246–8256)

The transcription factor nuclear factor B (NF-B) regulates many cellular functions, including neurite outgrowth from nodose ganglion neurons. Gutierrez et al. now report that NF-B stimulates or inhibits neurite growth depending on the phosphorylation state of one amino acid. Superior cervical ganglion sympathetic neurons and nodose sensory neurons were cultured from neonatal mice and then transfected with proteins that either increased or decreased NF-B-mediated transcription. In sympathetic neurons, NF-B signaling was unnecessary for neurite growth, but enhancing NF-B transcriptional activity inhibited neurite outgrowth. In sensory neurons, surprisingly, some treatments that enhanced NF-B function increased neurite outgrowth, and others decreased outgrowth. These effects were traced to the activity of a kinase that phosphorylates NF-B, which was constitutively active in sympathetic neurons. Eliminating the phosphorylation site on NF-B prevented inhibition of neurite growth, whereas mutating it to mimic constitutive phosphorylation inhibited neurite growth in both sensory and sympathetic neurons.

Behavioral/Systems/Cognitive

Reward Activates Primary Somatosensory Cortex

Burkhard Pleger, Felix Blankenburg, Christian C. Ruff, Jon Driver, and Raymond J. Dolan

(see pages 8161–8168)

Receiving a reward activates sensory cortex, which might improve future performance, according to Pleger et al. Human subjects discriminated the frequency of two electrical stimuli applied to a finger. Before stimulation, a visual cue indicated the amount of reward given for a correct discrimination. After the subjects' response, a visual signal indicated whether they received the anticipated reward (for correct discrimination) or no reward (for incorrect answers). Functional magnetic resonance imaging revealed that finger stimulation activated primary somatosensory cortex (SI) the same amount regardless of the size of the anticipated reward. Remarkably, however, SI was activated again by receipt of the reward, in proportion to the size of the reward. Moreover, after a reward was received, SI was more activated by stimulation on the next trial, and this effect was also larger for larger rewards. This reward-related activation, which was distinguishable from attention-related activation, was correlated with improved discrimination performance.

Neurobiology of Disease

Proteasome Dysfunction Causes Neurodegeneration

Lynn Bedford, David Hay, Anny Devoy, Simon Paine, Des G. Powe, Rashmi Seth, Trevor Gray, Ian Topham, Kevin Fone, Nooshin Rezvani, Maureen Mee, Tim Soane, Robert Layfield, Paul W. Sheppard, Ted Ebendal, Dmitry Usoskin, James Lowe, and R. John Mayer

(see pages 8189–8198)

The ubiquitin proteasome system helps maintain cellular function by limiting the lifespan of regulatory proteins and degrading defective proteins. The addition of polyubiquitin chains to such proteins targets them for degradation by the 26S proteasome complex. Accumulation of ubiquitinated proteins characterizes many neurodegenerative diseases, including Parkinson's disease, suggesting that dysfunction of the proteasome system is involved in these diseases. But direct tests of this hypothesis have produced controversial results. This week, Bedford et al. provide definitive evidence that loss of proteasome function causes neurodegeneration. They produced mice in which an essential component of the 26S proteasome complex was conditionally knocked out in forebrain or substantia nigra neurons. This greatly reduced the number of 26S proteasome complexes in the affected neurons without affecting ubiquitin-independent degradation. Ubiquitinated proteins accumulated in the neurons, forming inclusions like those seen in neurodegenerative diseases, and this ultimately led to neurodegeneration and apoptosis.

View larger version (103K): [in this window] [in a new window]   Neurons lacking an essential component of the 26S proteasome complex (top) accumulate ubiquitinated proteins (brown) much more than controls (bottom).

 

Related articles in J. Neurosci.:

Reward Facilitates Tactile Judgments and Modulates Hemodynamic Responses in Human Primary Somatosensory Cortex

Burkhard Pleger, Felix Blankenburg, Christian C. Ruff, Jon Driver, and Raymond J. Dolan
J. Neurosci. 2008 28: 8161-8168. [Abstract] [Full Text]  

Depletion of 26S Proteasomes in Mouse Brain Neurons Causes Neurodegeneration and Lewy-Like Inclusions Resembling Human Pale Bodies

Lynn Bedford, David Hay, Anny Devoy, Simon Paine, Des G. Powe, Rashmi Seth, Trevor Gray, Ian Topham, Kevin Fone, Nooshin Rezvani, Maureen Mee, Tim Soane, Robert Layfield, Paul W. Sheppard, Ted Ebendal, Dmitry Usoskin, James Lowe, and R. John Mayer
J. Neurosci. 2008 28: 8189-8198. [Abstract] [Full Text]  

Repolarizing Responses of BK_Ca–Cav Complexes Are Distinctly Shaped by Their Cav Subunits

Henrike Berkefeld and Bernd Fakler
J. Neurosci. 2008 28: 8238-8245. [Abstract] [Full Text]  

Nuclear Factor B Signaling Either Stimulates or Inhibits Neurite Growth Depending on the Phosphorylation Status of p65/RelA

Humberto Gutierrez, Gerard W. O'Keeffe, Núria Gavaldà, Denis Gallagher, and Alun M. Davies
J. Neurosci. 2008 28: 8246-8256. [Abstract] [Full Text]  

This Article Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Related articles in J. Neurosci. Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content

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