Cellular/Molecular
Slow, Stop-and-Go Axonal Traffic
Subhojit Roy, Matthew J. Winton, Mark M. Black, John Q. Trojanowski, and Virginia M.-Y. Lee
(see pages 3131–3138)
This week, Roy et al. monitored traffic in the fast and slow lanes of axons. Proteins are transported to distal axons in three distinct groups: fast component (FC), slow component-a (SCa), and slow component-b (SCb). The well described FC and SCa mechanisms move vesicular and structural cargoes, respectively, to axons at vastly different speeds. SCb hauls loads such as proteins involved in axon growth at about 2–10 times the speed of SCa. The authors visualized SCb transport in live hippocampal neurons transfected with combinations of three fluorescently tagged SCb proteins: α-synuclein, synapsin-I, and glyceraldehyde-3-phosphate dehydrogenase, as well as the FC protein synaptophysin. A direct comparison of α-synuclein and synaptophysin transport revealed that SCb transport was much slower overall, but it had a herkyjerky quality, and its instantaneous velocity was surprisingly comparable with FC. Like SCa transport, the stop-and-go movement of the multiprotein SCb complexes slows traffic.
Development/Plasticity/Repair
Maternal Separation and Gene Expression in Monkeys
Michael J. Sabatini, Philip Ebert, David A. Lewis, Pat Levitt, Judy L. Cameron, and Károly Mirnics
(see pages 3295–3304)
Even most dads will admit there's nothing quite like mom when you are young. In this week's Journal, Sabatini et al. investigated the neural substrate of behaviors caused by maternal separation of monkeys at either 1 week or 1 month of age. Using DNA microarrays, the authors identified a single gene that was differentially regulated in 1 week and 1 month separation animals: the nitric oxide signaling molecule GUCY1A3, an analog of rat guanylate cyclase 1 α 1. In maternally reared control monkeys, in situ hybridization showed that GUCY1A3 was expressed at highest levels in the amygdala, and was expressed maximally by 1 week of age. Expression was significantly lower in 1 week maternally separated animals and was intermediate in 1 month separated monkeys. GUCY1A3 expression correlated with acute and long-term self- and social-comforting behaviors. Whether GUCY1A3 is simply a marker of this behavior or plays a causal role remains to be determined.
Behavioral/Systems/Cognitive
Input Fluctuations in Layer 5 Pyramidal Neurons
Maura Arsiero, Hans-Rudolf Lüscher, Brian Nils Lundstrom, and Michele Giugliano
(see pages 3274–3284)
Cortical neurons fire asynchronously, thus producing membrane voltage fluctuations in the synaptic potentials in downstream neurons. This week, Arsiero et al. asked how important these membrane fluctuations are to information processing. They recorded from layer 5 pyramidal neurons of rat medial prefrontal cortex (mPFC) in vitro. Using a fluctuating stimulus during voltage recording, the authors simulated input from a population of neurons and measured the mean firing rate response from single neurons. The mPFC neurons displayed a sigmoidal increase in firing rate with a maximal frequency of ∼40–60 Hz. The neurons remained highly sensitive to input current fluctuations, suggesting that they can encode irregular inputs, not just integrate the mean input. The authors suggest that the adaptation to input mean, but not to the variance, may be explained by slow voltage-dependent inactivation of the sodium current. Seems these neurons can stay on task even in a noisy environment.
Neurobiology of Disease
Minocycline, Microglia, and Amyloidosis
Rong Fan, Feng Xu, Mary Lou Previti, Judianne Davis, Alicia M. Grande, John K. Robinson, and William E. Van Nostrand
(see pages 3057–3063)
Amyloid-β(Aβ) can accumulate not only as parenchymal plaques in brain, but also as fibrillary deposits in cerebral vasculature. Early and severe vascular deposits in cerebral amyloid angiopathy (CAA) result from inherited Aβ mutations and are associated with a strong local neuroinflammatory reaction. The latter seems to correlate with amyloid extending from vessels into brain parenchyma. This week, Fan et al. measured the effects of a neural anti-inflammatory drug in Tg-SwDI mice. Decoding the name, the mouse is a transgenic strain that expresses human amyloid precursor protein carrying the Dutch- and Iowa-type familial CAA mutations. The anti-inflammatory drug minocycline did not affect fibrillar amyloid deposits in the microvasculature of Tg- SwDI mice, nor was total soluble or insoluble Aβ reduced. Minocycline also did not alter the number of reactive astrocytes. However, minocycline did reduce the number and activation state of microglia. After 4 weeks of treatment, 1-yearold mice displayed improved learning memory performance in a maze task.
Amyloid was deposited in cerebral vessels of Tg-SwDI mice at 1 year of age. Vascular collagen IV immunoreactivity (red) colocalized with staining for amyloid (thioflavin-S; green). See the article by Fan et al. for details.
