This Week in The Journal

Cellular/Molecular

Various Activity Patterns Occur during Slow Oscillations

Babak Tahvildari, Markus Wölfel, Alvaro Duque, and David A. McCormick

Slow-wave sleep is characterized by slow oscillations between “Up” states, in which cortical neurons receive barrages of synaptic input and fire action potentials, and “Down” states, during which neurons are relatively silent. Similar oscillations can be recorded in cortical slices in vitro. Up states are thought to be produced by recurrent excitatory and inhibitory networks involving pyramidal cells and fast-spiking GABAergic interneurons, but the role of other GABAergic neurons is unclear. To address this, Tahvildari et al. performed whole-cell recordings in mouse entorhinal slices in which different subpopulations of GABAergic interneurons were labeled. Pyramidal cells and fast-spiking interneurons were highly active during Up states, consistent with a predominant role of these neurons in maintaining persistent activity. Other neuron types rarely spiked during Up states. Depending on the cell type, lack of spiking was attributed to low input resistance, high spike threshold, stronger inhibitory than excitatory input, or minimal synaptic input.

Development/Plasticity/Repair

Reelin Signaling Shapes Development of Adult-Born Neurons

Catia M. Teixeira, Michelle M. Kron, Nuria Masachs, Helen Zhang, Diane C. Lagace, et al.

(see pages 12051–12065)

Reelin, an extracellular protein, regulates migration, lamination, axon guidance, and dendritic growth during cortical and hippocampal development. Reelin expression persists in the adult brain, where it regulates synaptogenesis and long-term potentiation. Teixeira et al. provide evidence that reelin signaling also influences differentiation, maturation, and incorporation of adult-born hippocampal neurons into circuits. Reelin exerts its effects via the adaptor protein Disabled-1 (Dab1). When Dab1 was deleted in neural progenitors in postnatal rodents, more glia and fewer dentate granule cells were generated than in controls. The neurons that were produced often migrated inappropriately to the hilus or the molecular layer. The dendrites of adult-born, Dab1-deficient neurons were shorter and less branched than controls, and many Dab1-deficient neurons extended dendrites into the hilus, something that normally does not occur. Hilar dendrites received synaptic inputs and Fos was activated in these neurons during seizures, suggesting that although abnormally orientated, the neurons became incorporated into functional circuits.

The dendrites of wild-type adult-born granule cells (top) extend through the granule cell layer (shaded area) into the molecular layer. Dendrites of Dab1-deficient neurons (bottom) are shorter than normal, and many are improperly oriented. See the article by Teixeira et al. for details.

Behavioral/Systems/Cognitive

Task-Associated Acetylcholine Release Induces Circadian Shift

Giovanna Paolone, Theresa M. Lee, and Martin Sarter

(see pages 12115–12128)

Performance on tasks requiring attention varies across the circadian cycle. Although rats' performance on such tasks is lowest during the day, their performance improves if they practice during short sessions every day. This improvement is associated with a shift to diurnal activity patterns that persist for several days after practice sessions stop. Motor tasks that do not require attention do not induce such shifts. Because increased attentional effort involves cholinergic input to the prefrontal cortex (PFC) and acetylcholine also regulates the sleep–wake cycle, Paolone et al. reasoned that task-induced increases in acetylcholine contributed to the circadian phase shift in rats. Remarkably, after termination of precisely timed practice sessions, PFC acetylcholine levels increased precisely at the time previous sessions had begun, and remained elevated until the time prior sessions had ended. Removing cholinergic inputs to the PFC impaired task performance and resulted in immediate reversion to nocturnal activity patterns after practice sessions ceased.

Neurobiology of Disease

Na⁺/Ca²⁺ Exchanger Plays Early Role in Axon Degeneration

Anna G. Barsukova, Michael Forte, and Dennis Bourdette

(see pages 12028–12037)

In many neurodegenerative diseases, axonal degeneration precedes cell death. Diverse insults—including genetic mutations, toxins, demyelination, and oxidative stress—induce a similar form of axonal degeneration. First, focal swellings appear along the axon. Proteins accumulate in these varicosities, causing them to grow into spheroids much larger than normal axon diameter. Meanwhile, intervening axonal segments narrow, sometimes to the point of severing. Finally, the axon distal to spheroids degenerates. To investigate the molecular underpinnings of axonal swelling, Barsukova et al. treated cultured cortical neurons from adult mice with H₂O₂, inducing oxidative damage. This caused abnormal accumulation of the Na⁺/Ca²⁺ exchanger and a voltage-gated Ca²⁺channel subunit at several points along the axon, leading to focal Ca²⁺ increases. Swellings subsequently developed at these sites. Progression of swellings to spheroids was associated with mitochondrial swelling and Ca²⁺ release. Blocking Ca²⁺ channels or the Na⁺/Ca²⁺ exchanger prevented axonal swelling, whereas blocking mitochondrial Ca²⁺ release prevented progression of swellings to spheroids.