Cellular/Molecular
Making Dendritic Spikes
Sonia Gasparini, Michele Migliore, and Jeffrey C. Magee
(see pages 11046-11056)
Not so long ago, dendrites were considered passive conduits, not active, spike-generating compartments. We now know that in some neurons, action potentials can originate in dendrites and propagate to the soma, and these spikes can also backpropagate from the soma into dendrites. This week, Gasparini et al. examine the conditions required for distal spike generation using dendritic and somatic recording in CA1 pyramidal neurons. They used computer simulation to explore the factors regulating dendritic spikes. In dendrites, the action potential threshold was ∼10 mV more depolarized than at the soma, a property determined by the dendritic sodium and potassium channel density. To evoke dendritic spikes, synaptic inputs had to be clustered in time and space, within 100 μm and a few milliseconds. However, when they occurred, dendritic spikes triggered short-latency spike output in the axons. Thus with clustered incoming activity, dendritic spikes can provide more bang for the buck.
Development/Plasticity/Repair
Bax-Less Living in the Dentate Gyrus
Woong Sun, Adam Winseck, Sharon Vinsant, Ok-hee Park, Hyun Kim, and Ronald W. Oppenheim
(see pages 11205-11213)
Making it in the adult world can be tough. Although new neurons are continuously produced in the dentate gyrus of the hippocampus throughout life, programmed cell death kills off 60-80%. The Bcl-2 family proapoptotic protein Bax has been implicated in this cell death. This week, Sun et al. examine the impact of Bax on neuronal paring in the adult. Unlike wild-type mice, adult mice lacking Bax showed no evidence of apoptosis in the subgranular zone of the dentate gyrus, whereas the size of the dentate gyrus increased. Markers of mature granule cells such as neuronal-specific nuclear protein (NeuN) confirmed an increase in mature neurons. Bromodeoxyuridine labeling showed that cell proliferation remained intact, consistent with an effect of Bax on cell death, not production of new cells. Granule cell migration was also disrupted in mice lacking Bax, perhaps a confirmation that more neurons are not necessarily better.
Behavioral/Systems/Cognitive
Wake-Sleep Cycling in the Rat
Damien Gervasoni, Shih-Chieh Lin, Sidarta Ribeiro, Ernesto S. Soares, Janaina Pantoja, and Miguel A. L. Nicolelis
(see pages 11137-11147)
Just as behavior differs greatly between waking and sleep states, so too does electrical brain activity, from the fast oscillating pattern of wakefulness to the slower waves of sleep states and then back to the fast activity associated with rapid eye movement (REM) sleep. This week, Gervasoni et al. examine the dynamics of the wake-sleep cycle. They classified rat behavior into five states and created state maps by recording local field potentials (LFPs) in several forebrain areas: cortex, hippocampus, thalamus, and striatum. The LFPs were tightly correlated with the behavioral states and several substates. Remarkably, the transitions between states occurred simultaneously throughout remote areas of the forebrain, indicating a high degree of functional integration across time and space. The authors postulate that the transient oscillatory synchronization of synaptic inputs that drive the state transitions may facilitate information exchange between different brain areas.
Neurobiology of Disease
Insulin, IDE, and β-Amyloid
Lixia Zhao, Bruce Teter, Takashi Morihara, Giselle P. Lim, Surendra S. Ambegaokar, Oliver J. Ubeda, Sally A. Frautschy, and Greg M. Cole
(see pages 11120-11126)
Insulin-degrading enzyme (IDE), despite its name, can also degrade β-amyloid (Aβ) peptide that accumulates in Alzheimer's disease (AD). There are some tantalizing clues linking IDE and AD. For example, IDE is decreased in AD brain tissue, and genetic linkage studies implicate chromosome 10q in AD, the area where the IDE gene resides. This evidence has prompted some to suggest that IDE upregulation could be a therapeutic strategy in AD. This week Zhao et al. examine several aspects of this idea. With insulin treatment, cultured hippocampal neurons upregulated IDE, apparently through phosphatidylinositol-3 (PI3) kinase activation. In the hippocampus and cortex of human AD brains, the authors found reduced levels of both IDE and the P85 subunit of PI3. Finally, they examined an animal model of AD, the Tg2576 Swedish amyloid precursor protein mutant mouse. After a high-fat diet to exacerbate pathogenesis, the mutant mice expressed lower levels of IDE and increased Aβ monomers.
Intracranial LFPs during five brain behavioral states. Cx, Somatosensory cortex; Hi, hippocampus; CP, caudate-putamen; Th, thalamus. See the article by Gervasoni et al. for details.
