Cellular/Molecular
Spines Rich in PSD-95 Can Retract
Georgia F. Woods, Won Chan Oh, Lauren C. Boudewyn, Sarah K. Mikula, and Karen Zito
(see pages 12129–12138)
The postsynaptic density protein PSD-95 creates a scaffold for organizing receptors, ion channels, cytoskeletal proteins, adhesion molecules, and signaling molecules at glutamatergic synapses. As such, PSD-95 plays a central role in determining postsynaptic density size and helps regulate synaptic strength. PSD-95 is thought to be an important component of synaptic plasticity, because its overexpression increases synaptic glutamate receptor levels, EPSC amplitude, and spine density. Given these roles, Woods et al. hypothesized that reduction of PSD-95 would be necessary during destabilization and elimination of dendritic spines. Consistent with this hypothesis, time-lapse two-photon microscopy revealed that most dendritic spines that retracted within a 1 h recording session in rat hippocampal slice cultures had relatively low levels of PSD-95. Nonetheless, some spines that retracted had relatively high levels of PSD-95, and levels remained high during retraction. Thus, high PSD-95 expression does not guarantee spine retention, and loss of PSD-95 is not a prerequisite for spine elimination.
Development/Plasticity/Repair
p38 Triggers Cholinergic Switch in Sympathetic Neurons
Bernhard Loy, Galina Apostolova, Roland Dorn, Victoria A. McGuire, J. Simon C. Arthur, et al.
(see pages 12059–12067)
Sympathetic neurons are noradrenergic when they first differentiate. Some of these neurons, specifically those that innervate sweat glands, subsequently transdifferentiate into cholinergic neurons in response to target-derived cytokines. These cytokines act on gp130/LIFRβ heterodimeric receptors, leading via poorly defined signaling cascades to activation of the nuclear matrix protein Satb2, which drives expression of cholinergic genes. Loy et al. discovered that p38 mitogen-activated protein kinase—a kinase normally associated with cell stress pathways and apoptosis—is required for this cholinergic switch. Treatment of cultured rodent noradrenergic sympathetic neurons with ciliary neurotrophic factor (CNTF) or leukemia inhibitory factor (LIF), both of which cause transdifferentiation, led to rapid and sustained activation of p38. Overexpression of p38 caused upregulation of cholinergic markers, whereas p38 inhibitors prevented CNTF- and LIF-induced upregulation of Satb2 and cholinergic markers. In addition, mice lacking p38β had fewer cholinergic neurons than control mice in the ganglion that innervates sweat glands.
Spines that have relatively high levels of PSD-95 (blue circle, left) can retract (right). See the article by Woods et al. for details.
Behavioral/Systems/Cognitive
Subiculum Generates Fast and Slow Gamma Rhythms
Jesse Jackson, Romain Goutagny, and Sylvain Williams
(see pages 12104–12117)
Local field potentials (LFPs) within many brain areas oscillate at multiple frequencies. Oscillations at gamma frequencies (∼30–140 Hz) depend on local inhibitory connections and are thought to be important for synchronizing ensembles of principal neurons to facilitate and temporally organize information transfer. Two distinct gamma frequency bands are present within the hippocampal formation: slow (25–50 Hz), which originates in CA3, and fast (80–140 Hz), which originates in medial entorhinal cortex (MEC). CA3 and MEC transmit gamma oscillations to distinct subsets of CA1 neurons at different times, depending on whether information is being encoded or retrieved. Because CA1 and MEC project to the subiculum, Jackson et al. expected to find both slow and fast oscillations in this structure. Indeed, both frequencies were present in rat subiculum in vitro, but unexpectedly, these oscillations were generated within the subiculum itself. Unlike in CA1, both frequencies sometimes occurred simultaneously in subiculum, and neurons could phase-lock to either frequency.
Neurobiology of Disease
Sympathetic Outflow Is Not Resistant to Leptin in Obese Mice
Pablo J. Enriori, Puspha Sinnayah, Stephanie E. Simonds, Cecilia Garcia Rudaz, and Michael A. Cowley
(see pages 12189–12197)
Unlike the more familiar white fat tissue, brown adipose tissue (BAT) does not function in lipid storage, but rather in thermogenesis. Sympathetic stimulation of brown adipocytes leads to activation of uncoupling protein 1, which allows the electrochemical gradient across inner mitochondrial membranes to dissipate without producing ATP; instead, heat is produced. This process allows small mammals to survive in cold climates, and it helps to maintain energy balance by boosting energy consumption when caloric intake is high. Hypothalamic nuclei involved in energy balance respond to leptin, a hormone present in blood at levels proportional to body fat. Increased leptin levels decrease appetite and increase sympathetic outflow to BAT, stimulating thermogenesis. If consumption of high-calorie foods continues, however, rodents become resistant to leptin, which no longer reduces appetite. Nonetheless, Enriori et al. found that leptin retained its ability to induce BAT thermogenesis in these mice. Thermogenesis raised body temperature, but did not consume sufficient energy to prevent obesity.
