Cellular/Molecular
Dendritic Protein Synthesis and CaMKII
Coleen M. Atkins, Naohito Nozaki, Yasushi Shigeri, and Thomas R. Soderling (see pages 5193–5201)
Synaptic plasticity in the hippocampus involves both an early phase dependent on phosphorylation of synaptic proteins and a late phase lasting hours to days that requires gene transcription and protein translation. A puzzling question has been how new proteins are targeted to potentiated synapses. The presence of certain mRNAs in dendrites, coupled with recent studies suggesting regulated translation at synapses by cytoplasmic polyadenylation element binding protein (CPEB), provide an intriguing possible mechanism. CPEB binds the 3′ untranslated region (UTR) of mRNA at a CPE-binding element to trigger polyadenylation and translation. In Xenopus oocytes and in neurons, CPEB can be regulated by the exotic-sounding Aurora kinase. Now, Atkins et al. show that CPEB is phosphorylated in neurons by calcium/calmodulin-dependent protein kinase II (CaMKII) in vitro and in postsynaptic density fractions. In transfected hippocampal neurons, depolarization induced translation of a luciferase protein fused to a 3′ UTR CPE-binding element. Thus not only is CaMKII mRNA present in dendrites, but CaMKII can also regulate dendritic protein synthesis.
Development/Plasticity/Repair
BDNF, Theta Bursts, and LTP
Enikö A. Kramár, Bin Lin, Ching-Yi Lin, Amy C. Arai, Christine M. Gall, and Gary Lynch (see pages 5151–5161)
Brain-derived neurotrophic factor (BDNF) has pleiotropic effects on gene expression and synaptic plasticity. In this week's Journal, Kramár et al. examined the mechanism underlying BDNF enhancement of long-term potentiation (LTP) induced by theta-burst stimulation. They identified small-conductance potassium (SK) channels as a downstream target. As in previous studies, BDNF treatment lowered the threshold for LTP induction and increased the maximal LTP elicited by theta bursts. Based on changes in the size and shape of individual bursts, the authors focused on the slow afterhyperpolarization (AHP) current that gradually declined over 30 min after BDNF infusion. The reduction in the AHP and the enhancement of LTP were mimicked by apamin and an SK2-specific peptide antagonist. Although immunoblots of hippocampal slices revealed that BDNF triggered serine phosphorylation of SK2 channels, a casual link between SK2 phosphorylation and the effects of BDNF on LTP awaits additional experiments.
Behavioral/Systems/Cognitive
Jumping, Kicking, and Scratching in the Frog
Corey B. Hart and Simon F. Giszter (see pages 5269–5282)
Frogs have characteristic motor repertoires, some of which are obvious to anyone that has walked close by a frog at the side of a pond. Likewise, isolated spinal cord preparations show characteristic rhythmic patterns and so-called “fictive” movements. How are more complex movements generated from these spinal patterns? This week, Hart and Giszter videotaped frogs in motion while recording electromyograms (EMGs) of hindlimb muscles to break down the movements into modules or spinal circuits. Brainstem and spinalized frogs had six common, multimuscle “drives” that were activated by pulses or bursts lasting ∼300 msec. They extracted this information from EMG records using an analysis method called independent component analysis (ICA). The bursts in brainstem frogs were more frequent and of lower amplitude, consistent with activation of subsets of muscle groups in the spinal frogs. These data suggest that a simple modular motor organization at the spinal level can account for the richer motor program of frogs in motion.
Neurobiology of Disease
Absence Epilepsy in the Mouse: It's Not Just T-Current
Yi Zhang, Alexander P. Vilaythong, Daniel Yoshor, and Jeffrey L. Noebels (see pages 5239–5248)
Inseon Song, Daesoo Kim, Soonwook Choi, Minjeong Sun, Yeongin Kim, and Hee-Sup Shin (see pages 5249–5257)
Spike-wave discharges (SWD) in absence seizures involve oscillations in thalamocortical networks. Low-voltage-activated or T-type calcium channels promote oscillations in thalamocortical relay neurons and play a critical role in SWDs. Perhaps surprisingly, natural mutations in mouse high-voltage-activated calcium subunits can cause increased thalamic T-currents and SWDs. Two papers in this week's Journal add to the link between defects in synaptic transmission and a pattern of enhanced T-currents with SWDs. Zhang et al. report that mice lacking one copy of SNAP-25, a presynaptic protein involved in exocytosis, have enhanced T-currents and cortical SWDs. Song et al. examined a null mutation for the α1A pore-forming subunit of P/Q-type calcium channels. The mice also displayed increased T-currents, SWDs, and absence seizures. Crossing the latter mice with mice lacking the α1G T-type subunit eliminated T-currents and SWDs. Thus low-voltage-activated calcium channels do indeed underlie SWDs and absence seizures, but dysfunction in other synaptic proteins can unmask the absence epilepsy phenotype.
Bilateral EEG traces show spike-wave discharges in Coloboma mutant mice that are blocked by ethosuximide, an anticonvulsant used to treat absence epilepsy. See the article by Zhang et al. for details.
