This Week in The Journal
H-ras Signaling and Synaptic Plasticity
Steven A. Kushner, Ype Elgersma, Geoffrey G. Murphy, Dick Jaarsma, Geeske M. van Woerden, Mohammad Reza Hojjati, Yijun Cui, Janelle C. LeBoutillier, Diano F. Marrone, Esther S. Choi, Chris I. De Zeeuw, Ted L. Petit, Lucas Pozzo-Miller, and Alcino J. Silva
(see pages 9721-9734)
In presynaptic terminals, synapsin I tethers synaptic vesicles to the actin cytoskeleton. This interaction has long been considered a target for synaptic plasticity given that phosphorylation alters the affinity of synapsin I for its binding partners. This week, Kushner et al. explore the role of H-ras/extracellular signal-regulated kinase (ERK) signaling in synapsin I phosphorylation and synaptic plasticity. In wild-type mice, synapsin I was phosphorylated during contextual fear conditioning. Transgenic mice with a constitutively active mutant H-ras, a potent activator of ERK, showed increased synapsin I phosphorylation as well as an increased number of docked vesicles. An increase in miniature EPSCs and paired-pulse facilitation were also observed, consistent with enhanced presynaptic function. Endogenous H-ras as well as the mutant form were predominately expressed in presynaptic axon terminals in the hippocampus of mature animals. The frequency-dependent increase in presynaptic release also led to enhanced induction of long-term potentiation in mutant H-ras mice.
Owls on the Prowl
Joseph F. Bergan, Peter Ro, Daniel Ro, and Eric I. Knudsen
(see pages 9816-9820)
The eyes and ears of the barn owl provide a formidable adversary for the barn mouse. To examine this elegant system, the precise alignment of topographical maps of visual and auditory space in the optic tectum can be perturbed with prism-containing goggles. Juvenile owls readily adapt their auditory maps under these conditions, but adults show much less plasticity. This week, Bergan et al. tested whether hunting live prey would enhance adult plasticity. Goggled adult owls hunted 1 h each day. The hunt was conducted in "moonlight" with one mouse at a time released into an aviary in which the floor was covered with shredded paper, allowing the owls to hear the rustling. Hunting enhanced the realignment of the auditory map as manifested by shifts in the tuning of the interaural timing difference. Perhaps of more interest to the owl community, the live action also improved hunting performance.
CCK-Expressing Interneurons and Hippocampal Oscillations
Thomas Klausberger, Laszlo F. Marton, Joseph O'Neill, Jojanneke H. J. Huck, Yannis Dalezios, Pablo Fuentealba, Wai Yee Suen, Edit Papp, Takeshi Kaneko, Masahiko Watanabe, Jozsef Csicsvari, and Peter Somogyi
(see pages 9782-9793)
GABAergic interneurons in the hippocampus modulate the timing of network oscillations. For example, parvalbumin (PV)-containing interneurons, which innervate different subcellular domains of CA1 pyramidal cells, show distinct firing patterns during theta (4-10 Hz) and ripple (120-200 Hz) oscillations. In this week's Journal, Klausberger et al. examined the in vivo firing properties of another class of interneurons, those expressing cholecystokinin (CCK). Of a total of 36 interneurons tested, nine cells were labeled with CCK. Like PV cells, CCK cells targeted the soma and dendrites of pyramidal cells. Unlike PV cells, some CCK cells expressed vasoactive intestinal polypeptide, cannabinoid receptor type 1, and vesicular glutamate transporter type 3. CCK cells also differed from PV cells in their firing patterns. CCK cells showed high-frequency firing during the ascending phase of theta oscillations. The average firing of CCK cells was not correlated with ripple episodes, but the authors found evidence of changes in firing during ripple episodes.
Neurobiology of DiseaseSilencing Mutant Huntingtin Late in the Course
Miguel Díaz-Hernández, Jesús Torres-Peraza, Alejandro Salvatori-Abarca, María A. Morán, Pilar Gómez-Ramos, Jordi Alberch, and José J. Lucas
(see pages 9773-9781)
This week, Díaz-Hernández et al. try to arrest Huntington's disease (HD) late in the course by silencing mutant huntingtin (htt) in a mouse model of HD (Tet/HD94). Despite progressive loss of motor coordination, striatal atrophy, and neuronal htt-positive inclusions, the Tet/HD94 mice do not show loss of striatal neurons until 17 months of age. At this late stage, the authors treated the conditional mutant mice with doxycycline to shut off expression of the htt transgene. After five additional months, "gene-off" mice showed improved motor performance, whereas untreated "gene-on" Tet/HD94 mice continued to worsen. Although their motor performance was the same as control mice, the gene-off Tet/HD94 mice did show a 20% loss of striatal neurons at 22 months, albeit less than the >40% cell loss in gene-on mice. The authors suggest that gene silencing even at a late stage could have therapeutic potential.