1. Putting the Freeze on the Presynaptic Terminal
Léa Siksou, Philippe Rostaing, Jean-Pierre Lechaire, Thomas Boudier, Toshihisa Ohtsuka, Anna Fejtová, Hung-Teh Kao, Paul Greengard, Eckart D. Gundelfinger, Antoine Triller, and Serge Marty
This week, Siksou et al. give us some close-up views of the cytomatrix in presynaptic terminals. To catch synaptic vesicles and particularly their filamentous network in the act, the authors immobilized rodent CA1 hippocampal slices by high-pressure freezing. Cryosubstitution and embedding preserved the architecture of the protein network. Electron tomography images were then reconstructed for a three-dimensional view. Within presynaptic boutons, filaments connected synaptic vesicles (SVs) to one another, and longer filaments (30–60 nm) linked the network to active zones in the presynaptic plasma membrane. On average, each SV was connected to 1.5 other SVs. Synapsins have been considered to be the filaments that maintain SV in position at the active zone. However, in mice lacking three synapsins, SV position was unchanged, and filaments linking them together were still present despite a significant drop in SV number. Thus, the cytomatrix appears not to depend on the integrity of synapsins.
2. Early Glucocorticoids and Later Neuroprotection
Paola Casolini, Maria Rosaria Domenici, Carlo Cinque, Giovanni Sebastiano Alemà, Valentina Chiodi, Mariangela Galluzzo, Marco Musumeci, Jerome Mairesse, Anna Rita Zuena, atrizia Matteucci, Giuseppe Marano, tefania Maccari, Ferdinando Nicoletti, and Assia Catalani
This week, Casolini et al. show that maternal behavior during a pup’s neonatal life makes a long-lasting imprint on the hypothalamic-pituitary-adrenal (HPA) axis. Rat dams received water supplemented with corticosterone (CORT), a hormonal treatment intended to mimic mild stress. The dams displayed increased maternal care behaviors with their nursing pups during the first 3 weeks of life. Remarkably, the male pups were protected from brain ischemia as adults. In the CORT-nursed adult rats, stress led to a blunted response of the HPA axis as measured by plasma CORT levels. After transient global ischemia, CORT-nursed rats did not display the spatial learning deficits observed in control rats, and in fact kept up with sham-operated rats in a water maze. Ischemia nearly eliminated hippocampal CA1 neurons in control rats, but neuron loss was much less in CORT-nursed rats.
3. A BOLD Look at Columnar Resolution
Chan-Hong Moon, Mitsuhiro Fukuda, Sung-Hong Park, and Seong-Gi Kim
A lot of action in brain circuits happens below the millimeter level, the rough limit of conventional functional magnetic resonance imaging (fMRI) based on gradient-echo (GE) blood-oxygenation-level-dependent (BOLD) signals. This week, Moon et al. combined GE fMRI with other techniques to determine whether they could extract information about submillimeter structures, specifically cortical iso-orientation columns in anesthetized cats. Single-orientation stimulation evoked GE BOLD responses throughout the brain, particularly around large pial veins, which obscured orientation-specific activation. The orientation-nonspecific response was reduced by continuous stimulation and was further dampened using the spin-echo (SE) fMRI technique. In order to determine whether iso-orientation maps could be reliably detected with GE fMRI, the authors compared BOLD responses in areas of expected greater neural activation. Indeed, the iso-orientation maps from GE and SE BOLD fMRI matched well with maps based on cerebral blood volume measurements.
4. Aneuploidy in Normal and Alzheimer Brain
Birgit Mosch, Markus Morawski, Anja Mittag, Dominik Lenz, Attila Tarnok, and Thomas Arendt
In Alzheimer’s disease (AD), some neurons display aneuploidy; that is, they contain extra copies of chromosomes. This week, Mosch et al. asked whether this multiplicity results from mis-segregation of chromosomes in neural progenitor cells, or from cell cycle reactivation. The authors quantified DNA in single neurons in entorhinal cortex of normal and AD brains, using three techniques: slide-based cytometry, PCR amplification of alu repeats, and chromogenic in situ hybridization. Control cases were divided based on their expression of cyclin B1, a mitotic marker. In both normal and AD brains, a small population of neurons contained more DNA than the normal diploid content; some were even tetraploid. These cells did not express cyclin B1 and probably inherited their aneuploidy from progenitor cells. In AD brains, however, a larger separate population of tetraploid neurons expressed cyclin B1, indicating that they had reentered the cell cycle.