Cellular/Molecular
Calcium Signals across a Large Active Zone
Elliot S. Wachman, Robert E. Poage, Daniel L. Farkas, and Stephen D. Meriney (see pages 2877–2885)
Calcium entry into nerve terminals is generally considered one of the most reliable aspects of synaptic transmission, although the probability of transmitter release at excitatory synapses often is low. Because high concentrations of calcium are required for release, free calcium must be high at active zones. However, the small size of most active zones has made it difficult to assess calcium levels at subactive zone resolution. This week, Wachman et al., taking advantage of the large size of frog neuromuscular junction (NMJ) active zones, took 1 msec snapshots of calcium influx across the active zone. Blocking some of the N-type calcium channels with ω-conotoxin reduced the number but not the intensity of calcium transients detected by Calcium Green-1. The authors conclude that only very few or perhaps even single calcium channels mediate calcium entry at the 30 or so release sites within an active zone, and that calcium channels at this synapse have a low probability of opening. It seems that, at least for the NMJ, you can make a highly reliable synapse if you use enough unreliable components.
Development/Plasticity/Repair
Phenotypes of Hippocampal and Hypothalamic Progenitors
Eleni A. Markakis, Theo D. Palmer, Lynne Randolph-Moore, Pasko Rakic, and Fred H. Gage (see pages 2886–2897)
The dentate gyrus and the subependymal zone continue to produce newborn neurons in the adult mammalian brain. Progenitor cells in these regions generate well defined cell populations, dentate granule cells and interneurons destined for the olfactory bulb, respectively. However progenitors isolated and cultured from these regions show a broad range of transmitter phenotypes. To understand the subtypes that can be derived from progenitors in young adult rats, Markakis et al. compared neural progenitor cultures from the hippocampus with those from the hypothalamus, a region that ordinarily does not support adult neurogenesis. They categorized cells based on the presence of neuroendocrine peptides: cells usually present in both tissues, those present only in the hypothalamus, and gonadotropin-releasing hormone (GnRH) cells that originate in the olfactory placode and then migrate into the hypothalamus. Both progenitor cultures generated neurons and glia. All three categories were present in both cultures, indicating that progenitors in culture are indeed multipotent and can develop into phenotypes that are usually inhibited in vivo by the microenvironment.
Behavioral/Systems/Cognitive
Fear and Smiling in the Amygdala
Mark A. Williams, Adam P. Morris, Francis McGlone, David F. Abbott, and Jason B. Mattingley (see pages 2898–2904)
The human amygdala processes signs of impending danger, such as a fearful or angry face. Separate cortical and subcortical pathways may transmit these visual signals, an idea that Williams et al. explore this week using functional magnetic resonance imaging. They tapped the phenomenon of binocular rivalry, in which a different image is presented to each eye, and one image is suppressed at any given moment. In these studies, for presentations of <1 sec, only the dominant image was perceived; the other was suppressed. A fearful, happy or neutral face was presented to one eye, while an image of a house competed for dominance. As expected, the amygdala responded to even a suppressed fearful face image. Interestingly, the amygdala also responded to a happy face, but only when that image was suppressed. The authors suggest that a subcortical pathway functions as an early warning system, albeit somewhat unreliably, whereas the cortical pathway is slower but more precise. Better safe than sorry it seems.
Neurobiology of Disease
Molecular Fingerprints of Post-Traumatic Apoptosis
Paolo G. Marciano, Julia Brettschneider, Elisabetta Manduchi, Jason E. Davis, Scott Eastman, Ramesh Raghupathi, Kathryn E. Saatman, Terence P. Speed, Christian J. Stoeckert Jr, James H. Eberwine, and Tracy K. McIntosh (see pages 2866–2876)
Traumatic brain injury (TBI) can point neurons down the path toward apoptotic death in vulnerable areas such as the hippocampus. Caspase activation is one of the early steps, but other gene cascades are activated as well. Now Marciano et al. take inventory of gene expression profiles in individual pyramidal and granule neurons of CA3 and dentate gyrus in the controlled cortical impact (CCI) model of TBI. Neurons were classified as uninjured, caspase-3-activated, or committed to apoptosis [terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL)-positive]. The authors designed microarrays that randomly sampled the entire genome. Uninjured cells transcribed 59% of the mRNAs on the array, but injury caused a dramatic rise in mRNA levels, presumably encoding immediate early genes and other signaling cascade genes. Gene expression dropped drastically in TUNEL-positive neurons. The specific genes activated or downregulated with CCI diverged with cell morphology and location, suggesting cell-type specificity of the apoptotic response.
Single-cell microdissection of a hippocampal neuron for mRNA amplification and subsequent analysis by microarrays. See the article by Marciano et al. for details.
