Neurobiology Select

Neuroimaging, the topic of this Neurobiology Select, continues to advance our understanding of brain function at both the molecular and systems levels. Recent reports include the use of two-photon microscopy to study crosstalk between neighboring dendritic spines, the differences in activity between cortical layers, and the effects of presynaptic glutamate release on neuromuscular junction development and cortical blood flow. Long-term potentiation (LTP) is a lasting increase in synaptic strength stimulated by repeated activation of neuronal synapses. Although the induction of LTP is constrained to the synapse being stimulated, neighboring synapses become sensitized, such that the strength of the input needed to induce LTP is lowered. Harvey et al. (2008) now provide evidence that the spread of Ras signaling is one means by which neighboring synapses sharing the same dendrite acquire this enhanced sensitivity. Ras is a small GTPase that is activated in dendritic spines by the local influx of Ca 2+ , which occurs following, for example, NMDA receptor activation. The authors transfected rat hippocampal slices with a fluorescence resonance energy transfer-based reporter construct to visualize Ras activity in live neurons using two-photon mi-croscopy. Following stimulation of single dendritic spines using two-photon pulses to release ''caged'' molecules of the neurotransmitter glutamate locally, they observed Ras activity spreading to neighboring synapses over a time course of a few minutes. The rate and distance of Ras diffusion correlated with the reported propensity of neighboring synapses to acquire enhanced sensitivity to LTP-inducing stimulation. Future work may identify additional diffusible signals that mediate synaptic crosstalk. If such factors can be identified, it will interesting to determine whether their diffusion is similar to that found by Harvey and coworkers for Ras, which spreads over a distance of 10 mm along the dendrite, or if there are signals that function over both shorter and greater distances. In the fruit fly Drosophila the ionotropic receptors activated by the neurotransmitter glutamate are heteromeric tetramers. Three of the four subunits are constant, whereas the fourth subunit in the glutamate-gated ion channel can be either GluRIIA or GluRIIB. The receptors that result from the inclusion of the two variable subunits have unique electrophysiological properties and have different effects on synaptic development. In recent work, Schmid et al. (2008) examined the composition of glu-tamate receptors in vivo during the maturation of postsynaptic densities at fly neuromuscular junctions. They show that glutamate receptor composition changes during development and appears to be regulated …