Cellular/Molecular
Ca2+ Influx into Perisynaptic Glia Reflects Synaptic Strength
Houssam Darabid, Danielle Arbour, and Richard Robitaille
(see pages 1297–1313)
During development, two axons often innervate the same target and compete for dominance, after which one axon—usually the weaker one—retracts. This occurs, for example, at immature neuromuscular junctions (NMJs). Glia that surround NMJs and other synapses influence synaptic activity in the mature nervous system, but their potential role in synaptic competition during development is relatively unexplored. Darabid et al. report that many dually innervated NMJs in mice were surrounded by single perisynaptic glia cells that responded to stimulation of either nerve with an increase in intracellular Ca2+. The size of Ca2+ responses reflected the relative strength of the two synapses: activation of stronger synapses induced greater Ca2+ influx. Differential responses were not simply a result of increased transmitter release at stronger synapses, however, because increasing transmitter release at weaker synapses did not significantly increase Ca2+ responses. Whether such differential responses signal perisynaptic glia to help shape synaptic competition, e.g., by further potentiating strong synapses or actively disengaging weaker ones, remains to be seen.
Perisynaptic glia (blue) surround presynaptic (green) and postsynaptic (red) portions of NMJs and exhibit Ca2+ elevation in response to synaptic activity. See the article by Darabid et al. for details.
Development/Plasticity/Repair
Entorhinal Inputs Induce Heterosynaptic Potentiation in CA1
Edward B. Han and Stephen F. Heinemann
(see pages 1314–1325)
Afferents from the entorhinal cortex synapse on distal apical dendrites of pyramidal neurons in stratum lacunosum moleculare (SLM) of hippocampal CA1. Because these synapses are far from the soma, their activation is usually insufficient to induce pyramidal cell spiking; instead, their primary function appears to be to modulate inputs from CA3, which terminate more proximally, in stratum radiatum (SR). Remarkably, Han and Heinemann found that stimulation of SLM afferents in mouse hippocampal slices slowly potentiated proximal synapses even though the latter were not activated and no postsynaptic spikes were elicited. In contrast, stimulation of SR afferents induced only homosynaptic potentiation. Unlike homosynaptic potentiation, heterosynaptic potentiation of SR synapses involved increases in both AMPA- and NMDA-receptor signaling, the latter resulting partly from insertion of GluN2B-containing receptors, which are normally downregulated in adults. Interestingly, heterosynaptic potentiation of SR synapses occluded potentiation induced by moderate SR stimulation, but enhanced potentiation produced by strong SR stimulation. Thus, entorhinal cortical activity can induce metaplasticity at CA3–CA1 synapses.
Systems/Circuits
Fast and Slow Inhibition Improves Spike Timing
Ruili Xie and Paul B. Manis
(see pages 1598–1614)
The cochlear nuclei contain several subtypes of projection neurons that are differentially tuned to encode different features of sound. In the ventral cochlear nucleus, for example, bushy cells are tuned to encode the fine temporal structure of sound, which varies on the order of tens of microseconds and is used to identify pitch and localize sounds, whereas T-stellate cells encode the sound envelope, which varies over milliseconds and is used to group sounds and decipher speech. The unique response patterns of bushy and T-stellate cells arise from multiple cellular and network properties, including—as shown by Xie and Manis—the time course of their responses to glycinergic inputs from cells in the dorsal cochlear nucleus. Specifically, the decay time of IPSCs in bushy cells was much slower than that in T-stellate cells. Computational models showed that only slow IPSCs improved temporal precision of bushy cells given repeated synaptic input, whereas T-stellate cells required fast inhibition to detect narrowband signals in complex acoustic environments.
Neurobiology of Disease
L-Type Ca2+ Channel Agonists Rescue Effects of Mutant TDP-43
Gary A.B. Armstrong and Pierre Drapeau
(see pages 1741–1752)
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease that primarily affects motor neurons. Like degenerating neurons in several other diseases, motor neurons in ALS patients have cytoplasmic inclusions containing protein aggregates, including the DNA/RNA binding protein TDP-43, which is involved in RNA processing. Mutations in the gene encoding TDP-43 cause a small fraction of ALS cases. Armstrong and Drapeau examined the early pathological effects of human mutant TDP-43 by expressing it in zebrafish. Larval zebrafish expressing mutant TDP-43 swam more slowly and for shorter durations than controls, and communication between motor neurons and muscles was impaired in mutant fish: action potentials produced smaller, more variable endplate currents, with a lower success rate than normal. Furthermore, mutant fish had many postsynaptic acetylcholine receptor clusters that were not apposed to presynaptic protein clusters, and vice versa. Interestingly, all these effects were rescued by treating fish with L-type calcium channel agonists, which potentiated calcium influx into motor neuron terminals.
