Cellular/Molecular
Asynchronous Transmitter Release at Excitatory Synapses
Yo Otsu, Vahid Shahrezaei, Bo Li, Lynn A. Raymond, Kerry R. Delaney, and Timothy H. Murphy
(see pages 420-433)
The spontaneous quantal release of neurotransmitter, “minis,” may turn out to be more important than just a handy tool for quantitatively minded neurophysiologists. This week Otsu et al. report competition between phasic (evoked) release and asynchronous (spontaneous) release at hippocampal autapses in culture. Trains of stimuli depleted the readily releasable pool (RRP) of vesicles, resulting in depression of phasic release, yet synchronous release continued at a high rate. Asynchronous release also was unaffected by sucrose-induced depletion of the RRP. In contrast, blocking asynchronous release by reducing basal cytoplasmic calcium levels actually enhanced evoked release. Although both modes appear to share a common vesicle pool, recovery of asynchronous release after RRP depletion may be limited only by vesicle refilling while at the same time requiring a lower level of “bulk” intraterminal calcium. The authors suggest that under some circumstances, synapses may be able to maintain transmission at near maximal rates by using asynchronous release as a backup mechanism.
EPSC induced by phasic and asynchronous release during 20 Hz stimulation. See the article by Otsu et al. for details.
Development/Plasticity/Repair
CaMKIV and Cortical Plasticity
Jasmin Lalonde, Pascal E. D. Lachance, and Avi Chaudhuri
(see pages 554-564)
CaMKIV expression in cell nuclei can contribute to neuroprotection and adaptive plasticity by activating CREB-dependent gene expression. This week, Lalonde et al. examined the pattern of CaMKIV expression in monkey visual cortex (V1). In infants, kinase immunoreactivity was high in nuclei of interneurons, whereas in adults the expression was primarily cytoplasmic. Prolonged monocular deprivation did not affect the CaMKIV expression pattern in infants, but nuclear kinase gradually increased in adults, apparently because of translocation from the cytoplasm. Expression overlapped with certain interneuronal markers such as parvalbumin (e.g., chandelier cells) and calretinin (e.g., Cajal-Retzius cells), suggesting that kinase translocation occurred primarily in interneurons with horizontal connectivity between columns. Although high expression of CaMKIV during developmental plasticity might be expected, the spatial and temporal pattern of CaMKIV expression in the adult may provide clues to the residual plasticity in the adult neocortex.
Behavioral/Systems/Cognitive
A Mechanism for Vocal Learning in Songbirds
Long Ding and David J. Perkel
(see pages 488-494)
Fathers get to act as tutors for young songbirds as they learn their signature song that persists into adulthood. Although the neural pathways of the so-called song system are well mapped, the cellular mechanisms underlying this neural plasticity are less clearly understood. Now Ding and Perkel describe a Hebbian long-term potentiation (LTP) that seems to fit the bill. They examined activity-dependent synaptic potentiation in spiny neurons of area X, a basal ganglia nucleus that receives glutamatergic input from the higher vocal center (HVC) and dopaminergic input from the ventral tegmental area (VTA). The potentiation required activation of both NMDA and D1 receptors and could be induced only in finches that were >47 d old, an age that correlates with the transition from the sensory learning to the practice phase of song learning. The authors also point out an intriguing correlation between the age of LTP expression and the innervation of area X by dopaminergic neurons from the VTA.
Neurobiology of Disease
Implicating Astrocytes in β-Amyloid Toxicity
Andrey Y. Abramov, Laura Canevari, and Michael R. Duchen
(see pages 565-575)
Alzheimer's disease (AD) is marked by accumulation of β-amyloid (βA)-containing plaques. Although the role of βA as a diagnostic feature is clearly established, the mechanisms underlying the neurotoxicity of βA are less clear. While AD is usually thought of as a disease of neurons, Abramov et al. report that in neuron-astrocyte cultures, βA induced a collapse of the mitochondrial membrane potential in astrocytes. Astrocyte mitochondrial responses to βA showed several patterns: rapid depolarizations associated with cytoplasmic calcium increases as well as a slow collapse of the mitochondrial potential developing over several minutes. The latter was prevented by antioxidants and by glutamate acting as a metabolic substrate. The authors suggest that the collapse arises from oxidative stress on the metabolic enzymes that provide energy for mitochondrial respiration. They tracked the reactive oxygen species (ROS) to NADPH oxidase. The authors suggest that astrocyte injury may secondarily lead to βA-induced neuronal death.
