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The Journal of Neuroscience, October 29, 2003, 23(30)
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This Week in the Journal
Cellular/Molecular
Calcium, Adenylyl Cyclases, and Mossy Fiber LTP
Type 8 Adenylyl Cyclase Is Targeted to Excitatory Synapses and Required for Mossy Fiber Long-Term Potentiation
Hongbing Wang, Victor V. Pineda, Guy C. K. Chan, Scott T. Wong, Louis J. Muglia, and Daniel R. Storm (see pages 9710–9718)
Long-term potentiation (LTP) at the mossy fiber/CA3 pathway in the hippocampus depends on presynaptic increases in cAMP. Although there are multiple adenylyl cyclases, only two, AC1 and AC8, are calcium/calmodulin-dependent and expressed in the hippocampus. AC1–/– mice were shown previously to have reduced mossy fiber LTP. Now Wang et al. have created AC8 and AC1 x AC8 double knock-out (DKO) mice to examine the role of AC8 in this form of synaptic plasticity. AC8 accounts for only 20% of calcium-stimulated hippocampal adenylyl cyclase activity and is much less sensitive to calcium, requiring nearly 1 µM calcium for half-maximal stimulation. Nonetheless, AC8–/– and DKO mice showed a loss of LTP similar to AC1–/– mice. Of note, LTP was not eliminated in the DKO mice, suggesting that a component of this form of plasticity is independent of calcium-stimulated adenylyl cyclases. The apparent overlapping roles for the two enzymes may be explained by differences in localization: hemagglutinintagged AC8 colocalized with excitatory synaptic markers, whereas the punctate staining of AC1 was located 1–2 µm away from synapses. The authors also point out that the two enzymes also can be differentially regulated, because Gs-coupled receptors can act synergistically with calcium to stimulate AC1 but not AC8.
Development/Plasticity/Repair
Cueing Pioneer Axons with a Cadherin
R-Cadherin Is a Pax6-Regulated, Growth-Promoting Cue for Pioneer Axons
Gracie L. Andrews and Grant S. Mastick (see pages 9873–9880)
Pioneer axons form organized tracts that serve as roadways for neuronal development. The first longitudinal pioneers form the tract of the postoptic commissure (TPOC). Attractive and repulsive signals guide commissural axons, but the factors that guide longitudinal pioneer axons are less clear. One idea is that homophilic interactions between adhesion molecules, expressed by axons and their substrates, guide growth. This week, Andrews and Mastick examine the guidance properties of the adhesion molecule R-cadherin (Rcad) in TPOC axons and try to establish a link with the transcription factor Pax6. Normally, TPOC axons follow a path of Rcad expression through the ventral thalamus (VT) but then cross into the R-cadherin-deficient dorsal thalamus (DT). However, TPOC axons in Pax6 knock-out mice exhibited severe path-finding errors in the VT and failed to cross into the DT, suggesting that Pax6 may serve to control brain patterning through Rcad as well as other Rcad-independent guidance cues.
Behavioral/Systems/Cognitive
Motivating Dopamine Neurons
Correlated Coding of Motivation and Outcome of Decision by Dopamine Neurons
Takemasa Satoh, Sadamu Nakai, Tatsuo Sato, and Minoru Kimura (see pages 9913–9923)
In this week's Journal, Kimura et al. take a look at longstanding theories of reward-based learning by observing the activity of individual midbrain dopaminergic (DAergic) neurons in the reward pathway of the monkey. The output of these dopamine neurons has been correlated previously with the delivery of an expected reward to conditioned stimuli such that activity increases with an unexpected reward, decreases if a reward is withheld, and remains constant if the reward is as expected. Here, the authors devised a learning and reward task in which monkeys were given a choice of three buttons, one of which delivered a reward. They were allowed to continue pressing buttons until the correct choice was found; accordingly, the expectation for reward went up with each button push. The monkeys were trained for several months during which their reward expectations changed. Interestingly, DA neuronal activity was correlated not only with reward expectation errors, representing the assumed role of DA neurons in coding reward, but also with the reaction time after a conditioned stimulus, a measure of motivational state. These authors conclude that motivational state affects reward-based learning, and that it is encoded by the dopamine system.
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A section through the ventral thalamus showing antibody labeling for Pax6 (green, nuclear) and R-cadherin (red, cell surface).
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