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Individual GABAergic interneurons in hippocampus can powerfully inhibit more than a thousand excitatory pyramidal neurons. Therefore, control of interneuron excitability provides control over hippocampal networks. We have identified a novel mechanism in hippocampus that weakens excitatory synapses onto GABAergic interneurons. Following stimulation that elicits long-term potentiation at neighboring...
High levels of familial Amyotrophic Lateral Sclerosis (ALS)-linked SOD1 mutants G93A and G37R were previously shown to mediate disease in mice through an acquired toxic property. We report here that even low levels of another mutant, G85R, cause motor neuron disease characterized by an extremely rapid clinical progression, without changes in SOD1 activity. Initial indicators of disease are astrocytic...
We asked whether GABAA and NMDA receptors may act in synergy in neonatal hippocampal slices, at a time when GABA exerts a depolarizing action. The GABAA receptor agonist isoguvacine reduced the voltage-dependent Mg2+ block of single NMDA channels recorded in cell-attached configuration from P2–5 CA3 pyramidal neurons and potentiated the Ca2+ influx through NMDA channels. The synaptic response evoked...
The performance of a task is often assumed to be a prerequisite for the learning of many tasks, including the associative conditioning of courtship in the fruit fly, Drosophila melanogaster. Transgenic flies specifically inhibited for the enzyme protein kinase C dissociate the acquisition of learning and memory from performance of the task. They fail to show immediate suppression of courtship but...
We show that the proliferation of astrocytes in the developing rodent optic nerve absolutely depends on axons and that this axonal influence depends on axonal transport but not on axonal electrical activity. We also show that purified retinal ganglion cells stimulate DNA synthesis in optic nerve astrocytes in culture and that the effect can be mimicked by fibroblast growth factor but not by neuregulins...
During development, activity-dependent mechanisms are thought to contribute to the refinement of topographical projections from the thalamus to the cortex. Because activity-dependent increases in synaptic strength may contribute to the stabilization of synaptic connections, we have explored the mechanisms of long-term potentiation (LTP) at thalamocortical synapses in rat somatosensory (barrel) cortex...
During development, growing motor axons are excluded from the ventral midline of the neural tube by diffusible chemorepellents emanating from this region. Molecular candidates for this chemorepellent activity include semaphorin D and netrin-1; the latter is known to repel trochlear motor axons. Qualitatively or quantitatively different responses to these molecules might underlie the initial deflection...
In this report, we have examined the role of neuron-derived BDNF at an accessible synapse, that of preganglionic neurons onto their sympathetic neuron targets. Developing and mature sympathetic neurons synthesize BDNF, and preganglionic neurons express the full-length BDNF/TrkB receptor. When sympathetic neuron-derived BDNF is increased 2- to 4-fold in transgenic mice, preganglionic cell bodies and...
The cell adhesion molecules (CAMs) NCAM, N-cadherin, and L1 are homophilic binding molecules that stimulate axonal growth. We have postulated that the above CAMs can stimulate this response by activating the fibroblast growth factor receptor (FGFR) in neurons. In the present study, we demonstrate that activation of NCAM and L1 can lead to phosphorylation of the FGFR. Both this and the neurite outgrowth...
Mechanisms underlying the learned vocal behavior of songbirds were studied by examining expression of the protein product of the immediate early gene c-fos (Fos) in zebra finches. Auditory stimuli including the bird's own song did not induce Fos in the song system. In contrast, the motor act of singing induced Fos in two song sensorimotor nuclei, HVc and RA. This induction was independent of auditory...
Axonin-1 and NrCAM were previously shown to be involved in the in vivo guidance of commissural growth cones across the floor plate of the embryonic chicken spinal cord. To further characterize their role in axon pathfinding, we developed a two-dimensional coculture system of commissural and floor-plate explants in which it was possible to study the behavior of growth cones upon floor- plate contact...
At excitatory synapses on CA1 pyramidal cells of the hippocampus, a larger quantal content is sensed by N-methyl-D-aspartic acid receptors (NMDARs) than by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). A novel explanation for this discrepancy is that glutamate released from terminals presynaptic to one cell can diffuse to and activate NMDARs, but not AMPARs, on a neighboring...
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