Presynaptic actions of kainic acid have been tested on uptake and release mechanisms in synaptosome-enriched preparations from rat hippocampus and goldfish brain. Kainic acid increased in a Ca2+-dependent way the basal release of endogenous glutamate and aspartate from both synaptosomal preparations, with the maximum effect (40-80%) being reached at the highest concentration tested (1 mM). In addition, kainic acid potentiated, in an additive or synergic way, the release of excitatory amino acids stimulated by high K+ concentrations. Kainic acid at 1 mM showed a completely opposite effect on the release of exogenously accumulated D-[3H]aspartate. The drug, in fact, caused a marked inhibition of both the basal and the high K+-stimulated release. Kainic acid at 0.1 mM had no clear-cut effect, whereas at 0.01 mM it caused a small stimulation of the basal release. The present results suggest that kainic acid differentially affects two neurotransmitter pools that are not readily miscible in the synaptic terminals. The release from an endogenous, possibly vesiculate, pool of excitatory amino acids is stimulated, whereas the release from an exogenously accumulated, possibly cytoplasmic and carrier-mediated, pool is inhibited or slightly stimulated, depending on the external concentration of kainic acid. Kainic acid, in addition, strongly inhibits the high-affinity uptake of L-glutamate and D-aspartate in synaptic terminals. All these effects appear specific for excitatory amino acids, making it likely that they are mediated through specific recognition sites present on the membranes of glutamatergic and aspartatergic terminals. The relevance of the present findings to the mechanism of excitotoxicity of kainic acid is discussed.
In neuroscience, Ephs and ephrins are perhaps best known for their role in axon guidance. It was first shown in the visual system that graded expression of these proteins is instrumental in providing molecular coordinates that define topographic maps, particularly in the visual system, but also in the auditory, vomeronasal and somatosensory systems as well as in the hippocampus, cerebellum and other structures. Perhaps unsurprisingly, the role of these proteins in regulating cell-cell interactions also has an impact on cell mobility, with evidence that Eph-ephrin interactions segregate cell populations based on contact-mediated attraction or repulsion. Consistent with these studies, evidence has accumulated that Ephs and ephrins play important roles in the migration of specific cell populations in the developing and adult brain. This review focusses on two examples of neuronal migration that require Eph/ephrin signalling – radial and tangential migration of neurons in cortical development and the migration of newly generated neurons along the rostral migratory stream to the olfactory bulb in the adult brain. We discuss the challenge involved in understanding how cells determine whether they respond to signals by migration or axon guidance.
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