Mechanisms of Noradrenergic Modulation of Dentate Gyrus Long-Term Plasticity
Since D. O. Hebb (1949) inaugurated the search for cellular mechanisms underlying brain function and behavioral plasticity, many strategies and model systems have been employed. One fruitful strategy has been the search for specific chemical transmitters able to modulate firing patterns of neurons in specific pathways for long periods of time. A promising model system has arisen from the discovery that brief, high-frequency stimulation of afferent pathways in the hippocampus leads to long-lasting enhancements of neuronal excitability whose persistence approach that of conditioned behavior (Bliss and Gardner-Medwin, 1973; Douglas and Goddard, 1975). The enhancement of evoked potentials after one such tetanus has been termed long-term potentiation (LTP; Bliss and Lømo, 1973; Schwartzkroin and Wester, 1975; Alger and Teyler, 1976), and repeated application of such stimulation yields the seizure state known as kindled epilepsy (Goddard et al., 1969). In both cases, the location of such long-lasting plasticity in a brain structure implicated in memory processes (Milner, 1972; Berger, 1984), its production by brief (a few seconds) stimulation within the physiological range (10–400 Hz), and the long duration of the changes (months in vivo) all led to extreme interest in their underlying mechanisms (Swanson et al., 1982).
KeywordsNMDA Receptor Granule Cell Dentate Gyrus Hippocampal Slice Granule Cell Layer
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