Progress in neurobiology
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Progress in neurobiology · Apr 1998
ReviewPharmacology of glutamate receptor antagonists in the kindling model of epilepsy.
It is widely accepted that excitatory amino acid transmitters such as glutamate are involved in the initiation of seizures and their propagation. Most attention has been directed to synapses using NMDA receptors, but more recent evidence indicates potential roles for ionotropic non-NMDA (AMPA/kainate) and metabotropic glutamate receptors as well. Based on the role of glutamate in the development and expression of seizures, antagonism of glutamate receptors has long been thought to provide a rational strategy in the search for new, effective anticonvulsant drugs. ⋯ In contrast, ionotropic non-NMDA receptor antagonists exert potent anticonvulsant effects on both initiation and propagation of kindled seizures. This effect can be markedly potentiated by combination with low doses of NMDA antagonists, suggesting that an optimal treatment of focal and secondarily generalized seizures may require combined use of both non-NMDA and NMDA antagonists. Given the promising results obtained with novel AMPA/kainate antagonists and glycine/NMDA partial agonists in the kindling model, the hope for soon having potentially useful glutamate antagonists for use in epileptic patients is increasing.
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Progress in neurobiology · Jul 1997
ReviewMetaplasticity: a new vista across the field of synaptic plasticity.
Over the past 20 years there has been an increasing understanding of the properties and mechanisms underlying long-term potentiation (LTP) and long-term depression (LTD) of synaptic efficacy, putative learning and memory mechanisms in the mammalian brain. More recently, however, it has become apparent that synaptic activity can also elicit persistent neuronal responses not manifest as changes in synaptic strength. Some of these changes may nonetheless modify the ability of synapses to undergo strength changes in response to subsequent episodes of synaptic activity. ⋯ The mechanisms underlying such phenomena remain to be fully characterized, although some likely possibilities are an altered N-methyl-D-aspartate receptor function, altered calcium buffering, altered states of kinases or phosphatases, and a priming of protein synthesis machinery. While some details vary, experimentally observed metaplasticity bears some similarity to the "sliding threshold" feature of the Bienenstock, Cooper and Munro model of experience-dependent synaptic plasticity. Metaplasticity may serve several functions including (1) providing a way for synapses to integrate a response across temporally spaced episodes of synaptic activity and (2) keeping synapses within a dynamic functional range, and thus preventing them from entering states of saturated LTP or LTD.
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Progress in neurobiology · Jun 1997
ReviewThe neurobiology of placebo analgesia: from endogenous opioids to cholecystokinin.
Placebo is a widespread phenomenon in medicine and biology and its mechanisms are understood only partially. Most of our understanding of placebo comes from studies on pain. In particular, placebo analgesia represents a situation where the administration of a substance known to be non-analgesic produces an analgesic response when the subject is told that it is a pain killer. ⋯ This claim comes from the observation that the opioid antagonist naloxone can reverse placebo analgesia. On the basis of the discovery of the anti-opioid action of the neuropeptide cholecystokinin, recent studies demonstrate that the blockade of cholecystokinin receptors potentiates the placebo analgesic response, thus suggesting an inhibitory role of cholecystokinin in placebo analgesia. Thus, by antagonizing the anti-opioid action of cholecystokinin during a placebo procedure, a potentiation of the endogenous opioid systems can be obtained.
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Progress in neurobiology · Sep 1996
ReviewThe organization and function of endogenous antinociceptive systems.
Much progress has been made the understanding of endogenous pain-controlling systems. Recently, new concepts and ideas which are derived from neurobiology, chaos research and from research on learning and memory have been introduced into pain research and shed further light on the organization and function of endogenous antinociception. ⋯ Results demonstrate that characteristic activity patterns result within and outside the PAG when stimulating at its various subdivisions. The descending systems may not only depress mean discharge rates of nociceptive spinal dorsal horn neurons, but also may modify harmonic oscillations and nonlinear dynamics (dimensionality) of discharges. (2) Propriospinal, heterosegmental inhibition: antinociceptive, heterosegmental interneurons exist which may be activated by noxious stimulation or by supraspinal descending pathways. (3) Segmental spinal inhibition: a robust long-term depression of primary afferent neurotransmission in A delta fibers has been identified in superficial spinal dorsal horn which may underlie long-lasting antinociception by afferent stimulation, e.g. by physical therapy or acupuncture.
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It is established that astrocytes are the intimate partner of neurons throughout their lifespan. However, astrocytes play different roles at different stages of the lifespan. During neurogenesis and early development, glial cells provide a scaffold for the correct migration of neurons and growth cones. ⋯ Thus, astrocytes can be expected to modify the expression of endogenous neurotoxins and thus contribute to synaptic plasticity in ageing. Synaptic plasticity continues to be a homeostatic relationship between neurons and glial cells. The possibility of signaling from astrocytes to neurons has opened new horizons for glial cell function and new challenges of research for gliobiologists.