Biomedical subjects

David L Glanzman

Publications and source records attributed to David L Glanzman.

5 recordsLinked to original sources

PubMed2006

The cellular mechanisms of learning in Aplysia: of blind men and elephants.

Until recently, investigations of the neurobiological substrates of simple forms of learning and memory in the marine snail Aplysia have focused mostly on plastic changes that occur within the presynaptic sensory neurons. Here, I summarize the results of recent studies that indicate that exclusively presynaptic processes cannot account for simple forms of learning in Aplysia. In particular, I present evidence that postsynaptic mechanisms play a far more important role in nonassociative learning in Aplysia than has been appreciated before now. Moreover, I describe recent data that suggests the intriguing hypothesis that the persistent, learning-induced changes in Aplysia sensory neurons might depend critically on postsynaptic signals for their induction. Finally, I discuss the potential applicability of this hypothesis to learning-related synaptic plasticity in the mammalian brain.

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PubMed2005

Synaptic facilitation and behavioral dishabituation in Aplysia: dependence on release of Ca2+ from postsynaptic intracellular stores, postsynaptic exocytosis, and modulation of postsynaptic AMPA receptor efficacy.

Sensitization and dishabituation of the defensive withdrawal reflex in Aplysia have been ascribed to presynaptic mechanisms, particularly presynaptic facilitation of transmission at sensorimotor synapses in the CNS of Aplysia. Here, we show that facilitation of sensorimotor synapses in cell culture during and after serotonin (5-HT) exposure depends on a rise in postsynaptic intracellular Ca(2+) and release of Ca(2+) from postsynaptic stores. We also provide support for the idea that postsynaptic AMPA receptor insertion mediates a component of synaptic facilitation by showing that facilitation after 5-HT offset is blocked by injecting botulinum toxin, an exocytotic inhibitor, into motor neurons before application of 5-HT. Using a reduced preparation, we extend our results to synaptic facilitation in the abdominal ganglion. We show that tail nerve shock-induced facilitation of siphon sensorimotor synapses also depends on elevated postsynaptic Ca(2+) and release of Ca(2+) from postsynaptic stores and recruits a late phase of facilitation that involves selective enhancement of the AMPA receptor-mediated synaptic response. To examine the potential role of postsynaptic exocytosis of AMPA receptors in learning in Aplysia, we test the effect of injecting botulinum toxin into siphon motor neurons on dishabituation of the siphon-withdrawal reflex. We find that postsynaptic injections of the toxin block dishabituation resulting from tail shock. Our results indicate that postsynaptic mechanisms, particularly Ca(2+)-dependent modulation of AMPA receptor trafficking, play a critical role in synaptic facilitation as well as in dishabituation and sensitization in Aplysia.

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PubMed2005

Associative learning: Hebbian flies.

Fruit flies can learn to associate an odor with an aversive stimulus, such as a shock. New findings indicate that disrupting the expression of N-methyl-D-aspartate (NMDA) receptors in flies impairs olfactory conditioning. The findings provide support for a critical role for NMDA receptors in associative learning.

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PubMed2003

Prolonged habituation of the gill-withdrawal reflex in Aplysia depends on protein synthesis, protein phosphatase activity, and postsynaptic glutamate receptors.

Despite representing perhaps the simplest form of memory, habituation is not yet well understood mechanistically. We used a reduced preparation to analyze the neurobiological mechanisms of persistent habituation of a simple behavior, the defensive withdrawal reflex of the marine snail Aplysia californica. This preparation permits direct infusion of drugs into the abdominal ganglion during training via a cannula in the abdominal artery. Using siphon-elicited gill withdrawal, we demonstrate habituation of withdrawal that persists for 1-6 hr after repeated, spaced blocks of habituating stimulation. This form of habituation exhibits site specificity and requires protein synthesis because it is blocked by the presence of anisomycin, a protein synthesis inhibitor. We also find that habituation of gill withdrawal requires protein phosphatase activity, because it is blocked by okadaic acid, an inhibitor of protein phosphatase. Finally, habituation of gill withdrawal requires activation of NMDA-type and AMPA-type postsynaptic receptors within the abdominal ganglion, because it is blocked by infusion of dl-2-amino-5-phosphonovaleric acid or 6,7-dinitroquinoxaline-2,3-dione. The requirement for activation of postsynaptic glutamatergic receptors indicates that homosynaptic depression, an exclusively presynaptic mechanism that has been implicated previously in habituation in Aplysia, does not play a significant role in persistent habituation of the withdrawal reflex. Our results indicate that postsynaptic mechanisms, possibly including modulation of glutamate receptor function, play a major, heretofore unsuspected, role in habituation in Aplysia.

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PubMed2003

Learning in Aplysia: looking at synaptic plasticity from both sides.

Until recently, learning and memory in invertebrate organisms was believed to be mediated by relatively simple presynaptic mechanisms. By contrast, learning and memory in vertebrate organisms is generally thought to be mediated, at least in part, by postsynaptic mechanisms. But new experimental evidence from research using a model invertebrate organism, the marine snail Aplysia, indicates that this apparent distinction between invertebrate and vertebrate synaptic mechanisms of learning is invalid: learning in Aplysia cannot be explained in terms of exclusively presynaptic mechanisms. NMDA-receptor-dependent LTP appears to be necessary for classical conditioning in Aplysia. Furthermore, modulation of trafficking of postsynaptic ionotropic glutamate receptors underlies behavioral sensitization in this snail. Exclusively presynaptic processes appear to support only relatively brief memory in Aplysia. More persistent memory is likely to be mediated by postsynaptic processes, or by presynaptic processes whose expression depends upon retrograde signals.

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