The role of kinases and phosphatases in the signal transduction of hippocampal pyramidal cells.
Item
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Title
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The role of kinases and phosphatases in the signal transduction of hippocampal pyramidal cells.
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Identifier
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AAI9605643
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identifier
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9605643
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Creator
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Nouranifar, Rabin.
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Contributor
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Adviser: Emmanuel Landau
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Date
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1995
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Neuroscience | Biology, Animal Physiology
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Abstract
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The role of the cAMP pathway in long-term potentiation (LTP) was studied in the CA1 region of hippocampus. Widely-spaced trains of high-frequency stimulation (HFS) generated cAMP postsynaptically via NMDA receptors and calmodulin, consistent with the Ca{dollar}\sp{lcub}2+{rcub}{dollar}/calmodulin-mediated stimulation of postsynaptic adenylyl cyclase. The early phase of LTP produced by the same pattern of HFS was dependent on postsynaptic cAMP. However, synaptic transmission was not increased by postsynaptic application of cAMP. Early LTP became cAMP-independent when protein phosphatase inhibitors were injected postsynaptically. These observations indicate that in early LTP the cAMP signaling pathway, instead of transmitting signals for the generation of LTP, gates LTP through postsynaptic protein phosphatases.;Intracellular and whole-cell recording techniques were used to investigate the interaction between the metabotropic glutamate and {dollar}\beta{dollar}-adrenergic signaling pathways in pyramidal cells from the CA1 region of adult rat hippocampal slices. cis-aminocyclopentane-1,3-dicarboxylate (known as trans-ACPD), Norepinephrine (NE) and isoproterenol(ISO) blocked the slow afterhyperpolarization (sAHP) evoked by membrane depolarization when applied individually. However, the effects of the combined NE/ACPD or ISO/ACPD application did not exceed that of either drug alone. A larger effect of the combined agonists was obtained when protein kinase C (PKC) was inhibited. The ISO-ACPD interaction could be mimicked by the combination of 8-bromo-cAMP and phorbol dibutyrate. The results indicate that the metabotropic glutamate pathway coupled to PKC limits the b-adrenergic inhibition of the sAHP. The demonstration that PKC can prevent an effect of the cAMP pathway reveals a potentially important motif of interaction between these two pathways, expressed as an assignment of ranks to different neurotransmitters acting on a common effector. Thus, a neurotransmitter of a higher rank (glutamate, coupled to PKC) can override the effect of a lower-ranking transmitter (norepinephrine, coupled to cAMP), enabling the neuron to discriminate among neurotransmitters released in temporal proximity.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
