Freely moving rats received high-frequency stimulation of the perforant path-granule cell pathway... more Freely moving rats received high-frequency stimulation of the perforant path-granule cell pathway during slow-wave sleep (SWS) and during a still-alert (SAL) behavioral state. Trains given in SAL induced LTP of the dentate population spike height, spike onset latency, and the epsp-spike relation more often than did trains delivered in SWS. In some cases tetanization in SWS was followed by a long-term depression (LTD) of these field potential measures. The results suggest that the ability of hippocampal neurons to undergo long-term synaptic plasticity is dynamically modified according to the behavioral state of the animal.
SUMMARYThe mRNA cap-binding protein, eukaryotic initiation factor 4E (eIF4E), is crucial for tran... more SUMMARYThe mRNA cap-binding protein, eukaryotic initiation factor 4E (eIF4E), is crucial for translation and regulated by Ser209 phosphorylation. However, the biochemical and physiological role of eIF4E phosphorylation in translational control of long-term synaptic plasticity is unknown. We demonstrate that phospho-ablated Eif4eS209A knockin mice are profoundly impaired in dentate gyrus LTP maintenance in vivo, while basal perforant path-evoked transmission and LTP induction are intact. mRNA cap-pulldown assays show that phosphorylation is required for synaptic activity-induced removal of translational repressors from eIF4E, allowing initiation complex formation. Using ribosome profiling, we identified selective, phospho-eIF4E-dependent translation of the Wnt signaling pathway in in vivo LTP. Surprisingly, the canonical Wnt effector, β-catenin, was massively recruited to the eIF4E cap complex following LTP induction in wild-type, but not Eif4eS209A, mice. These results demonstrate a...
Major learning events are typically followed by a period during which the number and/or duration ... more Major learning events are typically followed by a period during which the number and/or duration of rapid-eye movement sleep episodes is increased. Processes critical to memory formation are thought to take place during this interval of 'enhanced' rapid-eye movement sleep. We therefore compared the capacity for long-term potentiation during rapid-eye movement sleep and alert wakefulness after learning. Rats were chronically implanted with electrodes for stimulation of the perforant path and recording of evoked potentials and EEG in the dentate gyrus. After obtaining baseline recordings, rats were trained on a 40-trial two-way active avoidance task. Conditioned rats exhibited a two-fold increase in the mean duration of rapid-eye movement sleep episodes, as reflected by a prolongation of the hippocampal theta rhythm. There was no change in the sleep pattern of pseudoconditioned controls, which received explicitly unpaired tones and foot shocks in a yoked design. High-frequency stimulation was applied during the second, third, and fourth major rapid-eye movement sleep episodes after active avoidance training. Another group was tetanized at matching time points during alert wakefulness. After pseudoconditioning, tetanus applied during wakefulness or rapid-eye movement sleep readily induced long-term potentiation, and there was no difference between groups in the magnitude of increase for the population excitatory postsynaptic potential slope or the population spike height as measured 1 h, 24 h, and 5 days post-tetanus.(ABSTRACT TRUNCATED AT 250 WORDS)
Page 1. EVAPORATIVE WATER LOSS AND OXYGEN CONSUMPTION OF THREE SMALL LIZARDS FROM THE FLORIDA KEY... more Page 1. EVAPORATIVE WATER LOSS AND OXYGEN CONSUMPTION OF THREE SMALL LIZARDS FROM THE FLORIDA KEYS: SPHAERODACTYLUS CINEREUS, S. NOTATUS, AND ANOLIS SAGREI1 WILLIAM A. DUNSON ...
In model membranes, arachidonic acid and diacylglycerol have been proposed to synergistically ind... more In model membranes, arachidonic acid and diacylglycerol have been proposed to synergistically induce a membrane-inserted, constitutively active form of protein kinase C. We have investigated the effects of these lipid protein kinase C activators on synaptic efficacy in the Schaffer collateral input to CA1 hippocampal pyramidal cells. Arachidonic acid (5 microM) perfusion combined with repetitive afferent stimulation had no consistent effect on field excitatory postsynaptic potentials recorded in stratum radiatum, while treatment with a cell-permeable diglyceride, oleoyl-acetylglycerol (5 micrograms/ml), followed by stimulation, led to a short-term potentiation. By contrast, the combination of oleoyl-acetylglycerol and arachidonic acid gave rise to a long-lasting non-decremental potentiation of field excitatory postsynaptic potentials. The induction of potentiation was "activity dependent", as there was either no significant effect or there was a measurable depression when repetitive synaptic stimulation was omitted. Furthermore, consistent with a protein kinase C-dependent process, the potentiation was blocked by the kinase inhibitors H-7 and staurosporine. The results suggest that relatively low concentrations of arachidonic acid and diacylglycerol work synergistically through protein kinase C to persistently enhance synaptic transmission. This synergy has the makings of an associative (Hebbian) device for long-term potentiation induction operating at the second messenger level.
Freely moving rats received high-frequency stimulation of the perforant path-granule cell pathway... more Freely moving rats received high-frequency stimulation of the perforant path-granule cell pathway during slow-wave sleep (SWS) and during a still-alert (SAL) behavioral state. Trains given in SAL induced LTP of the dentate population spike height, spike onset latency, and the epsp-spike relation more often than did trains delivered in SWS. In some cases tetanization in SWS was followed by a long-term depression (LTD) of these field potential measures. The results suggest that the ability of hippocampal neurons to undergo long-term synaptic plasticity is dynamically modified according to the behavioral state of the animal.
SUMMARYThe mRNA cap-binding protein, eukaryotic initiation factor 4E (eIF4E), is crucial for tran... more SUMMARYThe mRNA cap-binding protein, eukaryotic initiation factor 4E (eIF4E), is crucial for translation and regulated by Ser209 phosphorylation. However, the biochemical and physiological role of eIF4E phosphorylation in translational control of long-term synaptic plasticity is unknown. We demonstrate that phospho-ablated Eif4eS209A knockin mice are profoundly impaired in dentate gyrus LTP maintenance in vivo, while basal perforant path-evoked transmission and LTP induction are intact. mRNA cap-pulldown assays show that phosphorylation is required for synaptic activity-induced removal of translational repressors from eIF4E, allowing initiation complex formation. Using ribosome profiling, we identified selective, phospho-eIF4E-dependent translation of the Wnt signaling pathway in in vivo LTP. Surprisingly, the canonical Wnt effector, β-catenin, was massively recruited to the eIF4E cap complex following LTP induction in wild-type, but not Eif4eS209A, mice. These results demonstrate a...
Major learning events are typically followed by a period during which the number and/or duration ... more Major learning events are typically followed by a period during which the number and/or duration of rapid-eye movement sleep episodes is increased. Processes critical to memory formation are thought to take place during this interval of 'enhanced' rapid-eye movement sleep. We therefore compared the capacity for long-term potentiation during rapid-eye movement sleep and alert wakefulness after learning. Rats were chronically implanted with electrodes for stimulation of the perforant path and recording of evoked potentials and EEG in the dentate gyrus. After obtaining baseline recordings, rats were trained on a 40-trial two-way active avoidance task. Conditioned rats exhibited a two-fold increase in the mean duration of rapid-eye movement sleep episodes, as reflected by a prolongation of the hippocampal theta rhythm. There was no change in the sleep pattern of pseudoconditioned controls, which received explicitly unpaired tones and foot shocks in a yoked design. High-frequency stimulation was applied during the second, third, and fourth major rapid-eye movement sleep episodes after active avoidance training. Another group was tetanized at matching time points during alert wakefulness. After pseudoconditioning, tetanus applied during wakefulness or rapid-eye movement sleep readily induced long-term potentiation, and there was no difference between groups in the magnitude of increase for the population excitatory postsynaptic potential slope or the population spike height as measured 1 h, 24 h, and 5 days post-tetanus.(ABSTRACT TRUNCATED AT 250 WORDS)
Page 1. EVAPORATIVE WATER LOSS AND OXYGEN CONSUMPTION OF THREE SMALL LIZARDS FROM THE FLORIDA KEY... more Page 1. EVAPORATIVE WATER LOSS AND OXYGEN CONSUMPTION OF THREE SMALL LIZARDS FROM THE FLORIDA KEYS: SPHAERODACTYLUS CINEREUS, S. NOTATUS, AND ANOLIS SAGREI1 WILLIAM A. DUNSON ...
In model membranes, arachidonic acid and diacylglycerol have been proposed to synergistically ind... more In model membranes, arachidonic acid and diacylglycerol have been proposed to synergistically induce a membrane-inserted, constitutively active form of protein kinase C. We have investigated the effects of these lipid protein kinase C activators on synaptic efficacy in the Schaffer collateral input to CA1 hippocampal pyramidal cells. Arachidonic acid (5 microM) perfusion combined with repetitive afferent stimulation had no consistent effect on field excitatory postsynaptic potentials recorded in stratum radiatum, while treatment with a cell-permeable diglyceride, oleoyl-acetylglycerol (5 micrograms/ml), followed by stimulation, led to a short-term potentiation. By contrast, the combination of oleoyl-acetylglycerol and arachidonic acid gave rise to a long-lasting non-decremental potentiation of field excitatory postsynaptic potentials. The induction of potentiation was "activity dependent", as there was either no significant effect or there was a measurable depression when repetitive synaptic stimulation was omitted. Furthermore, consistent with a protein kinase C-dependent process, the potentiation was blocked by the kinase inhibitors H-7 and staurosporine. The results suggest that relatively low concentrations of arachidonic acid and diacylglycerol work synergistically through protein kinase C to persistently enhance synaptic transmission. This synergy has the makings of an associative (Hebbian) device for long-term potentiation induction operating at the second messenger level.
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