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A single fear-inducing stimulus induces a transcription-dependent switch in synaptic AMPAR phenotype.

Liu Y, Formisano L, Savtchouk I, Takayasu Y, Szabó G, Zukin RS, Liu SJ - Nat. Neurosci. (2009)

Bottom Line: The subsequent rise in intracellular Ca(2+) and activation of Ca(2+)-sensitive ERK/MAPK signaling triggered new GluR2 gene transcription and a switch in the synaptic AMPAR phenotype from GluR2-lacking, Ca(2+)-permeable receptors to GluR2-containing, Ca(2+)-impermeable receptors on the order of hours.The change in glutamate receptor phenotype altered synaptic efficacy in cerebellar stellate cells.Thus, a single fear-inducing stimulus can induce a long-term change in synaptic receptor phenotype and may alter the activity of an inhibitory neural network.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Pennsylvania State University, University Park, Pennsylvania, USA.

ABSTRACT
Changes in emotional state are known to alter neuronal excitability and can modify learning and memory formation. Such experience-dependent neuronal plasticity can be long-lasting and is thought to involve the regulation of gene transcription. We found that a single fear-inducing stimulus increased GluR2 (also known as Gria2) mRNA abundance and promoted synaptic incorporation of GluR2-containing AMPA receptors (AMPARs) in mouse cerebellar stellate cells. The switch in synaptic AMPAR phenotype was mediated by noradrenaline and action potential prolongation. The subsequent rise in intracellular Ca(2+) and activation of Ca(2+)-sensitive ERK/MAPK signaling triggered new GluR2 gene transcription and a switch in the synaptic AMPAR phenotype from GluR2-lacking, Ca(2+)-permeable receptors to GluR2-containing, Ca(2+)-impermeable receptors on the order of hours. The change in glutamate receptor phenotype altered synaptic efficacy in cerebellar stellate cells. Thus, a single fear-inducing stimulus can induce a long-term change in synaptic receptor phenotype and may alter the activity of an inhibitory neural network.

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Increasing the action potential duration in stellate cells induces a change in rectification of the I–V relationship. A. Duration of spontaneous action potentials in cerebellar stellate cells increased during bath application of TEA at room temperature. B. sEPSCs displayed a nearly linear I–V relationship following TEA treatment (control, n = 5; TEA treatment, n = 6). Cerebellar slices were incubated with kynurenic acid (1 mM) and picrotoxin (100 µM) in the absence (control) or presence of TEA (1 mM, 3 h). C. Summary of rectification index of EPSCs. Cerebellar slices were incubated with 100 µM picrotoxin (n = 5; control, n = 4) or with 1 mM TEA for 3 h (at 37°C, n = 3; at room temperature, n = 6). D. The decay time of sEPSCs increased following TEA treatment (Kolmogorov-Smirnov test, P < 0.0001). Error bars show ± s.e.m.
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Figure 4: Increasing the action potential duration in stellate cells induces a change in rectification of the I–V relationship. A. Duration of spontaneous action potentials in cerebellar stellate cells increased during bath application of TEA at room temperature. B. sEPSCs displayed a nearly linear I–V relationship following TEA treatment (control, n = 5; TEA treatment, n = 6). Cerebellar slices were incubated with kynurenic acid (1 mM) and picrotoxin (100 µM) in the absence (control) or presence of TEA (1 mM, 3 h). C. Summary of rectification index of EPSCs. Cerebellar slices were incubated with 100 µM picrotoxin (n = 5; control, n = 4) or with 1 mM TEA for 3 h (at 37°C, n = 3; at room temperature, n = 6). D. The decay time of sEPSCs increased following TEA treatment (Kolmogorov-Smirnov test, P < 0.0001). Error bars show ± s.e.m.

Mentions: The results thus far indicate that noradrenaline increases action potential firing frequency and prolongs action potential duration in stellate cells. To examine whether either change alone is sufficient to trigger the switch in AMPAR phenotype, we selectively altered action potential frequency or duration. First, we increased spike frequency while maintaining constant spike duration. Block of inhibitory transmission by application of picrotoxin (100 µM) increased action potential firing frequency by 203 ± 72% (n = 5; P < 0.05; Fig. S3), with no change in duration or after-hyperpolarization (Table S2). Picrotoxin (3h) did not alter the rectification index or sEPSC amplitude at stellate cell synapses (Figs. 4C,S3). Hence, an increase in action potential frequency but not duration does not alter synaptic AMPAR phenotype.


A single fear-inducing stimulus induces a transcription-dependent switch in synaptic AMPAR phenotype.

Liu Y, Formisano L, Savtchouk I, Takayasu Y, Szabó G, Zukin RS, Liu SJ - Nat. Neurosci. (2009)

Increasing the action potential duration in stellate cells induces a change in rectification of the I–V relationship. A. Duration of spontaneous action potentials in cerebellar stellate cells increased during bath application of TEA at room temperature. B. sEPSCs displayed a nearly linear I–V relationship following TEA treatment (control, n = 5; TEA treatment, n = 6). Cerebellar slices were incubated with kynurenic acid (1 mM) and picrotoxin (100 µM) in the absence (control) or presence of TEA (1 mM, 3 h). C. Summary of rectification index of EPSCs. Cerebellar slices were incubated with 100 µM picrotoxin (n = 5; control, n = 4) or with 1 mM TEA for 3 h (at 37°C, n = 3; at room temperature, n = 6). D. The decay time of sEPSCs increased following TEA treatment (Kolmogorov-Smirnov test, P < 0.0001). Error bars show ± s.e.m.
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Figure 4: Increasing the action potential duration in stellate cells induces a change in rectification of the I–V relationship. A. Duration of spontaneous action potentials in cerebellar stellate cells increased during bath application of TEA at room temperature. B. sEPSCs displayed a nearly linear I–V relationship following TEA treatment (control, n = 5; TEA treatment, n = 6). Cerebellar slices were incubated with kynurenic acid (1 mM) and picrotoxin (100 µM) in the absence (control) or presence of TEA (1 mM, 3 h). C. Summary of rectification index of EPSCs. Cerebellar slices were incubated with 100 µM picrotoxin (n = 5; control, n = 4) or with 1 mM TEA for 3 h (at 37°C, n = 3; at room temperature, n = 6). D. The decay time of sEPSCs increased following TEA treatment (Kolmogorov-Smirnov test, P < 0.0001). Error bars show ± s.e.m.
Mentions: The results thus far indicate that noradrenaline increases action potential firing frequency and prolongs action potential duration in stellate cells. To examine whether either change alone is sufficient to trigger the switch in AMPAR phenotype, we selectively altered action potential frequency or duration. First, we increased spike frequency while maintaining constant spike duration. Block of inhibitory transmission by application of picrotoxin (100 µM) increased action potential firing frequency by 203 ± 72% (n = 5; P < 0.05; Fig. S3), with no change in duration or after-hyperpolarization (Table S2). Picrotoxin (3h) did not alter the rectification index or sEPSC amplitude at stellate cell synapses (Figs. 4C,S3). Hence, an increase in action potential frequency but not duration does not alter synaptic AMPAR phenotype.

Bottom Line: The subsequent rise in intracellular Ca(2+) and activation of Ca(2+)-sensitive ERK/MAPK signaling triggered new GluR2 gene transcription and a switch in the synaptic AMPAR phenotype from GluR2-lacking, Ca(2+)-permeable receptors to GluR2-containing, Ca(2+)-impermeable receptors on the order of hours.The change in glutamate receptor phenotype altered synaptic efficacy in cerebellar stellate cells.Thus, a single fear-inducing stimulus can induce a long-term change in synaptic receptor phenotype and may alter the activity of an inhibitory neural network.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Pennsylvania State University, University Park, Pennsylvania, USA.

ABSTRACT
Changes in emotional state are known to alter neuronal excitability and can modify learning and memory formation. Such experience-dependent neuronal plasticity can be long-lasting and is thought to involve the regulation of gene transcription. We found that a single fear-inducing stimulus increased GluR2 (also known as Gria2) mRNA abundance and promoted synaptic incorporation of GluR2-containing AMPA receptors (AMPARs) in mouse cerebellar stellate cells. The switch in synaptic AMPAR phenotype was mediated by noradrenaline and action potential prolongation. The subsequent rise in intracellular Ca(2+) and activation of Ca(2+)-sensitive ERK/MAPK signaling triggered new GluR2 gene transcription and a switch in the synaptic AMPAR phenotype from GluR2-lacking, Ca(2+)-permeable receptors to GluR2-containing, Ca(2+)-impermeable receptors on the order of hours. The change in glutamate receptor phenotype altered synaptic efficacy in cerebellar stellate cells. Thus, a single fear-inducing stimulus can induce a long-term change in synaptic receptor phenotype and may alter the activity of an inhibitory neural network.

Show MeSH
Related in: MedlinePlus