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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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β-adrenergic receptors mediated the olfactory stimulus-induced change in synaptic AMPA receptor subtype. Mice were injected with propranolol or saline (as control) 15–30 min prior to the fox urine exposure. A. A natural olfactory stimulus, fox urine caused fear (measured as a freezing response). % freezing was calculated during the 3 min control and 5 min fox urine exposure period (n = 5; *, P < 0.01). B. Slices were prepared 15 hours after fox urine exposure. Synaptic currents and I–V relationship of EPSCs in stellate cells from the mice pre-injected with saline (n = 6) and propranolol (n = 6). C. Cumulative distribution of EPSC amplitude at +40 mV and decay time constant of EPSC at −60 mV of individual synaptic events from 6 cells under each condition (Kolmogorov-Smirnov test, P < 0.0001, 15 h vs. propranolol). D. Rectification index (***, P < 0.001). Error bars show ± s.e.m.
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Figure 2: β-adrenergic receptors mediated the olfactory stimulus-induced change in synaptic AMPA receptor subtype. Mice were injected with propranolol or saline (as control) 15–30 min prior to the fox urine exposure. A. A natural olfactory stimulus, fox urine caused fear (measured as a freezing response). % freezing was calculated during the 3 min control and 5 min fox urine exposure period (n = 5; *, P < 0.01). B. Slices were prepared 15 hours after fox urine exposure. Synaptic currents and I–V relationship of EPSCs in stellate cells from the mice pre-injected with saline (n = 6) and propranolol (n = 6). C. Cumulative distribution of EPSC amplitude at +40 mV and decay time constant of EPSC at −60 mV of individual synaptic events from 6 cells under each condition (Kolmogorov-Smirnov test, P < 0.0001, 15 h vs. propranolol). D. Rectification index (***, P < 0.001). Error bars show ± s.e.m.

Mentions: Whereas activity-dependent regulation of AMPAR trafficking occurs within 15–30 min after parallel fiber stimulation29,30, the stress-induced switch in synaptic AMPAR phenotype was delayed. Synaptic currents exhibited an inwardly rectifying I–V relation as late as 2 h after fox urine exposure (0.39 ± 0.03, n = 4; Fig 1D,E). Thus, the appearance of GluR2-containing AMPARs at stellate cell synapses does not occur until 2–3 h after a fear-inducing stimulus. The switch in synaptic AMPAR phenotype was long lasting in that synaptic currents exhibited a near linear I–V relationship (0.78 ± 0.08, n = 4; P < 0.01 vs. control, Figs. 1D,E), elevated amplitude at +40 mV (16.6 ±1.7 pA; P < 0.01) and characteristically long decay time at −60 mV (Fig. 2C) as late as 15 h after the fear-inducing stimulus.


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)

β-adrenergic receptors mediated the olfactory stimulus-induced change in synaptic AMPA receptor subtype. Mice were injected with propranolol or saline (as control) 15–30 min prior to the fox urine exposure. A. A natural olfactory stimulus, fox urine caused fear (measured as a freezing response). % freezing was calculated during the 3 min control and 5 min fox urine exposure period (n = 5; *, P < 0.01). B. Slices were prepared 15 hours after fox urine exposure. Synaptic currents and I–V relationship of EPSCs in stellate cells from the mice pre-injected with saline (n = 6) and propranolol (n = 6). C. Cumulative distribution of EPSC amplitude at +40 mV and decay time constant of EPSC at −60 mV of individual synaptic events from 6 cells under each condition (Kolmogorov-Smirnov test, P < 0.0001, 15 h vs. propranolol). D. Rectification index (***, P < 0.001). Error bars show ± s.e.m.
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Related In: Results  -  Collection

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Figure 2: β-adrenergic receptors mediated the olfactory stimulus-induced change in synaptic AMPA receptor subtype. Mice were injected with propranolol or saline (as control) 15–30 min prior to the fox urine exposure. A. A natural olfactory stimulus, fox urine caused fear (measured as a freezing response). % freezing was calculated during the 3 min control and 5 min fox urine exposure period (n = 5; *, P < 0.01). B. Slices were prepared 15 hours after fox urine exposure. Synaptic currents and I–V relationship of EPSCs in stellate cells from the mice pre-injected with saline (n = 6) and propranolol (n = 6). C. Cumulative distribution of EPSC amplitude at +40 mV and decay time constant of EPSC at −60 mV of individual synaptic events from 6 cells under each condition (Kolmogorov-Smirnov test, P < 0.0001, 15 h vs. propranolol). D. Rectification index (***, P < 0.001). Error bars show ± s.e.m.
Mentions: Whereas activity-dependent regulation of AMPAR trafficking occurs within 15–30 min after parallel fiber stimulation29,30, the stress-induced switch in synaptic AMPAR phenotype was delayed. Synaptic currents exhibited an inwardly rectifying I–V relation as late as 2 h after fox urine exposure (0.39 ± 0.03, n = 4; Fig 1D,E). Thus, the appearance of GluR2-containing AMPARs at stellate cell synapses does not occur until 2–3 h after a fear-inducing stimulus. The switch in synaptic AMPAR phenotype was long lasting in that synaptic currents exhibited a near linear I–V relationship (0.78 ± 0.08, n = 4; P < 0.01 vs. control, Figs. 1D,E), elevated amplitude at +40 mV (16.6 ±1.7 pA; P < 0.01) and characteristically long decay time at −60 mV (Fig. 2C) as late as 15 h after the fear-inducing stimulus.

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