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

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. Here we show that a single fear-inducing stimulus increases GluR2 mRNA abundance and promotes synaptic incorporation of GluR2-containing AMPA receptors (AMPARs) in mouse cerebellar stellate cells. The switch in synaptic AMPAR phenotype is mediated by noradrenaline and action potential prolongation. The subsequent rise in intracellular Ca2+ and activation of Ca2+-sensitive ERK /MAPK signaling trigger new GluR2 gene transcription and a switch in the synaptic AMPAR phenotype from GluR2-lacking, Ca2+-permeable, to GluR2-containing Ca2+-impermeable receptors on the order of hours. The change in glutamate receptor phenotype alters 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.

Inhibition of Ca2+-activated large-conductance K+ channel activity alters synaptic AMPA receptor phenotype in mouse cerebellar stellate cells

“…Cerebellar slices (250 m) were obtained from 18-to 22-day-old C57BL/6J mice as described in Liu et al (2010). Slices were maintained in artificial cerebrospinal fluid (ACSF; in mM: 125 NaCl, 2.5 KCl, 2 CaCl 2 , 1 MgCl 2 , 26 NaHCO 3 , 1.25 NaH 2 PO 4 , and 25 glucose, saturated with 95% O 2 -5% CO 2 , pH 7.3) for 60 min before recordings.…”

“…Cerebellar stellate cells fire brief APs (Liu et al 2010). To identify the K ϩ channels that control the AP duration in stellate cells, cells were voltage-clamped at Ϫ100 mV and stepped from Ϫ90 to ϩ60 mV in 10-mV increments.…”

“…To avoid any effect arising from altered presynaptic release, KYNA and PTX were present during all control and BK channel inhibitor treatments. Incubation with KYNA and PTX for 3 h did not alter synaptic currents [rectification index: 0.29 Ϯ 0.03, n ϭ 5; vs. without treatment, 0.34 Ϯ 0.03 (Liu et al 2010); P Ͼ 0.05] and therefore was used as control. KYNA was washed out for 15 min before recording.…”

“…In a recent study, we have shown that noradrenaline increases GluR2 gene transcription and promotes the incorporation of GluR2-containing receptors at synapses in cerebellar stellate cells (Liu et al 2010). This leads to a switch in synaptic AMPAR phenotype from GluR2-lacking, Ca 2ϩ -permeable to GluR2-containing receptors.…”

“…This leads to a switch in synaptic AMPAR phenotype from GluR2-lacking, Ca 2ϩ -permeable to GluR2-containing receptors. Noradrenaline also prolongs the AP duration in cerebellar stellate cells by enhancing an h-current (Liu et al 2010;Saitow and Konishi 2000). Since a subset of K ϩ channels are known to reduce the duration of APs, this raises the possibility that K ϩ currents via these channels may also modulate the expression of postsynaptic AMPARs by controlling AP repolarization.…”