Intrinsic plasticity induced by group II metabotropic glutamate receptors via enhancement of high-threshold KV currents in sound localizing neurons

Abstract

Intrinsic plasticity has emerged as an important mechanism regulating neuronal excitability and output under physiological and pathological conditions. Here, we report a novel form of intrinsic plasticity. Using perforated patch clamp recordings, we examined the modulatory effects of group II metabotropic glutamate receptors (mGluR II) on voltage-gated potassium (KV) currents and the firing properties of neurons in the chicken nucleus laminaris (NL), the first central auditory station where interaural time cues are analyzed for sound localization. We found that activation of mGluR II by synthetic agonists resulted in a selective increase of the high threshold KV currents. More importantly, synaptically released glutamate (with reuptake blocked) also enhanced the high threshold KV currents. The enhancement was frequency-coding region dependent, being more pronounced in low frequency neurons compared to middle and high frequency neurons. The intracellular mechanism involved the Gβγ signaling pathway associated with phospholipase C and protein kinase C. The modulation strengthened membrane outward rectification, sharpened action potentials, and improved the ability of NL neurons to follow high frequency inputs. These data suggest that mGluR II provides a feedforward modulatory mechanism that may regulate temporal processing under the condition of heightened synaptic inputs.

Cross-compartmental Modulation of Dendritic Signals for Retinal Direction Selectivity

“…A strong molecular candidate is metabotropic glutamate receptor 2 (mGluR2), which is primarily expressed in SACs postsynaptically to bipolar cell synapses, but not in bipolar or ganglion cells (Cai and Pourcho, 1999; Koulen et al, 1996; Seebahn et al, 2008). mGluR2 activation is known to promote neuronal excitability by modulating voltage-gated conductances (Bischofberger and Schild, 1996; Hamlet and Lu, 2016; Ikeda et al, 1995; Knoflach and Kemp, 1998; Kupferschmidt and Lovinger, 2015; Saugstad et al, 1996; Taniguchi et al, 2013) and to influence spiking responses of DSGCs (Jensen, 2006). Nevertheless, the role of mGluR2 in SAC dendritic computation is unknown.…”

Anatomy and Physiology of Metabotropic Glutamate Receptors in Mammalian and Avian Auditory System

“…Supporting this notion, we recently observed that activation of mGluRs enhanced high voltage-gated K + channel currents in timing coding neurons in the auditory brainstem. Critically, the modulation was only detected under perforated patch recording but not under conventional whole-cell recording [54].…”

Neuromodulation by mGluRs in Sound Localization Circuits in the Auditory Brainstem

“…Therefore, the anti-homeostatic plasticity observed after hearing deprivation is unlikely a reversion to the pre-hearing status. Besides, the intrinsic neuronal properties of NL neurons are also regulated by mGluRs in a coding frequency-dependent manner (Hamlet and Lu, 2016 ). By using a technique that preserves intracellular signaling pathways (perforated patch-clamp recording), we reported that the high threshold K V currents in NL neurons are enhanced, with the strongest modulation in LF neurons.…”

“…By using a technique that preserves intracellular signaling pathways (perforated patch-clamp recording), we reported that the high threshold K V currents in NL neurons are enhanced, with the strongest modulation in LF neurons. This mGluR enhancement of K V currents renders NL neurons the ability to follow high-frequency inputs, via an increase in the membrane outward rectification and sharpening of the waveform of APs (Hamlet and Lu, 2016 ). We propose that this modulation provides a feedforward modulatory mechanism that enhances temporal processing, especially when the peripheral input is of high intensity.…”