Activation of InsP(3) receptors is sufficient for inducing graded intrinsic plasticity in rat hippocampal pyramidal neurons

Ashhad, Sufyan and Johnston, Daniel and Narayanan, Rishikesh (2015) Activation of InsP(3) receptors is sufficient for inducing graded intrinsic plasticity in rat hippocampal pyramidal neurons. In: JOURNAL OF NEUROPHYSIOLOGY, 113 (7). pp. 2002-2013.

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Abstract

The synaptic plasticity literature has focused on establishing necessity and sufficiency as two essential and distinct features in causally relating a signaling molecule to plasticity induction, an approach that has been surprisingly lacking in the intrinsic plasticity literature. In this study, we complemented the recently established necessity of inositol trisphosphate (InsP(3)) receptors (InsP(3)R) in a form of intrinsic plasticity by asking if InsP(3)R activation was sufficient to induce intrinsic plasticity in hippocampal neurons. Specifically, incorporation of D-myo-InsP(3) in the recording pipette reduced input resistance, maximal impedance amplitude, and temporal summation but increased resonance frequency, resonance strength, sag ratio, and impedance phase lead. Strikingly, the magnitude of plasticity in all these measurements was dependent on InsP 3 concentration, emphasizing the graded dependence of such plasticity on InsP(3)R activation. Mechanistically, we found that this InsP(3)-induced plasticity depended on hyperpolarization-activated cyclic nucleotide-gated channels. Moreover, this calcium-dependent form of plasticity was critically reliant on the release of calcium through InsP(3)Rs, the influx of calcium through N-methyl-D-aspartate receptors and voltage-gated calcium channels, and on the protein kinase A pathway. Our results delineate a causal role for InsP(3)Rs in graded adaptation of neuronal response dynamics, revealing novel regulatory roles for the endoplasmic reticulum in neural coding and homeostasis.

Item Type:	Journal Article
Publication:	JOURNAL OF NEUROPHYSIOLOGY
Publisher:	AMER PHYSIOLOGICAL SOC
Additional Information:	Copy right for this article belongs to the AMER PHYSIOLOGICAL SOC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
Keywords:	endoplasmic reticulum; HCN channels; hippocampus; inositol trisphosphate receptors; intrinsic plasticity
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	26 Jun 2015 08:00
Last Modified:	26 Jun 2015 08:00
URI:	http://eprints.iisc.ac.in/id/eprint/51784

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