Functional differentiation of cholinergic and noradrenergic modulation in a biophysical model of olfactory bulb granule cells

Journal of Neurophysiology
Guoshi LiThomas A Cleland

Abstract

Olfactory bulb granule cells are modulated by both acetylcholine (ACh) and norepinephrine (NE), but the effects of these neuromodulators have not been clearly distinguished. We used detailed biophysical simulations of granule cells, both alone and embedded in a microcircuit with mitral cells, to measure and distinguish the effects of ACh and NE on cellular and microcircuit function. Cholinergic and noradrenergic modulatory effects on granule cells were based on data obtained from slice experiments; specifically, ACh reduced the conductance densities of the potassium M current and the calcium-dependent potassium current, whereas NE nonmonotonically regulated the conductance density of an ohmic potassium current. We report that the effects of ACh and NE on granule cell physiology are distinct and functionally complementary to one another. ACh strongly regulates granule cell firing rates and afterpotentials, whereas NE bidirectionally regulates subthreshold membrane potentials. When combined, NE can regulate the ACh-induced expression of afterdepolarizing potentials and persistent firing. In a microcircuit simulation developed to investigate the effects of granule cell neuromodulation on mitral cell firing properties, ACh increase...Continue Reading

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Citations

Aug 27, 2016·Current Opinion in Neurobiology·Christiane Linster, Thomas A Cleland
Jun 16, 2018·Current Allergy and Asthma Reports·Concepció MarinJoaquim Mullol
Jun 13, 2019·Acta Physiologica·Anan LiDiego Restrepo
Sep 17, 2020·Learning & Memory·Christina Cho, Christiane Linster
Apr 9, 2020·Frontiers in Cellular Neuroscience·Kirill S KorshunovPaul Q Trombley
Feb 23, 2021·The Journal of Comparative Neurology·Sawa HorieKazunori Toida
Dec 24, 2020·Cell and Tissue Research·Daniela Brunert, Markus Rothermel
Apr 10, 2021·Frontiers in Cellular Neuroscience·Timo FischerChristian Lohr

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