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

Abstract

Li G, Linster C, Cleland TA. Functional differentiation of cholinergic and noradrenergic modulation in a biophysical model of olfactory bulb granule cells. J Neurophysiol 114: 3177-3200, 2015. First published September 2, 2015; doi:10.1152/jn.00324.2015.-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 calciumdependent 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 increased spike synchronization among mitral cells, whereas NE modulated the signal-to-noise ratio. Coapplication of ACh and NE both functionally improved the signalto-noise ratio and enhanced spike synchronization among mitral cells. In summary, our computational results support distinct and complementary roles for ACh and NE in modulating olfactory bulb circuitry and suggest that NE may play a role in the regulation of cholinergic function.acetylcholine; norepinephrine; olfactory bulb; computational model; neuromodulation NEUROMODULATORS such as norepinephrine (NE), acetylcholine (ACh), and serotonin serve important functions in sensory perception. These neuromodulatory systems have variously been ascribed specific and often overlapping functions in sensory systems, including improving neuronal signal-to-noise ratios (SNRs), governing attentional processes and general systemic arousal, and regulating learning and memory mechanisms (Aston-Jones and Cohen 2005;Cools et al. 2008;

Spiking and Membrane Properties of Rat Olfactory Bulb Dopamine Neurons

“…Thus, this difference in Na v sensitivity should, at least partially, address the difference in spiking between Large and Small DA neurons (Figure 3Gii). Future studies that could address this difference in spiking could include investigating a potential difference in the density of Na v between Large and Small DA neurons (Zengel et al, 1985;Sengupta et al, 2013), the neuronal localization of these channels (Trimmer and Rhodes, 2004;Kress and Mennerick, 2009), and further analyses of K + currents, including the A-type (Iseppe et al, 2016) and M-currents (Nai et al, 2011;Li et al, 2015). Our reported time constant (13 ms, Figure 4H) is similar to the previously reported 16.8 ms in OB PGCs (Iseppe et al, 2016).…”

“…This means that the constant 10 b also dictates the spiking properties of not only Large and Small neurons, but also those of Top and Bottom neurons (Figures 6C, 7E). Some of the properties that can contribute to the b and m parameters of each neuron include that neuron's action potential threshold (rheobase - Figure 3G), I Na properties, including inactivation (Figures 4E,G), Na v density (Zengel et al, 1985;Sengupta et al, 2013) and distribution throughout the neuron (Trimmer and Rhodes, 2004;Kress and Mennerick, 2009), K + current properties, including the fast-activating and inactivating A-type current (Iseppe et al, 2016) and the non-inactivating M-current (Nai et al, 2011;Li et al, 2015), the I H (Figure 5; Pignatelli et al, 2013), and further biophysical properties. Some of the differences between Top and Bottom neurons may also come from morphological properties, including possessing an axon/AIS (Chand et al, 2015;Galliano et al, 2018) and the growing classification of DA neurons in the OB (Kosaka et al, 2019), among other factors.…”

Precision of Classification of Odorant Value by the Power of Olfactory Bulb Oscillations Is Altered by Optogenetic Silencing of Local Adrenergic Innervation

“…In addition, studies of circuit dynamics in olfactory bulb slices indicate that adrenergic receptor activation leads to long term enhancement of low gamma frequency oscillations in the olfactory bulb (Pandipati et al, 2010 ), however this effect was not observed in animals older than P14 (Pandipati and Schoppa, 2012 ). Finally, computational modeling of the effect of adrenergic modulation on circuit activity and oscillations in the olfactory bulb indicates that adrenergic modulation of oscillatory activity may increase the signal to noise ratio of the circuit (de Almeida et al, 2015 ; Li et al, 2015b ).…”

Complex neural representation of odour information in the olfactory bulb

“…The OB receives significant noradrenergic inputs from the locus coeruleus, which is known to play an important role in arousal, attention and emotional state. Norepinephrine dramatically changes the neural activity in a number of different bulbar cell types, including MCs, GCs and external tufted cells, etc . It activates multiple receptor sub‐types in the OB in a concentration‐dependent manner .…”