Cholinergic Modulation of Neuronal Excitability in the Accessory Olfactory Bulb

Abstract

The accessory olfactory bulb (AOB), the first relay of chemosensory information in the Vomeronasal system, receives extensive cholinergic innervation from the basal forebrain. Cholinergic modulation of neuronal activity in the olfactory bulb has been hypothesized to play an important role in olfactory processing; however, little is known about the cellular actions of acetylcholine (ACh) within the AOB. Here using in vitro slice preparation, we show that muscarinic acetylcholine receptor (mAChR) activation increases neuronal excitability of granule and mitral/tufted cells (GCs and MCs) in the AOB. Activation of mAChRs increased excitability of GCs by three distinct mechanisms: induction of a long-lasting depolarization, activation of a slow afterdepolarization (sADP), and an increase in excitatory glutamatergic input due to MC depolarization. The depolarization and sADP were elicited by the selective agonist 4-[[[(3-chlorophenyl)amino]carbonyl]oxy]-N,N,N-trimethyl-2-butyn-1-aminium chloride (100 μM) and blocked by low concentrations of pirenzepine (300 nM), indicating that they result from activation of M1-like mAChRs. In contrast, cholinergic stimulation increased the excitability of MCs via recruitment of nicotinic AChRs (nAChRs) and M1-like mAChRs. Submaximal activation of these receptors, however, decreased the excitability of MCs. Surprisingly, we found that unlike GCs in the main olfactory bulb, GCs in the AOB are excited by mAChR activation in young postnatal neurons, suggesting marked differences in cholinergic regulation of development between these two regions of the olfactory bulb.

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

“…ACh enhances GC excitability by inhibiting two potassium currents, I M and I AHP , which underlie frequency adaptation and are responsible for generating medium and slow AHP responses (respectively) in GCs. Blockage of these two currents uncovers a Ca 2ϩ -activated nonspecific cation current I CAN that transforms the AHP into a sustained ADP (Pressler et al 2007;Smith and Araneda 2010); the resulting synaptic potentiation requires calcium release from internal stores in the endoplasmic reticulum (Ghatpande et al 2006). In contrast, NE alters GC excitability nonmonotonically by modulating an ohmic potassium current, I KL (Nai et al 2010).…”

“…Activation of muscarinic ACh receptors (mAChRs) by the cholinergic receptor agonist carbachol (CCh) potentiates the excitability of GCs by transforming postspike AHPs into sustained ADPs (Pressler et al 2007;Smith and Araneda 2010). In addition, when the membrane potential is close to firing threshold, depolarizing inputs can produce quasipersistent firing when CCh is included in the bath solution (Pressler et al 2007).…”

“…The ADP is dependent on intracellular calcium accumulation and mediated by the Ca 2ϩ -activated nonselective cation current, I CAN (Inoue and Strowbridge 2008;Pressler et al 2007;Smith and Araneda 2010). Figure 3D illustrates the evolution of the intracellular perimembrane Ca 2ϩ concentration (Fig.…”

“…In vitro, the activation of nicotinic receptors has been shown to depolarize MCs (Castillo et al 1999;D'Souza and Vijayaraghavan 2012); earlier in vivo studies also suggested that activation of nicotinic receptors would increase firing in periglomerular cells (Ravel et al 1990), a finding that has been supported by recent slice data (D'Souza and Vijayaraghavan 2012). Muscarinic receptor activation increases the excitability of GCs by transforming a net afterhyperpolarization (AHP) following each spike into an afterdepolarization (ADP) (Pressler et al 2007;Smith and Araneda 2010). This ADP extends the period of activation of the GC, altering the balance of excitation and inhibition in the deeper bulbar layers and constraining MC action potential (AP) timing (Li and Cleland 2013;Pressler et al 2007).…”

Impact of Basal Forebrain Cholinergic Inputs on Basolateral Amygdala Neurons

“…In both the neocortex and BLA, a subpopulation of interneurons expresses muscarinic type-2 (M2) receptors (Levey et al, 1991;McDonald and Mascagni, 2011) whereas principal cells express M1 receptors (Mrzljak et al, 1993;McDonald and Mascagni, 2010;Yamasaki et al, 2010). Pharmacological activation of muscarinic receptors elicits similar responses in principal neurons of the neocortex and BLA.…”