Dopamine D2 Receptor–Mediated Presynaptic Inhibition of Olfactory Nerve Terminals

Abstract

Olfactory receptor neurons of the nasal epithelium project via the olfactory nerve (ON) to the glomeruli of the main olfactory bulb, where they form glutamatergic synapses with the apical dendrites of mitral and tufted cells, the output cells of the olfactory bulb, and with juxtaglomerular interneurons. The glomerular layer contains one of the largest population of dopamine (DA) neurons in the brain, and DA in the olfactory bulb is found exclusively in juxtaglomerular neurons. D2 receptors, the predominant DA receptor subtype in the olfactory bulb, are found in the ON and glomerular layers, and are present on ON terminals. In the present study, field potential and single-unit recordings, as well as whole cell patch-clamp techniques, were used to investigate the role of DA and D2 receptors in glomerular synaptic processing in rat and mouse olfactory bulb slices. DA and D2 receptor agonists reduced ON-evoked synaptic responses in mitral/tufted and juxtaglomerular cells. Spontaneous and ON-evoked spiking of mitral cells was also reduced by DA and D2 agonists, and enhanced by D2 antagonists. DA did not produce measurable postsynaptic changes in juxtaglomerular cells, nor did it alter their responses to mitral/tufted cell inputs. DA also reduced 1) paired-pulse depression of ON-evoked synaptic responses in mitral/tufted and juxtaglomerular cells and 2) the amplitude and frequency of spontaneous, but not miniature, excitatory postsynaptic currents in juxtaglomerular cells. Taken together, these findings are consistent with the hypothesis that activation of D2 receptors presynaptically inhibits ON terminals. DA and D2 agonists had no effect in D2 receptor knockout mice, suggesting that D2 receptors are the only type of DA receptors that affect signal transmission from the ON to the rodent olfactory bulb.

Olfactory Bulb Glomeruli: External Tufted Cells Intrinsically Burst at Theta Frequency and Are Entrained by Patterned Olfactory Input

“…At all frequencies, there was a decrement in burst amplitude from the first to the second stimulus. This is to be expected because of the fact that ON terminals are subject to presynaptic inhibition following a single ON stimulus (Aroniadou-Anderjaska et al, 2000;Ennis et al, 2001). Notwithstanding this paired-pulse decrement, the ET cell bursts were readily entrained to 5 Hz ON stimuli.…”

G o α regulates olfactory adaptation by antagonizing G q α-DAG signaling in Caenorhabditis elegans

“…Instead, GOA-1 appears to be activated in response to prolonged or strong odor stimuli. In the olfactory bulb, olfactory receptor neurons (ORNs) are thought to be presynaptically inhibited by GABA and dopamine released by juxtaglomerular cells, which receive excitatory glutamatergic input from ORNs in the glomeruli (47)(48)(49)(50). By analogy, interneurons located downstream of AWC neurons in C. elegans may release an inhibitory signal to repress activity of AWC neurons during olfactory adaptation, and this inhibitory signal may be transmitted by GOA-1 in AWC neurons.…”

Olfactory Bulb External Tufted Cells Are Synchronized by Multiple Intraglomerular Mechanisms

“…PG cells, which are activated by ET cell bursts (Hayar et al, 2004a), provide synchronous inhibitory feedback to ET cells, thereby creating a refractory period during which the glomerulus is less responsive to sensory input. GABA and dopamine released by PG cells also causes presynaptic inhibition of ON terminals, which augments the refractory period generated by the ET-PG-ET circuit (Ennis et al, 2001;Wachowiak et al, 2005). Thus, the intraglomerular circuit may function first to amplify olfactory nerve input and then to generate a refractory window, within which sensory inputs are integrated to synchronize glomerular output.…”