Theta bursts in the olfactory nerve paired with β-adrenoceptor activation induce calcium elevation in mitral cells: A mechanism for odor preference learning in the neonate rat

Abstract

Odor preference learning in the neonate rat follows pairing of odor input and noradrenergic activation of b-adrenoceptors. Odor learning is hypothesized to be supported by enhanced mitral cell activation. Here a mechanism for enhanced mitral cell signaling is described. Theta bursts in the olfactory nerve (ON) produce long-term potentiation (LTP) of glomerular excitatory postsynaptic potentials (EPSPs) and of excitatory postsynaptic currents (EPSCs) in the periglomerular (PG) and external tufted (ET) cells. Theta bursts paired with b-adrenoceptor activation significantly elevate mitral cell (MC) calcium. Juxtaglomerular inhibitory network depression by b-adrenoceptor activation appears to increase calcium in MCs in response to theta burst stimulation.Early odor preference learning provides us with a model in which the necessary and sufficient inputs for learning can be localized to a relatively simple cortical structure, the olfactory bulb (Sullivan et al. 2000). The critical changes for this natural form of learning occur in the olfactory bulb network (Coopersmith and Leon 1986, 1995Wilson et al. 1987;Woo et al. 1987;Wilson and Leon 1988; Wilson and Leon 1991;Guthrie et al. 1993;Johnson et al. 1995;Yuan et al. 2002). Odor preference learning is induced by the pairing of odor with activation of the locus coeruleus noradrenergic system, a component of our arousal circuitry (Harley 1987;Berridge and Waterhouse 2003;Berridge 2008), which is critically involved in other forms of memory (Harley 1987;Berridge and Waterhouse 2003) and compromised in diseases of memory, such as Alzheimer's (Palmer and DeKosky 1993;Weinshenker 2008). The unconditioned stimulus for early odor preference learning is mediated by b-adrenoceptor activation in the olfactory bulb (Sullivan et al. , 1992 Sullivan 1991, 1994;Harley et al. 2006). b-Adrenoceptor agonists and antagonists infused in the olfactory bulb can induce or block learning, respectively (Sullivan et al. 1989(Sullivan et al. , 2000.Despite the fact that the behavioral model for early odor preference learning has been established for decades (Sullivan et al. 1988(Sullivan et al. , 1989, and despite the fact that the olfactory bulb circuit contains synapses that are essential for the formation of a localizable long-term memory that is easily indexed in behavior (Coopersmith and Leon 1986;Wilson et al. 1987;Woo et al. 1987;Wilson and Leon 1988;Woo and Leon 1991;Johnson et al. 1995;McLean et al. 1999;Yuan et al. 2002), the circuitry and the synapses in the olfactory bulb that mediate learning are not well understood. Long-term potentiation (LTP), the putative synaptic model for associative learning in other brain regions (Bliss and Lomo 1973;Brown et al. 1988;Barnes 1995;Malenka 1994), has not been demonstrated compellingly in the rat olfactory bulb. The lack of evidence for a synaptic locus and a mechanism to support odor preference learning is partly due to the dissociation of the neural changes previously observed following early odor learning (seen at the glomerular input level...

Age-dependent adrenergic actions in the main olfactory bulb that could underlie an olfactory-sensitive period

“…These gamma oscillations reflect dendrodendritic synaptic interactions between GABAergic granule cells (GCs) and output mitral cells (MCs) (Rall and Shepherd 1968), and their long-lasting enhancement could modify integration of MC inputs by downstream olfactory cortical structures (Mori et al 1999). NE through ␤-AR activation can also elicit long-lasting increases in MC excitatory responses following olfactory nerve (ON) stimulation in very young rats (Lethbridge et al 2012;Yuan 2009;Yuan et al 2000). In terms of acute effects, NE can reduce inhibitory GC-to-MC transmission in rodents less than P14 (Pandipati et al 2010; Wilson and Leon 1988).…”

Adrenergic Receptor-Mediated Disinhibition of Mitral Cells Triggers Long-Term Enhancement of Synchronized Oscillations in the Olfactory Bulb

“…Besides causing disinhibition at GC-to-MC synapses, acute exposure of the bulb to NE can cause direct excitation of MCs via ␣ 1 AR-mediated closure of potassium channels as well as specific changes in glomeruli that are mediated by ␤ ARs (enhanced excitatory transmission from ON terminals and depression of juxtaglomerular cell inhibition) (Yuan 2009;Yuan et al 2000). To address whether disinhibition at GC-to-MC synapses accounts for the NEinduced long-term enhancement of the synchronized oscillations, we first examined whether the ␣ 2 AR-specific agonist clonidine, which causes disinhibition, could mimic NE in causing the long-term effect.…”

α2-Adrenergic receptor activation promotes long-term potentiation at excitatory synapses in the mouse accessory olfactory bulb

“…Enhanced release of noradrenaline (NA) within the MOB plays an important role in long-term synaptic plasticity and odor learning in a variety of contexts. These include olfactory conditioning in neonatal rats (Sullivan et al 1989(Sullivan et al , 1992(Sullivan et al , 2000Harley et al 2006;Zhang et al 2010;Shakhawat et al 2012), the learning of newborn lamb odors after parturition in sheep (Pissonnier et al 1985), odor discrimination after memory formation in mice (Doucette et al 2007;Shea et al 2008;Moreno et al 2012), a specific long-term suppression of mitral cell (MC) responses to paired odors in mice (Shea et al 2008), a long-term reduction of paired-pulse inhibition in neonatal rats (Wilson and Leon 1988), long-term enhancement of synchronized γ frequency oscillations in rat MOB slices (Gire and Schoppa 2008;Pandipati et al 2010), long-term potentiation (LTP) of synaptic strength in rat MOB slices (Yuan 2009;Zhang et al 2010), and a long-term suppression of presynaptic input to MCs in mice (Eckmeier and Shea 2014).…”