Norepinephrine and learning-induced plasticity in infant rat olfactory system

Abstract

Postnatal olfactory learning produces both a conditioned behavioral response and a modified olfactory bulb neural response to the learned odor. The present report describes the role of norepinephrine (NE) on both of these learned responses in neonatal rat pups. Pups received olfactory classical conditioning training from postnatal days (PN) 1-18. Training consisted of 18 trials with an intertrial interval of 24 hr. For the experimental group, a trial consisted of a pairing of unconditioned stimulus (UCS, stroking/tactile stimulation) and the conditioned stimulus (CS, odor). Control groups received either only the CS (Odor only) or only the UCS (Stroke only). Within each training condition, pups were injected with either the NE beta-receptor agonist isoproterenol (1, 20, or 4 mg/kg), the NE beta-receptor antagonist propranolol (10, 20, 40 mg/kg), or saline 30 min prior to training. On day 20, pups received one of the following tests: (1) behavioral conditioned responding, (2) injection with 14C-2-deoxyglucose (2-DG) and exposed to the CS odor, or (3) tested for olfactory bulb mitral/tufted cell single-unit responses to the CS odor. The results indicated that training with either: (1) Odor-Stroke-Saline, (2) Odor-Stroke-Isoproterenol-Propranolol, or (3) Odor only-Isoproterenol (2 mg/kg) was sufficient to produce a learned behavioral odor preference, enhanced uptake of 14C-2-DG in the odor-specific foci within the bulb, and a modified output signal from the bulb as measured by single-cell recordings of mitral/tufted cells. Moreover, propranolol injected prior to Odor-Stroke training blocked the acquisition of both the learned behavior and olfactory bulb responses. Thus, NE is sufficient and may be necessary for the acquisition of both learned olfactory behavior and olfactory bulb responses.

pCREB in the Neonate Rat Olfactory Bulb Is Selectively and Transiently Increased by Odor Preference–Conditioned Training

“…The pups in the present experiment were subjected to training procedures but were not tested for recall because we wished to examine the role of pCREB specifically in the acquisition of olfactory learning. In previous studies, we (McLean et al 1993(McLean et al , 1996Langdon et al 1997;Price et al 1998), as well as others Leon 1986a, 1987;Sullivan et al 1989aSullivan et al , 1991, have shown that pups subjected to the different training procedures show predictable behavioral outcomes.…”

“…While the selectivity of the pCREB increase for the pairing condition supports a special role of the CREB promoter in associative learning, future investigations should compare forward (Odor + Stroking) and backward (Stroking followed by Odor, nonlearning) pairing. A demonstration of an effect of pairing order, which is known to affect memory formation in this paradigm (McLean et al 1996;Sullivan and Hall 1988;Sullivan et al 1991;Sullivan et al 1989b;Wilson and Sullivan 1991), would provide the strongest test of the claim for a unique association between pCREB increases and associative memory formation.…”

“…Stroking of a pup is known to activate cells of the noradrenergic locus coeruleus (Nakamura et al 1987) and an olfactory preference is conditioned in neonate rats by pairing stroking with a novel odor Leon 1986b, 1987). The acquisition of a preference for the novel odor requires activation of ␤ adrenoceptors in the rat olfactory bulb (Sullivan et al 1989a). Thus, the odor conditioning is dependent on a noradrenergic unconditioned stimulus signal coupled to cAMP increases which could initiate CREB phosphorylation through translocation of the catalytic subunit of protein kinase A.…”

Locus Ceruleus Activation Initiates Delayed Synaptic Potentiation of Perforant Path Input to the Dentate Gyrus in Awake Rats: A Novel β-Adrenergic- and Protein Synthesis-Dependent Mammalian Plasticity Mechanism

“…LC activation paired with sensory input does produce longterm memory in some paradigms (Sullivan et al, 1989). In rat pup olfactory preference learning, ␤-adrenoceptor stimulation in the olfactory bulb paired with glutamatergic input from olfactory neurons produces an odor preference 24 hr later (Sullivan et al, 2000).…”

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).…”