Stressors impair odor recognition memory via an olfactory bulb-dependent noradrenergic mechanism

Abstract

Non-associative habituation and odor recognition tasks have been widely used to probe questions of social recognition, odor memory duration, and odor memory specificity. Among others, these paradigms have provided valuable insight into how neuromodulation, and specifically norepinephrine/noradrenaline (NE) influences odor memory. In general, NE levels are modulated by arousal, stress, and behavioral state, but there is sparse evidence of a direct relationship between NE and odor memory in adult rodents. The present study uses simple mild psychological stressors (bright light and sound) to modulate NE levels physiologically in order to probe stressors NE-dependent effect on odor recognition memory. In rats with bilateral bulbar cannulations, we show that these stressors modulate olfactory memory and that this effect is at least partially mediated by the olfactory bulb. Specifically, we show that the presence of stressors during the acquisition of odor memory suppresses memory for an odor when tested 30 min after familiarization to that odor. This suppression is blocked by infusing NE antagonists into the olfactory bulb prior to odor acquisition. Additionally, we find that infusion of bulbar NE is sufficient to suppress odor memory in a manner mimicking that of our stressors. These effects are unlikely to be solely mediated by locomotor/exploratory changes produced by stressors, although these stressors influence certain behaviors not directly related to odor investigation. This study provides important information about how behaviorally relevant changes in NE can influence top-down sensory processing and odor memory.

Norepinephrine, olfactory bulb and memory stability

“…A computational model incorporating known cellular and network effects of NE in the OB suggests that NE modulation of OB dynamics are mediating these effects. Interestingly we do not observe acute effects of lacking NE activity during learning, but see significant effects of this temporary manipulation long after the manipulation has stopped, which can underlie observations with respect to NE and stress in the OB (Manella et al, 2013) and NE and integration of adult born neurons into the network (Moreno et al, 2012).…”

Construction of Odor Representations by Olfactory Bulb Microcircuits

“…Initial physiological studies of these neurons had indicated that they were glutamatergic and excitatory (Aungst et al, 2003); however, subsequent studies demonstrated that they are GABAergic and dopaminergic (Liu et al, 2013), and indeed probably constitute one extreme of a single morphologically heterogeneous class of interneurons that includes periglomerular cells (Kiyokage et al, 2010;McGann, 2013;Sethupathy et al, 2013). This is interesting because recent work has shown that, despite their GABAergic phenotype, sSA cells are clearly the effectors of a functionally excitatory lateral network that results in the broad and graded inhibition of mitral cells (Marbach and Albeanu, 2011). This lateral excitatory effect across the sSA network potentially could arise via gap-junction coupling among sSA and periglomerular cells, or by rendering GABAergic synapses onto periglomerular and sSA cells excitatory owing to a reversed chloride gradient in these neurons.…”

Habituation mechanisms and their importance for cognitive function

“…These mechanisms lead to sensory filtering and habituation of perception. Manella et al ( 2013 ) studied how the modulatory norepinephrine system in the brain influences odor habituation and odor memory in rats.…”