The Mammalian Olfactory Bulb Contributes to the Adaptation of Odor Responses: A Second Perceptual Computation Carried Out by the Bulb

Abstract

While humans and other mammals exhibit adaptation to odorants, the neural mechanisms and brain locations involved in this process are incompletely understood. One possibility is that it primarily occurs as a result of the interactions between odorants and odorant receptors on the olfactory sensory neurons in the olfactory epithelium. In this scenario, adaptation would arise as a peripheral phenomenon transmitted to the brain. An alternative possibility is that adaptation occurs because of processing in the brain. We made an initial test of these possibilities using a two-color imaging strategy to simultaneously measure the activity of the olfactory receptor nerve terminals (input to the bulb) and mitral/tufted cell apical dendrites (output from the bulb) in anesthetized and awake mice. Repeated odor stimulation at the same concentration resulted in a decline in the bulb output, while the input remained relatively stable. Thus, the mammalian olfactory bulb appears to participate in generating the perception of olfactory adaptation under this stimulus condition. Similar experiments conducted previously showed that the bulb may also participate in the perception of concentration invariance of odorant recognition ( Storace and Cohen, 2017 ); thus, the bulb is simultaneously carrying out more than one computation, as is true of other mammalian brain regions and perhaps is the case for all animals with sophisticated nervous systems. However, in contrast with other sensory systems ( Van Essen et al., 1992 ), the very first processing stage in the olfactory system has an output that may directly represent perceptions.

Voltage imaging in the olfactory bulb using transgenic mouse lines expressing the genetically encoded voltage indicator ArcLight

“…These results are consistent with prior reports using calcium sensitive sensors indicating that olfactory receptor neurons exhibit adaptation at very high odor concentrations but recover in response to odor stimuli at lowto-moderate concentrations with interstimulus intervals of 6 seconds 39,40,42,43 .…”

“…and D.A.S., preliminary results). In another comparison, the olfactory bulbs of anesthetized and awake mice had similar adaptation properties 42 . Overall, additional awake-anesthetized comparisons may prove informative.…”

“…Thus, the OMP-ArcLight transgenic line represents the first in vivo measurements of membrane potential changes from olfactory receptor neuron glomeruli in mice. Because previous measurements of the odorant concentration dependence and adaptation in olfactory receptor neurons had been carried out with calcium sensitive indicators 11,33,34,42 , there was concern that those results might depend on the use of calcium as a surrogate for action potential activity. Using the OMP-ArcLight mice, we found that the voltage indicator results (Figs.…”

Genetics, molecular control and clinical relevance of habituation learning

“…Here, each sensory channel can contribute to multiple sensory percepts, whereas synaptic depression of sensory axon terminals cannot not explain stimulus specificity. Accordingly, the activity of inhibitory neurons shapes stimulus responses and habituation in the mammalian olfactory bulb (Koulakov and Rinberg, 2011;Storace and Cohen, 2021). Inhibitory potentiation may thus represent a conserved mediator of habituation -the 'habituation element' -widely operating across species and in numerous paradigms.…”

Genetics, Molecular Control and Clinical Relevance of Habituation Learning

“…Inhibitory potentiation can better explain habituation characteristics that are difficult to reconcile with homosynaptic depression, including dishabituation, long-term habituation, and more effective habituation with weak stimuli. The activity of inhibitory neurons also shapes stimulus responses and habituation in the mammalian olfactory bulb [61,62]. Inhibitory potentiation may thus represent a key mediator of habituation -the 'habituation element'widely operating across species and paradigms.…”