Olfactory bulb acetylcholine release dishabituates odor responses and reinstates odor investigation

Abstract

Habituation and dishabituation modulate the neural resources and behavioral significance allocated to incoming stimuli across the sensory systems. We characterize these processes in the mouse olfactory bulb (OB) and uncover a role for OB acetylcholine (ACh) in physiological and behavioral olfactory dishabituation. We use calcium imaging in both awake and anesthetized mice to determine the time course and magnitude of OB glomerular habituation during a prolonged odor presentation. In addition, we develop a novel behavioral investigation paradigm to determine how prolonged odor input affects odor salience. We find that manipulating OB ACh release during prolonged odor presentations using electrical or optogenetic stimulation rapidly modulates habituated glomerular odor responses and odor salience, causing mice to suddenly investigate a previously ignored odor. To demonstrate the ethological validity of this effect, we show that changing the visual context can lead to dishabituation of odor investigation behavior, which is blocked by cholinergic antagonists in the OB.

Cortical Microcircuit Mechanisms of Mismatch Negativity and Its Underlying Subcomponents

“…The local inhibition accounts for a significant proportion of SSA but cannot completely explain the altered neural responses (Ayala and Malmierca, 2018), indicating other mechanisms play a role as well. Similarly, cholinergic and endocannabinoid systems act to modulate SSA subcortical auditory and olfactory responses en masse but are not responsible for generating SSA Valdés-Baizabal et al, 2017;Ogg et al, 2018). Iontophoretic application of both acetylcholine and cannabinoid agonists appear to increase responses (through muscarinic receptors and cannabinoid receptors type 1, respectively) specifically to repetitive stimulations, thereby reducing SSA, without affecting neural responses to the deviant tone Valdés-Baizabal et al, 2017).…”

“…All together these effects likely propagate to downstream primary cortices, thus altering the input to these regions in a stimulus specific manner and driving behavioral responses. There is indirect evidence to suggest that this is the case as stimulation of cholinergic release in the olfactory bulb is sufficient to reinstate olfactory bulb responses to repetitive stimuli (in both anesthetized and awake conditions) and is sufficient to reinstate behavioral investigatory behaviors to repetitive olfactory stimuli (Ogg et al, 2018); however, it remains unclear the extent to which these processes directly contribute to SSA in primary sensory cortices to contribute to cortical SSA and perceptual adaptation.…”

Complex neural representation of odour information in the olfactory bulb

“…It is important to note that all of these studies were performed on anaesthetized animals; how the neurons of the OB are modulated by cholinergic input in awake, behaving animals remains an open question. Interestingly, a recent study has demonstrated that Ach released to the OB during the prolonged odour stimulation modulated habituated odour responses and odour salience, and further caused mice to suddenly investigate a previous ignored odour, indicating the importance of Ach in the process of odour habituation and dishabituation . In addition to cholinergic input from the HDB, some cholinergic interneurons have been found in both the main and the accessory olfactory bulbs .…”

Input dependent modulation of olfactory bulb activity by GABAergic basal forebrain projections

“…Cholinergic neuromodulatory systems are thought to enhance sensory processing and amplify the signal-to-noise ratio of relevant responses 2-5 e.g. the running-induced gain increases evident in sensory cortex 6,7 or the dishabituation of odor responses in the olfactory system 8 . Furthermore, they have been identified as key players in mediating attentional modulation of sensory processing as well as in coordinating cognitive operations 9,10 .…”

“…Though only about one fifth of BF neurons are cholinergic 25 studies on olfactory processing have mainly focused on cholinergic effects 8,[27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] . In in vivo studies a specific activation of cholinergic HDB cell bodies was shown to inhibit spontaneous mitral tufted cell activity 27 while optogenetically activating cholinergic axons directly in the OB added an excitatory bias to OB output neurons: the enhancement of mitral/tufted cell odorant responses occurred independent of the strength or even polarity of the odorant-evoked response 28 .…”