What Does the Human Olfactory System Do, and How Does It Do It?

Historically, the human sense of smell has been regarded as the odd stepchild of the senses, especially compared to the sensory bravado of seeing, touching, and hearing. The idea that the human olfaction has little to contribute to our experience of the world is commonplace, though with the emergence of COVID-19 there has rather been a sea change in this understanding. An ever increasing body of work has convincingly highlighted the keen capabilities of the human nose and the sophistication of the human olfactory system. Here, we provide a concise overview of the neuroscience of human olfaction spanning the last 10-15 years, with focus on the peripheral and central mechanisms that underlie how odor information is processed, packaged, parceled, predicted, and perturbed to serve odor-guided behaviors. We conclude by offering some guideposts for harnessing the next decade of olfactory research in all its shapes and forms.

Odor representations from the two nostrils are temporally segregated in human piriform cortex.

The human olfactory system has two discrete channels of sensory input, arising from olfactory epithelia housed in the left and right nostrils. Here, we asked whether the primary olfactory cortex (piriform cortex [PC]) encodes odor information arising from the two nostrils as integrated or distinct stimuli. We recorded intracranial electroencephalogram (iEEG) signals directly from PC while human subjects participated in an odor identification task where odors were delivered to the left, right, or both nostrils. We analyzed the time course of odor identity coding using machine-learning approaches and found that uni-nostril odor inputs to the ipsilateral nostril are encoded ∼480-ms faster than odor inputs to the contralateral nostril on average. During naturalistic bi-nostril odor sampling, odor information emerged in two temporally segregated epochs, with the first epoch corresponding to the ipsilateral and the second epoch corresponding to the contralateral odor representations. These findings reveal that PC maintains distinct representations of odor input from each nostril through temporal segregation, highlighting an olfactory coding scheme at the cortical level that can parse odor information across nostrils within the course of a single inhalation.

Odor representations from the two nostrils are temporally segregated in human piriform cortex.

The human olfactory system has two discrete channels of sensory input, arising from olfactory epithelia housed in the left and right nostrils. Here, we asked whether primary olfactory cortex (piriform cortex, PC) encodes odor information arising from the two nostrils as integrated or distinct stimuli. We recorded intracranial EEG signals directly from PC while human subjects participated in an odor identification task where odors were delivered to the left, right, or both nostrils. We analyzed the time-course of odor-identity coding using machine learning approaches, and found that uni-nostril odor inputs to the ipsilateral nostril are encoded ~480 ms faster than odor inputs to the contralateral nostril on average. During naturalistic bi-nostril odor sampling, odor information emerged in two temporally segregated epochs with the first epoch corresponding to the ipsilateral and the second epoch corresponding to the contralateral odor representations. These findings reveal that PC maintains distinct representations of odor input from each nostril through temporal segregation, highlighting an olfactory coding scheme at the cortical level that can parse odor information across nostrils within the course of a single inhalation.

Layer- and Cell Type-Specific Response Properties of Gustatory Cortex Neurons in Awake Mice.

Studies in visual, auditory, and somatosensory cortices have revealed that different cell types as well as neurons located in different laminae display distinct stimulus response profiles. The extent to which these layer and cell type-specific distinctions generalize to gustatory cortex (GC) remains unknown. In this study, we performed extracellular recordings in adult female mice to monitor the activity of putative pyramidal and inhibitory neurons located in deep and superficial layers of GC. Awake, head-restrained mice were trained to lick different tastants (sucrose, salt, citric acid, quinine, and water) from a lick spout. We found that deep layer neurons show higher baseline firing rates (FRs) in GC with deep-layer inhibitory neurons displaying highest FRs at baseline and following the stimulus. GC's activity shows robust modulations before animals' contact with tastants, and this phenomenon is most prevalent in deep-layer inhibitory neurons. Furthermore, we show that licking activity strongly shapes the spiking pattern of GC pyramidal neurons, eliciting phase-locked spiking across trials and tastants. We demonstrate that there is a greater percentage of taste-coding neurons in deep versus superficial layers with chemosensitive neurons across all categories showing similar breadth of tuning, but different decoding performance. Lastly, we provide evidence for functional convergence in GC, with neurons that can show prestimulus activity, licking-related rhythmicity and taste responses. Overall, our results demonstrate that baseline and stimulus-evoked firing profiles of GC neurons and their processing schemes change as a function of cortical layer and cell type in awake mice.SIGNIFICANCE STATEMENT Sensory cortical areas show a laminar structure, with each layer composed of distinct cell types embedded in different circuits. While studies in other primary sensory areas have elucidated that pyramidal and inhibitory neurons belonging to distinct layers show distinct response properties, whether and how response properties of gustatory cortex (GC) neurons change as a function of their laminar position and cell type remains uninvestigated. Here, we show that there are several notable differences in baseline, prestimulus, and stimulus-evoked response profiles of pyramidal and inhibitory neurons belonging to deep and superficial layers of GC.