Olfactory Coding and Decoding by Ensembles of Neurons
- Mark Stopfer, PhD, Head, Section on Sensory Coding and Neural Ensembles
- Zane Aldworth, PhD, Staff Scientist
- Yu-Shan Hung, PhD, Postdoctoral Fellow
- Subhasis Ray, PhD, Postdoctoral Fellow
- Kazumichi Shimizu, PhD, Postdoctoral Fellow
- Kui Sun, MD, Technician
All animals need to know what is going on in the world around them. Brain mechanisms have thus evolved to gather and organize sensory information in order to build transient and sometimes enduring internal representations of the environment. Using relatively simple animals and focusing primarily on olfaction and gustation, we combine electrophysiological, anatomical, behavioral, computational, genetic, and other techniques to examine the ways in which intact neural circuits, driven by sensory stimuli, process information. Our work reveals basic mechanisms by which sensory information is transformed, stabilized, and compared, as it makes its way through the nervous system.
Neural encoding of odors during active sampling and in turbulent plumes
An important feature of sensory modalities is that natural sensory stimuli can be distorted by environmental or active events leading, for example, to stimulus intermittency. Passive causes of olfactory intermittency include air or water turbulence, breaking up, for example, an odor plume into concentrated packets, or filaments of odor separated by pockets of very low odor concentration. The second cause is self-generated or active and results from the animal's own sampling behaviors, including sniffing in mammals and olfactory appendage flicking in crustaceans and insects. Little is known about how neural circuits encode the resulting stimuli or about the behaviors animals use to interact with them.
To evaluate the effects of stimulus variability caused by odor plume turbulence and active sampling, we developed two novel experimental paradigms with locusts to isolate and characterize the two causes of intermittency. With a fixed-antenna wind-tunnel preparation, we could investigate neural coding features elicited by chaotic, natural odor plumes. Despite their irregularity, chaotic odor plumes still drove dynamic neural response features including the synchronization, temporal patterning, and short-term plasticity of spiking in projection neurons, enabling classifier-based stimulus identification and activating downstream decoders (Kenyon cells). With an active-sampling preparation, in which locusts were free to flick their antenna through a linear odor filament and walk freely on a substrate, we could combine behavioral analyses with electrophysiology to address the functional significance of self-induced stimulus intermittency for olfactory coding. Odors triggered immediate, spatially targeted antennal scanning that, paradoxically, weakened individual neural responses. However, these frequent but weaker responses were highly informative about stimulus location.
Our results show that spatio-temporally structured neural responses efficiently encode naturally chaotic and intermittent olfactory stimuli and that active sampling behaviors take advantage of this ability by increasing intermittency to gain more information about an odor’s location.
Identified gustatory second-order neuron in the Drosophila brain
Little is known, in any species, about neural circuitry immediately following gustatory sensory neurons, which makes it difficult to know how gustatory information is processed by the brain. By genetically labeling and manipulating specific parts of the nervous system, we identified and characterized a bilateral pair of gustatory second-order neurons in Drosophila. Previous studies had already identified gustatory sensory neurons that relay information to distinct parts of the gnathal (sub-esophageal) ganglia. To identify candidate gustatory second-order neurons, we took an anatomical approach. We screened about 5,000 GAL4 driver strains for lines that label neural fibers innervating the gnathal ganglia. We then combined GRASP (GFP reconstitution across synaptic partners) with presynaptic labeling to visualize potential synaptic contacts between the dendrites of the candidate gustatory second-order neurons and the axonal terminals of Gr5a–expressing sensory neurons, which have been shown to respond to sucrose. Results of the GRASP analysis, followed by a single-cell analysis by FLP-out recombination, identified a specific pair of neurons that contact Gr5a axon terminals in both brain hemispheres and send axonal arborizations to a distinct region within the gnathal ganglia. To characterize the input and output branches, respectively, we expressed the fluorescence-tagged acetylcholine receptor subunit (Da7) and active-zone marker (Brp) in the gustatory second-order neurons.
We found that input sites of the gustatory second-order neurons overlaid GRASP–labeled synaptic contacts to Gr5a neurons, while presynaptic sites were broadly distributed throughout the neurons’ arborizations. GRASP analysis and further tests with a new version of GRASP that labels active synapses suggested that the identified second-order neurons receive synaptic inputs from Gr5a–expressing sensory neurons, but not from Gr66a–expressing sensory neurons, which respond to caffeine. The identified second-order neurons relay information from Gr5a–expressing sensory neurons to stereotypical regions in the gnathal ganglia. Our findings suggest an unexpected complexity for taste-information processing in the first relay of the gustatory system. We are presently following up on this work to identify additional second-order neurons and, with optical imaging and intracellular electrophysiology experiments, to characterize their functions and information-coding strategies.
Spatiotemporal coding of individual chemicals by the gustatory system
Four of the five major sensory systems (vision, olfaction, somatosensation, and audition) are thought to be encoded by spatio-temporal patterns of neural activity. The only exception is gustation. Gustatory coding by the nervous system is thought to be relatively simple: every chemical (‘tastant’) is associated with one of a small number of basic tastes, and the presence of a basic taste, rather than the specific tastant, is represented by the brain. In mammals as well as insects, five basic tastes are usually recognized: sweet, salty, sour, bitter, and umami. The neural mechanism for representing basic tastes is unclear. The most widely accepted proposal is that, in both mammals and insects, gustatory information is carried through labelled lines: separate channels, from the periphery to sites deep in the brain, of cells sensitive to a single basic taste. An alternate proposal is that the basic tastes are represented by populations of cells, with each cell sensitive to multiple basic tastes.
Testing these ideas requires determining, point-to-point, how tastes are initially represented within the population of receptor cells and how this representation is transformed as it moves to higher-order neurons. However, it has been highly challenging to deliver precisely timed tastants while recording cellular activity from directly connected cells at successive layers of the gustatory system. Using a new moth preparation, we designed a stimulus and recording system that allowed us to fully characterize the timing of tastant delivery and the dynamics of the tastant-elicited responses of gustatory receptor neurons and their mono-synaptically connected second-order gustatory neurons, before, during, and after tastant delivery.
Surprisingly, we found no evidence consistent with a basic taste model of gustation. Instead, we found that the moth’s gustatory system represents individual tastant chemicals as spatio-temporal patterns of activity distributed across the population of gustatory receptor neurons. Further, we found that the representations are transformed substantially as many types of gustatory receptor neurons converge broadly upon follower neurons. The results of our physiological and behavioral experiments suggest that the gustatory system encodes information not about basic taste categories but rather about the identities of individual tastants. Further, the information is carried not by labelled lines but rather by distributed, spatio-temporal activity, which is a fast and accurate code. The results provide a dramatically new view of taste processing.
Tradeoff between information format and capacity in the olfactory system
How does the nervous system ‘decide’ what format to use to encode information? The brain’s internal representation of the environment is built from patterns of neural activity bearing information about sensory stimuli. As this activity travels through the brain, a succession of neural circuits manipulates it into a series of coding formats, each thought to provide specific advantages for processing information. Each coding format has, however, advantages and disadvantages. How the benefits of a given format are balanced against its costs is largely unknown.
One common coding format uses periodic inhibition to coordinate neural spiking into synchronous oscillations. It has been proposed that oscillatory synchrony offers several benefits, including enhancing the discriminability of sensory representations and ‘binding’ diverse stimulus features into coherent percepts. We examined how neural oscillatory synchronization affects another measure of coding quality: the rate at which information is transmitted. We evaluated this potential tradeoff between coding format and information rate in the olfactory system of the locust. To test the possible tradeoffs imposed by synchrony, we needed a richly structured olfactory stimulus appropriate for the measurement of information properties. We decided to focus on stimulus timing because we could provide, with a synthetic odor plume, a broad sample of an environmentally meaningful stimulus space. Using artificial plumes based on the statistical structures of temporal variability measured outdoors in real odor plumes allowed us to calculate lower bound estimates of information in the temporal structure of an ethologically relevant stimulus. Thus, we delivered odorants as controlled, repeatable plumes while recording responses from populations of projection neurons as they transmitted information about the plume’s temporal structure. We evaluated the information content of neurons in terms of the mutual information rate between the temporal dynamics of the odorant stimulus and the neuronal response by finding the difference between the unconditional and stimulus-conditioned response entropies.
Surprisingly, our results showed that pharmacologically blocking synchronization by locally injecting picrotoxin led to a significant increase in information rate. Thus, the use of a synchronous coding scheme introduces a tradeoff: synchrony allows correlation coding and fine olfactory discrimination; however, by reducing the number of spikes and spike positions available for encoding information, synchrony also reduces the ability of the system to rapidly transmit information about the stimulus. The inhibition-induced reduction in transmission capacity that we observed in the olfactory system likely occurs in any neural circuit using periodic inhibition. Our results suggest that reformatting to an oscillatory structure comes at a cost and thus represents a fundamental tradeoff between coding capacity and other aspects of format utility.
Additional Funding
- NICHD Director's Award for a collaborative grant written by Mark Stopfer and Chi-Hon Lee.
Publications
- Reiter S, Campillo Rodriguez C, Sun K, Stopfer M. Spatiotemporal coding of individual chemicals by the gustatory system. J Neurosci 2015;35:12309-12321.
- Huston SJ, Stopfer M, Cassenaer S, Aldworth ZN, Laurent G. Neural encoding of odors during active sampling and in turbulent plumes. Neuron 2015;88:1-16.
- Aldworth Z, Stopfer M. Tradeoff between information format and capacity in the olfactory system. J Neurosci 2015;35:1521-1529.
- Miyazaki T, Lin TY, Ito K, Lee CH, Stopfer M. A gustatory second-order neuron that connects sucrose-sensitive primary neurons and a distinct region of the gnathal ganglion in the Drosophila brain. J Neurogenet 2015;29(2-3):144-155.
- Kee T, Sanda P, Gupta N, Stopfer M, Bazhenov M. Feed-forward versus feedback inhibition in a basic olfactory circuit. PLoS Comput Biol 2015;11:e1004531.
Collaborators
- Maxim Bazhenov, PhD, Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA
- Kei Ito, PhD, University of Tokyo, Tokyo, Japan
- Gilles Laurent, DVM, PhD, Director, Max Planck Institute for Brain Research, Frankfurt/Main Germany
- Chi-Hon Lee, MD, PhD, Section on Neuronal Connectivity, NICHD, Bethesda, MD
Contact
For more information, email stopferm@mail.nih.gov or visit https://neuroscience.nih.gov/Faculty/Profile/mark-stopfer.aspx or https://irp.nih.gov/pi/mark-stopfer.
