Recently, our laboratory has been focused on temporal aspects of olfactory coding. We discovered that a) olfactory neuronal code at the level of olfactory bulb is temporally very precise (~10 ms) [Shusterman-2011], and b) the mammalian olfactory system can read and interpret temporal patterns at this time scales [Smear-2011]. Our efforts are directed towards establishing causal connection between neuronal coding and animal behavior.
Our lab is moving to the Neuroscience Institute at NYU Medical School in September 2012.
We are looking for a few motivated postdocs to join us in NYC.
The power of combining psychophysical and neurophysiological methods has been demonstrated in the study of visual information processing, especially in primates. As a model organism, mice enable us to use modern genetic tools to monitor, modify, and control brain circuits. Using a mouse to study sensory information processing leads naturally to focusing on olfaction because of its high relevance to rodent behavior.
Mammals sense odors through a large number of olfactory receptor neurons in olfactory epithelium. Each sensory neuron expresses one and only one gene out of a large family of olfactory receptor genes (~1200 genes in mice), but all axons of the receptor neurons, which express the same gene, converge into one or two small areas in the olfactory bulb, called glomerulus. Mitral/tufted cells, the first recipient of odor information after receptors, take their inputs from the glomerulus and send an axon to the olfactory cortices and other brain areas via the lateral olfactory tract. We are interested in the coding of olfactory information at the level of mitral/tufted cells.
What does a nose tell the brain? In our previous work, we found a striking difference in odor responses between the awake and anesthetized state (Rinberg, et.al., 2006). The spontaneous activity of mitral cells in the awake mouse is significantly higher compared to that in anesthetized mice, and odor responses are significantly smaller on the background of spontaneous activity. How are odors represented by activity of mitral/tufted cells in the olfactory bulb of awake mouse? To answer this question we need to precisely control the stimulus and monitor the behavior that follows. Our recent experiments demonstrated that neuronal response of mitral/tufted cells are locked to the sniffing/breathing pattern with very high temporal precision of ~10 ms. (Shusterman, et.al., 2011). The olfactory code at the level of the mitral/tufted cells is temporally and spatially very diverse. One odor is represented by activity of many cells and each cell exhibits temporally diverse patterns of excitation and inhibition in response to odors.
Temporal locking of olfactory responses to the phase of the sniffing cycle constitutes coding invariance in respect to the frequency of animal breathing/sniffing. Humans can identify odors independently of how fast they inhale an odor, which may be explained by observed coding invariance. The current work in the lab is directed towards understanding concentration invariance: an odor identity is independent of its concentration.
What are the features of this code that are used to produce behavior related to olfactory input? To approach this question we developed behavioral/electrophysiological paradigms to confine the features important for behavior temporally and spatially. In collaboration with Thomas Bozza (Northwestern University), we developed transgenic mice, which express Channel Rhodopsin in all olfactory receptors and in one class of olfactory receptor neurons. The opto-genetic approach allows us to control the stimulus precisely in time, by using temporally well-defined light stimulation, and in space by exciting a single glomerulus in mouse olfactory bulb.
Using opto-genetics allowed us to decouple olfactory stimulation and mouse sniffing. By illuminating epithelium in mouse nose via optical fiber, we are able to present spatially identical and temporally confined stimulus to the mouse olfactory system. This allows us to study the perception of a single stimulus cue, the timing relative to the sniff cycle, sniff phase. We found that mice can discriminate light-evoked input that is shifted in the sniff cycle by as little as 10 ms [Smear-2011].
Experiments with single glomerulus excitation are directed toward understanding the role of a single channel of information, one receptor type, in the distributed coding of olfactory stimulus.
Combining optogentic stimulation with electrophysiology and behavior allows us to dissect complex problem of olfactory perception into smaller features, and gain understanding of how these features are represented and processed in the brain.
- mouse olfactory genetics
- data analysis
- human psychophysics data analysis
- human psychophysics
- mouse/rat behavior
- modeling of air flow dynamics in the mouse nose
Comparing thoracic and intra-nasal pressure transients to monitor active odor sampling during odor-guided decision making in the mouse.Journal of neuroscience methods 2014
J. Reisert, G. J. Golden, K. Matsumura, M. Smear, D. Rinberg, and A. Gelperin Journal of neuroscience methods, 221:8-14 (2014)
BACKGROUND: Recording of physiological parameters in behaving mice has seen an immense increase over recent years driven by, for example, increased miniaturization of recording devices. One parameter particularly important for odorant-driven behaviors is the breathing frequency, since the latter dictates the rate of odorant delivery to the nasal cavity and the olfactory receptor neurons located therein. NEW METHOD: Typically, breathing patterns are monitored by either measuring the breathing-induced temperature or pressure changes in the nasal cavity. Both require the implantation of a nasal cannula and tethering of the mouse to either a cable or tubing. To avoid these limitations we used an implanted pressure sensor which reads the thoracic pressure and transmits the data telemetrically, thus making it suitable for experiments which require a freely moving animal. RESULTS: Mice performed a Go/NoGo odorant-driven behavioral task with the implanted pressure sensor, which proved to work reliably to allow recording of breathing signals over several weeks from a given animal. COMPARISON TO EXISTING METHOD(S): We simultaneously recorded the thoracic and nasal pressure changes and found that measuring the thoracic pressure change yielded similar results compared to measurements of nasal pressure changes. CONCLUSION: Telemetrically recorded breathing signals are a feasible method to monitor odorant-guided behavioral changes in breathing rates. Its advantages are most significant when recording from a freely moving animal over several weeks. The advantages and disadvantages of different methods to record breathing patterns are discussed.
Glomeruli are functional units in the olfactory system. The mouse olfactory bulb contains roughly 2,000 glomeruli, each receiving inputs from olfactory sensory neurons (OSNs) that express a specific odorant receptor gene. Odors typically activate many glomeruli in complex combinatorial patterns and it is unknown which features of neuronal activity in individual glomeruli contribute to odor perception. To address this, we used optogenetics to selectively activate single, genetically identified glomeruli in behaving mice. We found that mice could perceive the stimulation of a single glomerulus. Single-glomerulus stimulation was also detected on an intense odor background. In addition, different input intensities and the timing of input relative to sniffing were discriminated through one glomerulus. Our data suggest that each glomerulus can transmit odor information using identity, intensity and temporal coding cues. These multiple modes of information transmission may enable the olfactory system to efficiently identify and localize odor sources.
Many species are critically dependent on olfaction for survival. In the main olfactory system of mammals, odours are detected by sensory neurons that express a large repertoire of canonical odorant receptors and a much smaller repertoire of trace amine-associated receptors (TAARs). Odours are encoded in a combinatorial fashion across glomeruli in the main olfactory bulb, with each glomerulus corresponding to a specific receptor. The degree to which individual receptor genes contribute to odour perception is unclear. Here we show that genetic deletion of the olfactory Taar gene family, or even a single Taar gene (Taar4), eliminates the aversion that mice display to low concentrations of volatile amines and to the odour of predator urine. Our findings identify a role for the TAARs in olfaction, namely, in the high-sensitivity detection of innately aversive odours. In addition, our data reveal that aversive amines are represented in a non-redundant fashion, and that individual main olfactory receptor genes can contribute substantially to odour perception.
Illuminating vertebrate olfactory processing.The Journal of neuroscience : the official journal of the Society for Neuroscience 2012
H. Spors, D. Albeanu, V. N. Murthy, D. Rinberg, N. Uchida, M. Wachowiak, and R. W. Friedrich The Journal of neuroscience : the official journal of the Society for Neuroscience, 32:14102-8 (2012)
The olfactory system encodes information about molecules by spatiotemporal patterns of activity across distributed populations of neurons and extracts information from these patterns to control specific behaviors. Recent studies used in vivo recordings, optogenetics, and other methods to analyze the mechanisms by which odor information is encoded and processed in the olfactory system, the functional connectivity within and between olfactory brain areas, and the impact of spatiotemporal patterning of neuronal activity on higher-order neurons and behavioral outputs. The results give rise to a faceted picture of olfactory processing and provide insights into fundamental mechanisms underlying neuronal computations. This review focuses on some of this work presented in a Mini-Symposium at the Annual Meeting of the Society for Neuroscience in 2012.
Mitral/tufted cells of the olfactory bulb receive odorant information from receptor neurons and transmit this information to the cortex. Studies in awake behaving animals have found that sustained responses of mitral cells to odorants are rare, suggesting sparse combinatorial representation of the odorants. Careful alignment of mitral cell firing with the phase of the respiration cycle revealed brief transient activity in the larger population of mitral cells, which respond to odorants during a small fraction of the respiration cycle. Responses of these cells are therefore temporally sparse. Here, we propose a mathematical model for the olfactory bulb network that can reproduce both combinatorially and temporally sparse mitral cell codes. We argue that sparse codes emerge as a result of the balance between mitral cells' excitatory inputs and inhibition provided by the granule cells. Our model suggests functional significance for the dendrodendritic synapses mediating interactions between mitral and granule cells.
Olfactory systems encode odours by which neurons respond and by when they respond. In mammals, every sniff evokes a precise, odour-specific sequence of activity across olfactory neurons. Likewise, in a variety of neural systems, ranging from sensory periphery to cognitive centres, neuronal activity is timed relative to sampling behaviour and/or internally generated oscillations. As in these neural systems, relative timing of activity may represent information in the olfactory system. However, there is no evidence that mammalian olfactory systems read such cues. To test whether mice perceive the timing of olfactory activation relative to the sniff cycle ('sniff phase'), we used optogenetics in gene-targeted mice to generate spatially constant, temporally controllable olfactory input. Here we show that mice can behaviourally report the sniff phase of optogenetically driven activation of olfactory sensory neurons. Furthermore, mice can discriminate between light-evoked inputs that are shifted in the sniff cycle by as little as 10 milliseconds, which is similar to the temporal precision of olfactory bulb odour responses. Electrophysiological recordings in the olfactory bulb of awake mice show that individual cells encode the timing of photoactivation in relation to the sniff in both the timing and the amplitude of their responses. Our work provides evidence that the mammalian olfactory system can read temporal patterns, and suggests that timing of activity relative to sampling behaviour is a potent cue that may enable accurate olfactory percepts to form quickly.
We analyze the responses of human observers to an ensemble of monomolecular odorants. Each odorant is characterized by a set of 146 perceptual descriptors obtained from a database of odor character profiles. Each odorant is therefore represented by a point in a highly multidimensional sensory space. In this work we study the arrangement of odorants in this perceptual space. We argue that odorants densely sample a two-dimensional curved surface embedded in the multidimensional sensory space. This surface can account for more than half of the variance of the perceptual data. We also show that only 12% of experimental variance cannot be explained by curved surfaces of substantially small dimensionality (<10). We suggest that these curved manifolds represent the relevant spaces sampled by the human olfactory system, thereby providing surrogates for olfactory sensory space. For the case of 2D approximation, we relate the two parameters on the curved surface to the physico-chemical parameters of odorant molecules. We show that one of the dimensions is related to eigenvalues of molecules’ connectivity matrix, while the other is correlated with measures of molecules’ polarity. We discuss the behavioral significance of these findings.
In terrestrial vertebrates, sniffing controls odorant access to receptors, and therefore sets the timescale of olfactory stimuli. We found that odorants evoked precisely sniff-locked activity in mitral/tufted cells in the olfactory bulb of awake mouse. The trial-to-trial response jitter averaged 12 ms, a precision comparable to other sensory systems. Individual cells expressed odor-specific temporal patterns of activity and, across the population, onset times tiled the duration of the sniff cycle. Responses were more tightly time-locked to the sniff phase than to the time after inhalation onset. The spikes of single neurons carried sufficient information to discriminate odors. In addition, precise locking to sniff phase may facilitate ensemble coding by making synchrony relationships across neurons robust to variation in sniff rate. The temporal specificity of mitral/tufted cell output provides a potentially rich source of information for downstream olfactory areas.
We present a model for olfactory coding based on spatial representation of glomerular responses. In this model distinct odorants activate specific subsets of glomeruli, dependent on the odorant's chemical identity and concentration. The glomerular response specificities are understood statistically, based on experimentally measured distributions of activation thresholds. A simple version of the model, in which glomerular responses are binary (the all-or-nothing model), allows us to account quantitatively for the following results of human/rodent olfactory psychophysics: 1) just noticeable differences in the perceived concentration of a single odor (Weber ratios) are as low as dC/C approximately 0.04; 2) the number of simultaneously perceived odors can be as high as 12; and 3) extensive lesions of the olfactory bulb do not lead to significant changes in detection or discrimination thresholds. We conclude that a combinatorial code based on a binary glomerular response is sufficient to account for several important features of the discrimination capacity of the mammalian olfactory system.
Prior Publications (9)
More than 50 years have passed since the first recording of neuronal responses to an odor stimulus from the primary olfactory brain area, the main olfactory bulb. During this time very little progress has been achieved in understanding neuronal dynamics in the olfactory bulb in awake behaving animals, which is very different from that in anesthetized preparations. In this paper we formulate a new framework containing the main reasons for studying olfactory neuronal dynamics in awake animals and review advances in the field within this new framework.
Sparse odor coding in awake behaving mice.The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 2006
D. Rinberg, A. Koulakov, and A. Gelperin The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 26:8857-65 (2006)
Responses of mitral cells represent the results of the first stage of odor processing in the olfactory bulb. Most of our knowledge about mitral cell activity has been obtained from recordings in anesthetized animals. We compared odor-elicited changes in firing rate of mitral cells in awake behaving mice and in anesthetized mice. We show that odor-elicited changes in mitral cell firing rate were larger and more frequently observed in the anesthetized than in the awake condition. Only 27% of mitral cells that showed a response to odors in the anesthetized state were also odor responsive in the awake state. The amplitude of their response in the awake state was smaller, and some of the responses changed sign compared with their responses in the anesthetized state. The odor representation in the olfactory bulb is therefore sparser in awake behaving mice than in anesthetized preparations. A qualitative explanation of the mechanism responsible for this phenomenon is proposed.
The basic psychophysical principle of speed-accuracy tradeoff (SAT) has been used to understand key aspects of neuronal information processing in vision and audition, but the principle of SAT is still debated in olfaction. In this study we present the direct observation of SAT in olfaction. We developed a behavioral paradigm for mice in which both the duration of odorant sampling and the difficulty of the odor discrimination task were controlled by the experimenter. We observed that the accuracy of odor discrimination increases with the duration of imposed odorant sampling, and that the rate of this increase is slower for harder tasks. We also present a unifying picture of two previous, seemingly disparate experiments on timing of odorant sampling in odor discrimination tasks. The presence of SAT in olfaction provides strong evidence for temporal integration in olfaction and puts a constraint on models of olfactory processing.
Nervous systems often face the problem of classifying stimuli and making decisions based on these classifications. The neurons involved in these tasks can be characterized as sensory or motor, according to their correlation with sensory stimulus or motor response. In this study we define a third class of neurons responsible for making perceptual decisions. Our mathematical formalism enables the weighting of neuronal units according to their contribution to decision making, thus narrowing the field for more detailed studies of underlying mechanisms. We develop two definitions of a contribution to decision making. The first definition states that decision making activity can be found at the points of emergence for behavioral correlations in the system. The second definition involves the study of propagation of noise in the network. The latter definition is shown to be equivalent to the first one in the cases when they can be compared. Our results suggest a new approach to analyzing decision making networks.
This paper deals with the problem of extracting the activity of individual neurons from multi-electrode recordings. Important aspects of this work are: 1) the sorting is done in two stages - a statistical model of the spikes from different cells is built and only then are occurrences of these spikes in the data detected by scanning through the original data, 2) the spike sorting is done in the frequency domain, 3) strict statistical tests are applied to determine if and how a spike should be classiffed, 4) the statistical model for detecting overlaping spike events is proposed, 5) slow dynamics of spike shapes are tracked during long experiments. Results from the application of these techniques to data collected from the escape response system of the American cockroach, Periplaneta americana, are presented.
Wind spectra and the response of the cercal system in the cockroach.Journal of Comparative Physiology. A, Neuroethology, Sensory, Neural, and Behavioral Physiology 2003
D. Rinberg, and H. Davidowitz Journal of Comparative Physiology. A, Neuroethology, Sensory, Neural, and Behavioral Physiology, 189:867-76 (2003)
Experiments on the cercal wind-sensing system of the American cockroach, Periplaneta americana, showed that the firing rate of the interneurons coding wind information depends on the bandwidth of random noise wind stimuli. The firing rate was shown to increase with decreases in the stimulus bandwidth, and be independent of changes in the total power of the stimulus with constant spectral composition. A detailed analysis of ethologically relevant stimulus parameters is presented. A phenomenological model of these relationships and their relevance to wind-mediated cockroach behavior is proposed.
A novel system for the generation and measurement of a two dimensional wind stimulus is proposed and described. This system was used to investigate the wind sensation of the American cockroach. The new aspects of this system are (a) a pair of computer driven wind tunnels that are shown to produce non-turbulent flows and (b) a novel fiber optic wind detector that measures both amplitude and direction of the wind. Winds can be produced and measured in behaviorally relevant frequency and amplitude ranges without perturbing the airflow. The combination of both the wind generation system and wind detector makes the system very flexible and allows the generation of stimuli with any given spectrum. The two dimensional wind stimulus is shown to be very reproducible. The wind detector is independent of the wind generation system so it can be used for measuring natural winds as well. Experimental data obtained on the cockroach are presented.