Shree Hari Gautam

Maximizing Sensory Dynamic Range by Tuning the Cortical State to Criticality.

Modulation of interactions among neurons can manifest as dramatic changes in the state of population dynamics in cerebral cortex. How such transitions in cortical state impact the information processing performed by cortical circuits is not clear. Here we performed experiments and computational modeling to determine how somatosensory dynamic range depends on cortical state. We used microelectrode arrays to record ongoing and whisker stimulus-evoked population spiking activity in somatosensory cortex of urethane anesthetized rats. We observed a continuum of different cortical states; at one extreme population activity exhibited small scale variability and was weakly correlated, the other extreme had large scale fluctuations and strong correlations. In experiments, shifts along the continuum often occurred naturally, without direct manipulation. In addition, in both the experiment and the model we directly tuned the cortical state by manipulating inhibitory synaptic interactions. Our principal finding was that somatosensory dynamic range was maximized in a specific cortical state, called criticality, near the tipping point midway between the ends of the continuum. The optimal cortical state was uniquely characterized by scale-free ongoing population dynamics and moderate correlations, in line with theoretical predictions about criticality. However, to reproduce our experimental findings, we found that existing theory required modifications which account for activity-dependent depression. In conclusion, our experiments indicate that in vivo sensory dynamic range is maximized near criticality and our model revealed an unanticipated role for activity-dependent depression in this basic principle of cortical function.

Retronasal Odor Representations in the Dorsal Olfactory Bulb of Rats

Animals perceive their olfactory environment not only from odors originating in the external world (orthonasal route) but also from odors released in the oral cavity while eating food (retronasal route). Retronasal olfaction is crucial for the perception of food flavor in humans. However, little is known about the retronasal stimulus coding in the brain. The most basic questions are if and how route affects the odor representations at the level of the olfactory bulb (OB), where odor quality codes originate. We used optical calcium imaging of presynaptic dorsal OB responses to odorants in anesthetized rats to ask whether the rat OB could be activated retronasally, and how these responses compare to orthonasal responses under similar conditions. We further investigated the effects of specific odorant properties on orthonasal versus retronasal response patterns. We found that at a physiologically relevant flow rate, retronasal odorants can effectively reach the olfactory receptor neurons, eliciting glomerular response patterns that grossly overlap with those of orthonasal responses, but differ from the orthonasal patterns in the response amplitude and temporal dynamics. Interestingly, such differences correlated well with specific odorant properties. Less volatile odorants yielded relatively smaller responses retronasally, but volatility did not affect relative temporal profiles. More polar odorants responded with relatively longer onset latency and time to peak retronasally, but polarity did not affect relative response magnitudes. These data provide insight into the early stages of retronasal stimulus coding and establish relationships between orthonasal and retronasal odor representations in the rat OB.

Head-mountable high speed camera for optical neural recording

We report a head-mountable CMOS camera for recording rapid neuronal activity in freely moving rodents using fluorescent activity reporters. This small, lightweight camera is capable of detecting small changes in light intensity (0.2% ΔI/I) at 500fps. The camera has a resolution of 32×32, sensitivity of 0.62V/lxs, conversion gain of 0.52μV/e(-) and well capacity of 2.1Me(-). The camera, containing intensity offset subtraction circuitry within the imaging chip, is part of a miniaturized epi-fluorescent microscope and represents a first generation, mobile scientific-grade, physiology imaging camera.

Evidence that the sweetness of odors depends on experience in rats.

Humans describe their perception of certain odorants in terms of taste qualities (e.g., sweet). It has also been found that in humans, novel odorants can rapidly and irreversibly acquire a taste, even after just a single pairing with a taste. It remains unclear whether flavor objects in general, and odor-taste generalizations in particular, are experience-dependent. Interactions might result from a failure by humans to sufficiently analyze the olfactory and gustatory components of compound flavorants. Here, we tested odor-taste generalizations in rats with or without paired exposure to an odorant and a tastant. We evaluated the generalization of conditioned odor aversion to tastants by rats. Our findings suggest that rats behave toward putatively tasteless retronasal odorants as if they were sweet only after prior paired experience of the odorant with a sweet tastant. These data support the hypothesis that taste-like qualities of odors are learned and are not innate. Furthermore, the present results suggest that acquisition of a taste quality by an odor need not depend on higher cognitive abilities. This study helps to establish the rat as a model for the study of behavioral neuroscience of flavor.

Direct Behavioral Evidence for Retronasal Olfaction in Rats

The neuroscience of flavor perception is becoming increasingly important to understand abnormal feeding behaviors and associated chronic diseases such as obesity. Yet, flavor research has mainly depended on human subjects due to the lack of an animal model. A crucial step towards establishing an animal model of flavor research is to determine whether the animal uses the retronasal mode of olfaction, an essential element of flavor perception. We designed a go- no go behavioral task to test the rats ability to detect and discriminate retronasal odorants. In this paradigm, tasteless aqueous solutions of odorants were licked by water-restricted head-fixed rats from a lick spout. Orthonasal contamination was avoided by employing a combination of a vacuum around the lick-spout and blowing clean air toward the nose. Flow models support the effectiveness of both approaches. The licked odorants were successfully discriminated by rats. Moreover, the tasteless odorant amyl acetate was reliably discriminated against pure distilled water in a concentration-dependent manner. The results from this retronasal odor discrimination task suggest that rats are capable of smelling retronasally. This direct behavioral evidence establishes the rat as a useful animal model for flavor research.

Voltage sensitive dye imaging system for awake and freely moving animals

A 32 times 32 pixel image sensor in bulk CMOS process for use in a custom voltage sensitive dye imaging system is presented. The system is to be mounted on awake and freely moving animals in order to measure brain activity. The image sensor is capable of on-chip temporal-differencing using a storage capacitor on-chip. Temporal-differencing is used to reduce the stress on the overall readout circuitry in order to meet size and power constraints of such a system. Each 75 mum times 75 mum pixel consists of a photodiode of 74 mum times 34 mum and a storage capacitor of 788 fF. The image sensor has a signal-to-noise ratio of 76 dB.

Retronasal odor concentration coding in glomeruli of the rat olfactory bulb

The mammalian olfactory system processes odorants presented orthonasally (inhalation through the nose) and also retronasally (exhalation), enabling identification of both external as well as internal objects during food consumption. There are distinct differences between ortho- and retronasal air flow patterns, psychophysics, multimodal integration, and glomerular responses. Recent work indicates that rats can also detect odors retronasally, that rats can associate retronasal odors with tastes, and that their olfactory bulbs (OBs) can respond to retronasal odorants but differently than to orthonasal odors. To further characterize retronasal OB input activity patterns, experiments here focus on determining the effects of odor concentration on glomerular activity by monitoring calcium activity in the dorsal OB of rats using a dextran-conjugated calcium-sensitive dye in vivo. Results showed reliable concentration-response curves that differed between odorants, and recruitment of additional glomeruli, as odor concentration increased. We found evidence of different concentration-response functions between glomeruli, that in turn depended on odor. Further, the relation between dynamics and concentration differed remarkably among retronasal odorants. These dynamics are suggested to reduce the odor map ambiguity based on response amplitude. Elucidating the coding of retronasal odor intensity is fundamental to the understanding of feeding behavior and the neural basis of flavor. These data further establish and refine the rodent model of flavor neuroscience.

Taste Quality and Intensity of 100 Stimuli as Reported by Rats: The Taste–Location Association Task

The interpretation of neural activity related to sensory stimulation requires an understanding of the subject’s perception of the stimulation. Previous methods used to evaluate the perception of chemosensory stimuli by rodents have distinct limitations. We developed a novel behavioral paradigm, the taste–location association task, to complement these methods. First we tested if rats are able to learn associations between five basic taste stimuli and their spatial locations. This spatial task was based on four prototypical tastants and water. All four rats trained to perform the task reached levels of performance well above chance. Control trials demonstrated that the rats used only taste cues. Further, the learned stimulus set was resistant to interference, allowing for generalization experiments performed subsequently. We tested the rats’ gustatory generalizations of 100 tastants to the five trained stimuli, both regarding their taste qualities as well as intensity ratings. The taste profiles generated by these experiments contribute to the understanding of how perception of the specific taste stimuli relate to the perception of the five basic taste qualities in intact behaving rats. In this large taste space we found that intensity plays a major role. Furthermore, umami stimuli were not reported as being similar to other basic tastants. Our new paradigm enables neurophysiological studies of taste-based learning and memory in awake, freely moving animals.

Millisecond, micron precision multi-whisker detector.

The neural mechanisms of somatosensory information processing in the rodent vibrissae system are a topic of intense debate and research. Certain hypotheses emphasize the importance of stick-slip whisker motion, high-frequency resonant vibrations, and/or the ability to decode complex textures. Other hypotheses focus on the importance of integrating information from multiple whiskers. Tests of the former require measurements of whisker motion that achieve high spatiotemporal accuracy without altering the mechanical properties of whiskers. Tests of the latter require the ability to monitor the motion of multiple whiskers simultaneously. Here we present a device that achieves both these requirements for two-dimensional whisker motion in the plane perpendicular to the whiskers. Moreover, the system we present is significantly less expensive (<

A theoretical framework for analyzing coupled neuronal networks: Application to the olfactory system

2.5 k) and simpler to build than alternative devices which achieve similar detection capabilities. Our system is based on two laser diodes and two linear cameras. It attains millisecond temporal precision and micron spatial resolution. We developed automated algorithms for processing the data collected by our device and benchmarked their performance against manual detection by human visual inspection. By this measure, our detection was successful with less than 10 µm deviation between the automated and manual detection, on average. Here, we demonstrate its utility in anesthetized rats by measuring the motion of multiple whiskers in response to an air puff.