Illuminating Vertebrate Olfactory Processing

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

Decorrelation of Odor Representations via Spike Timing-Dependent Plasticity

The non-topographical representation of odor quality space differentiates early olfactory representations from those in other sensory systems. Decorrelation among olfactory representations with respect to physical odorant similarities has been proposed to rely upon local feed-forward inhibitory circuits in the glomerular layer that decorrelate odor representations with respect to the intrinsically high-dimensional space of ligand–receptor potency relationships. A second stage of decorrelation is likely to be mediated by the circuitry of the olfactory bulb external plexiform layer. Computations in this layer, or in the analogous interneuronal network of the insect antennal lobe, are dependent on fast network oscillations that regulate the timing of mitral cell and projection neuron (MC/PN) action potentials; this suggests a largely spike timing-dependent metric for representing odor information, here proposed to be a precedence code. We first illustrate how the rate coding metric of the glomerular layer can be transformed into a spike precedence code in MC/PNs. We then show how this mechanism of representation, combined with spike timing-dependent plasticity at MC/PN output synapses, can progressively decorrelate high-dimensional, non-topographical odor representations in third-layer olfactory neurons. Reducing MC/PN oscillations abolishes the spike precedence code and blocks this progressive decorrelation, demonstrating the learning network's selectivity for these sparsely synchronized MC/PN spikes even in the presence of temporally disorganized background activity. Finally, we apply this model to odor representations derived from calcium imaging in the honeybee antennal lobe, and show how odor learning progressively decorrelates odor representations, and how the abolition of PN oscillations impairs odor discrimination

Neural codes formed by small and temporally precise populations in auditory cortex

The encoding of sensory information by populations of cortical neurons forms the basis for perception but remains poorly understood. To understand the constraints of cortical population coding we analyzed neural responses to natural sounds recorded in auditory cortex of primates (Macaca mulatta). We estimated stimulus information while varying the composition and size of the considered population. Consistent with previous reports we found that when choosing subpopulations randomly from the recorded ensemble, the average population information increases steadily with population size. This scaling was explained by a model assuming that each neuron carried equal amounts of information, and that any overlap between the information carried by each neuron arises purely from random sampling within the stimulus space. However, when studying subpopulations selected to optimize information for each given population size, the scaling of information was strikingly different: a small fraction of temporally precise cells carried the vast majority of information. This scaling could be explained by an extended model, assuming that the amount of information carried by individual neurons was highly nonuniform, with few neurons carrying large amounts of information. Importantly, these optimal populations can be determined by a single biophysical marker—the neuron's encoding time scale—allowing their detection and readout within biologically realistic circuits. These results show that extrapolations of population information based on random ensembles may overestimate the population size required for stimulus encoding, and that sensory cortical circuits may process information using small but highly informative ensembles

Illuminating Vertebrate Olfactory Processing

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.Molecular and Cellular Biolog

Connectivity, plasticity, and function of neuronal circuits in the zebrafish olfactory forebrain

For most living animals such as worms, insects, fishes, rodents and humans, chemical cues from the environment (odorants) play critical roles in guiding behaviors important for survival, including preying, mating, breeding, and escaping. How those odorants are detected, identified, learned, remembered, and used by the nervous system is a longstanding interest for neuroscientists. An animal that is well-suited to study the processing of odor information at the level of neuronal circuits is the zebrafish (Danio rerio) because its small brain size allows for exhaustive quantitative measurements of neuronal activity patterns. In vertebrates, odorants are detected by olfactory sensory neurons in the nose and transmitted to the first olfactory processing center in the brain, the olfactory bulb (OB), as patterns of neuronal activities. In the OB, neuronal activity patterns from the nose are transformed into odor-specific spatiotemporal activity patterns across second order neurons, the mitral cells. These discrete neuronal activity patterns are broadcast to various target areas. The largest of these higher brain areas is piriform cortex or its teleost homolog, the posterior zone of dorsal telencephalon (Dp). In this higher brain region, an odor-encoding neuronal activity pattern from the OB is thought to be encoded as a "gestalt", or "odor object", and possibly stored in memory by specific modifications of functional connections between distributed neuronal ensembles. Such neuronal ensembles are also thought to be connected with other brain regions that involved in the control of different behaviors. Therefore, by inducing a specific activity pattern in the OB, which then retrieves related neuronal ensemble activities in a higher brain region, an odor cue (or even partial cue) recalls an odor object memory that may further trigger a specific set of behavioral responses in the animal. The mechanisms by which odor object memory is synthesized, stored, and recalled is of major interest in neuroscience because it may provide fundamental insights into associative memory functions. However, dissecting higher brain functions such as associative memory will first require basic understanding of connectivity, plasticity, and related modulating factors for the underlying neuronal circuits. In this inaugural dissertation, I present an approach to study the connectivity, plasticity, and cholinergic modulation of the neural circuits in Dp and present new insights into the synaptic organizations of this neuronal network. In results part one, I show that transgenes can be introduced directly into the adult zebrafish brain by herpes simplex type I viruses (HSV-1) or electroporation. I developed a new procedure to target electroporation to defined brain areas, e.g. Dp, and identified promoters that produced strong long-term expression. These new methods fill an important gap in the spectrum of molecular tools for zebrafish and are likely to have a wide range of applications. In results part two, I used a combination of electroporation, optogenetics, electrophysiology, and pharmacology to study the intrinsic connectivity and plasticity in neural circuits of Dp. I found that connectivity between any pair of excitatory neurons in Dp is extremely sparse (connection probability < 1.5 %). The connection probability of inhibitory synapses is also sparse but slightly higher (< 2.5 %). Furthermore, I found that connectivity can be functionally modified by activity-dependent synaptic plasticity including spike timing-dependent long-term potentiation. Moreover, I show that cholinergic agonists differentially modulate excitatory and inhibitory synaptic transmissions in Dp, consistent with the notion that cholinergic neuromodulation controls experience-dependent changes in functional connectivity. These findings show that the synaptic organization of Dp is similar to mammalian piriform cortex and provide quantitative insights into the functional organization of a brain area that is likely to be involved in associative memory

Olfactory cortical neurons read out a relative time code in the olfactory bulb

Odor stimulation evokes complex spatiotemporal activity in the olfactory bulb, suggesting that the identity of activated neurons as well as the timing of their activity convey information about odors. However, whether and how downstream neurons decipher these temporal patterns remains debated. We addressed this question by measuring the spiking activity of downstream neurons while optogenetically stimulating two foci in the olfactory bulb with varying relative timing in mice. We found that the overall spike rates of piriform cortex neurons were sensitive to the relative timing of activation. Posterior piriform cortex neurons showed higher sensitivity to relative input times than neurons in the anterior piriform cortex. In contrast, olfactory bulb neurons rarely showed such sensitivity. Thus, the brain can transform a relative time code in the periphery into a firing-rate-based representation in central brain areas, providing evidence for the relevance of relative time-based code in the olfactory bulb

Odour Processing By Principal Neurons of the Piriform Cortex In Vivo

The piriform cortex (PC) is important for the cortical processing of olfactory information. The PC is widely viewed as a pattern recognition device whose primary function is the formation of ‘odour objects’, that is, the perception of complex odours comprising many chemical components as single olfactory percepts (e.g. the scent of a rose), a task that is heavily dependent on the intracortical associational network. Two types of glutamatergic principal neurons are present in approximately equal numbers in layer 2 of the PC: semilunar (SL) and superficial pyramidal (SP) cells. Despite a long-standing misconception that the principal neurons of the PC are a functionally homogenous population, recent work has shown that SL and SP cells differ significantly in their connectivity and in vitro electrophysiology. Specifically, emerging data has indicated that intracortical connectivity increases with increasingly deep somatic locations, suggesting that, in response to olfactory stimulation, cortical computations shift from afferent (sensory) processing to associative processing down the PC superficial-to-deep axis. In light of the important differences between the two main classes of principal neurons, we hypothesised that SL and SP cells contribute differentially to the cortical processing of olfactory sensory information. In this thesis, we examined the odour responses of layer 2 principal neurons in the anterior PC using whole-cell patch clamp electrophysiology. We show that odour responses are highly variable and richly nuanced in vivo; however, they can be broadly separated into three basic categories: excitation, inhibition and unresponsiveness. Our current clamp data revealed that an intrinsic property, the spike after-hyperpolarisation (AHP), correlates strongly with the somatic laminar depth, suggesting that the AHP could be used to identify neurons (SL or SP cells) recorded in vivo. Importantly, current clamp data indicate that olfactory excitatory tuning correlates strongly with the AHP in vivo, such that putative SP cells (characterised by a small AHP) are more broadly excited by odours than putative SL cells (characterised by a large AHP), presumably due to a difference in intracortical connectivity. These results further suggest that, rather than assuming a sharp dichotomy of neuronal phenotypes, SL-like cells gradually transition into SP-like cells along the cortical superficial-to-deep axis. Voltage clamp data indicate that principal neurons are under a substantial level of tonic inhibition in the absence of odour. We show that spontaneous and odour-evoked inhibition dominates and scales with excitation under physiological conditions. These results suggest that local inhibition contributes to the reported sparse odour coding in the cortex. Overall, these data are consistent with our proposed model of the anterior PC excitatory network, which posits that 1) principal neuron phenotype transitions smoothly across the cortical superficial-to-deep axis and 2) principal neurons become increasingly incorporated into the local intracortical microcircuits with increasingly deep somatic location, as a result, 3) neuronal excitatory tuning becomes progressively broader with increasing somatic depth. These results suggest that SL cells may be important for decorrelating overlapping input patterns and hence preserving the salient olfactory attributes of an odour, whereas SP cells are more heavily implicated in the associative aspect of olfactory processing