Simulations of information processing, control, and plasticity effects in the olfactory bulb

The olfactory system processes complex and varied information in its detection, recognition, and memory of odors. The exact functions that the olfactory bulb plays in this processing is still largely unknown. Studies were performed to help reveal bulb functionality in the olfactory system while contributing to the set of computer methods available for the study of neural systems.One interesting property of bulbar neurons is an increase in primary cell firing thresholds with depth. Since increased odor concentrations generally result in higher frequency inputs to the bulb and thus higher summation levels of primary cell membrane potentials, this threshold gradation transforms the frequency-encoded concentration data into a spatial representation in the number of primary cells responding in a single olfactory bulb glomerular region.Since this transformation relies on temporal summation of post-synaptic potentials (PSPs) to reflect concentration levels, direct physiological modeling of the transformation was possible while providing the added efficiency to permit the simulation of large numbers of cells and synaptic interactions. A novel physiological modeling methodology was developed for these tests that extends the extant physiological models to include time-constant and driving-force interactive effects between post-synaptic inputs. This novel method is derived using linear superposition of inputs to a lumped-circuit cell representation, resulting in a difference-of-exponentials PSP function that is more realistic and flexible than the common empirically-chosen alpha function.Also, the effects that interneuronal dendritic spines have on bulbar inhibitions were tested using biophysical computer simulations of primary-to-granule dendrodendritic reciprocal interactions. The graded strength properties of these synapses showed that reciprocal inhibitions to primary mitral cells are facilitated by the spine structures without the need of a high gain gradation while reducing lateral inhibition to other mitral cells. Furthermore, increases in the neck axial resistance of the synapsed spine further strengthen the reciprocal response and reduce the lateral inhibition; such resistance changes could therefore result in dendrodendritic synaptic plasticities and olfactory memory operations

Reconstruction of neuronal activity and connectivity patterns in the zebrafish olfactory bulb

In the olfactory bulb (OB), odors evoke distributed patterns of activity across glomeruli that are reorganized by networks of interneurons (INs). This reorganization results in multiple computations including a decorrelation of activity patterns across the output neurons, the mitral cells (MCs). To understand the mechanistic basis of these computations it is essential to analyze the relationship between function and structure of the underlying circuit. I combined in vivo twophoton calcium imaging with dense circuit reconstruction from complete serial block-face electron microscopy (SBEM) stacks of the larval zebrafish OB (4.5 dpf) with a voxel size of 9x9x25nm. To address bottlenecks in the workflow of SBEM, I developed a novel embedding and staining procedure that effectively reduces surface charging in SBEM and enables to acquire SBEM stacks with at least a ten-fold increase in both, signal-to-noise as well as acquisition speed. I set up a high throughput neuron reconstruction pipeline with >30 professional tracers that is available for the scientific community (ariadne-service.com). To assure efficient and accurate circuit reconstruction, I developed PyKNOSSOS, a Python software for skeleton tracing and synapse annotation, and CORE, a skeleton consolidation procedure that combines redundant reconstruction with targeted expert input. Using these procedures I reconstructed all neurons (>1000) in the larval OB. Unlike in the adult OB, INs were rare and appeared to represent specific subtypes, indicating that different sub-circuits develop sequentially. MCs were uniglomerular whereas inter-glomerular projections of INs were complex and biased towards groups of glomeruli that receive input from common types of sensory neurons. Hence, the IN network in the OB exhibits a topological organization that is governed by glomerular identity. Calcium imaging revealed that the larval OB circuitry already decorrelates activity patterns evoked by similar odors. The comparison of inter-glomerular connectivity to the functional interactions between glomeruli indicates that pattern decorrelation depends on specific, non-random inter-glomerular IN projections. Hence, the topology of IN networks in the OB appears to be an important determinant of circuit function

Olfactory object recognition, segmentation, adaptation, target seeking, and discrimination by the network of the olfactory bulb and cortex: computational model and experimental data

Mammals are poor at individuating the separate components that comprise odor mixtures, but not when components enter environment serially and when there is top-down expectation. Li proposed in 1990 an odor segmentation mechanism using the centrifugal feedback from the olfactory cortex to the olfactory bulb. This feedback suppresses the bulbar responses to the ongoing and already recognized odors so that a subsequent addition of a foreground odor can be singled out for recognition. Additionally, the feedback can depend on context so as to, for example, enhance sensitivity to a target odor or improve discrimination between similar odors. I review experimental data that have since emerged in relation to the computational predictions and implications, and suggest experiments to test the model further

Odor coding and memory traces in the antennal lobe of honeybee

In dieser Arbeit werden zwei wesentliche neue Ergebnisse vorgestellt. Das erste bezieht sich auf die olfaktorische Kodierung und das zweite auf das sensorische Gedaechtnis. Beide Phaenomene werden am Beispiel des Gehirns der Honigbiene untersucht. In Bezug auf die olfaktorische Kodierung zeige ich, dass die neuronale Dynamik waehrend der Stimulation im Antennallobus duftspezifische Trajektorien beschreibt, die in duftspezifischen Attraktoren enden. Das Zeitinterval, in dem diese Attraktoren erreicht werden, betraegt unabhaengig von der Identitaet und der Konzentration des Duftes ungefaehr 800 ms. Darueber hinaus zeige ich, dass Support-Vektor Maschinen, und insbesondere Perzeptronen, ein realistisches und biologisches Model der Wechselwirkung zwischen dem Antennallobus (dem kodierenden Netwerk) und dem Pilzkoerper (dem dekodierenden Netzwerk) darstellen. Dieses Model kann sowohl Reaktionszeiten von ca. 300 ms als auch die Invarianz der Duftwahrnehmung gegenueber der Duftkonzentration erklaeren. In Bezug auf das sensorische Gedaechtnis zeige ich, dass eine einzige Stimulation ohne Belohnung dem Hebbschen Postulat folgend Veraenderungen der paarweisen Korrelationen zwischen Glomeruli induziert. Ich zeige, dass diese Veranderungen der Korrelationen bei 2/3 der Bienen ausreichen, um den letzten Stimulus zu bestimmen. In der zweiten Minute nach der Stimulation ist eine erfolgreiche Bestimmung des Stimulus nur bei 1/3 der Bienen moeglich. Eine Hauptkomponentenanalyse der spontanen Aktivitaet laesst erkennen, dass das dominante Muster des Netzwerks waehrend der spontanen Aktivitaet nach, aber nicht vor der Stimulation das duftinduzierte Aktivitaetsmuster bei 2/3 der Bienen nachbildet. Man kann deshalb die duftinduzierten (Veraenderungen der) Korrelationen als Spuren eines Kurzzeitgedaechtnisses bzw. als Hebbsche "Reverberationen" betrachtet werden.Two major novel results are reported in this work. The first concerns olfactory coding and the second concerns sensory memory. Both phenomena are investigated in the brain of the honeybee as a model system. Considering olfactory coding I demonstrate that the neural dynamics in the antennal lobe describe odor-specific trajectories during stimulation that converge to odor-specific attractors. The time interval to reach these attractors is, regardless of odor identity and concentration, approximately 800 ms. I show that support-vector machines and, in particular perceptrons provide a realistic and biological model of the interaction between the antennal lobe (coding network) and the mushroom body (decoding network). This model can also account for reaction-times of about 300 ms and for concentration invariance of odor perception. Regarding sensory memory I show that a single stimulation without reward induces changes of pairwise correlation between glomeruli in a Hebbian-like manner. I demonstrate that those changes of correlation suffice to retrieve the last stimulus presented in 2/3 of the bees studied. Succesful retrieval decays to 1/3 of the bees within the second minute after stimulation. In addition, a principal-component analysis of the spontaneous activity reveals that the dominant pattern of the network during the spontaneous activity after, but not before stimulation, reproduces the odor-induced activity pattern in 2/3 of the bees studied. One can therefore consider the odor-induced (changes of) correlation as traces of a short-term memory or as Hebbian reverberations

Is there a space–time continuum in olfaction?

The coding of olfactory stimuli across a wide range of organisms may rely on fundamentally similar mechanisms in which a complement of specific odorant receptors on olfactory sensory neurons respond differentially to airborne chemicals to initiate the process by which specific odors are perceived. The question that we address in this review is the role of specific neurons in mediating this sensory system—an identity code—relative to the role that temporally specific responses across many neurons play in producing an olfactory perception—a temporal code. While information coded in specific neurons may be converted into a temporal code, it is also possible that temporal codes exist in the absence of response specificity for any particular neuron or subset of neurons. We review the data supporting these ideas, and we discuss the research perspectives that could help to reveal the mechanisms by which odorants become perceptions

Data-driven modeling of the olfactory neural codes and their dynamics in the insect antennal lobe

Recordings from neurons in the insects' olfactory primary processing center, the antennal lobe (AL), reveal that the AL is able to process the input from chemical receptors into distinct neural activity patterns, called olfactory neural codes. These exciting results show the importance of neural codes and their relation to perception. The next challenge is to \emph{model the dynamics} of neural codes. In our study, we perform multichannel recordings from the projection neurons in the AL driven by different odorants. We then derive a neural network from the electrophysiological data. The network consists of lateral-inhibitory neurons and excitatory neurons, and is capable of producing unique olfactory neural codes for the tested odorants. Specifically, we (i) design a projection, an odor space, for the neural recording from the AL, which discriminates between distinct odorants trajectories (ii) characterize scent recognition, i.e., decision-making based on olfactory signals and (iii) infer the wiring of the neural circuit, the connectome of the AL. We show that the constructed model is consistent with biological observations, such as contrast enhancement and robustness to noise. The study answers a key biological question in identifying how lateral inhibitory neurons can be wired to excitatory neurons to permit robust activity patterns

Data driven approaches for investigating molecular heterogeneity of the brain

It has been proposed that one of the clearest organizing principles for most sensory systems is the existence of parallel subcircuits and processing streams that form orderly and systematic mappings from stimulus space to neurons. Although the spatial heterogeneity of the early olfactory circuitry has long been recognized, we know comparatively little about the circuits that propagate sensory signals downstream. Investigating the potential modularity of the bulb’s intrinsic circuits proves to be a difficult task as termination patterns of converging projections, as with the bulb’s inputs, are not feasibly realized. Thus, if such circuit motifs exist, their detection essentially relies on identifying differential gene expression, or “molecular signatures,” that may demarcate functional subregions. With the arrival of comprehensive (whole genome, cellular resolution) datasets in biology and neuroscience, it is now possible for us to carry out large-scale investigations and make particular use of the densely catalogued, whole genome expression maps of the Allen Brain Atlas to carry out systematic investigations of the molecular topography of the olfactory bulb’s intrinsic circuits. To address the challenges associated with high-throughput and high-dimensional datasets, a deep learning approach will form the backbone of our informatic pipeline. In the proposed work, we test the hypothesis that the bulb’s intrinsic circuits are parceled into distinct, parallel modules that can be defined by genome-wide patterns of expression. In pursuit of this aim, our deep learning framework will facilitate the group-registration of the mitral cell layers of ~ 50,000 in-situ olfactory bulb circuits to test this hypothesis

Rapid Odor Processing in the Honeybee Antennal Lobe Network

In their natural environment, many insects need to identify and evaluate behaviorally relevant odorants on a rich and dynamic olfactory background. Behavioral studies have demonstrated that bees recognize learned odors within <200 ms, indicating a rapid processing of olfactory input in the sensory pathway. We studied the role of the honeybee antennal lobe network in constructing a fast and reliable code of odor identity using in vivo intracellular recordings of individual projection neurons (PNs) and local interneurons (LNs). We found a complementary ensemble code where odor identity is encoded in the spatio-temporal pattern of response latencies as well as in the pattern of activated and inactivated PN firing. This coding scheme rapidly reaches a stable representation within 50–150 ms after stimulus onset. Testing an odor mixture versus its individual compounds revealed different representations in the two morphologically distinct types of lateral- and median PNs (l- and m-PNs). Individual m-PNs mixture responses were dominated by the most effective compound (elemental representation) whereas l-PNs showed suppressed responses to the mixture but not to its individual compounds (synthetic representation). The onset of inhibition in the membrane potential of l-PNs coincided with the responses of putative inhibitory interneurons that responded significantly faster than PNs. Taken together, our results suggest that processing within the LN network of the AL is an essential component of constructing the antennal lobe population code