A model of fasciculation and sorting in mixed populations of axons

We extend a recently proposed model (Chaudhuri et al., EPL 87, 20003 (2009)) aiming to describe the formation of fascicles of axons during neural development. The growing axons are represented as paths of interacting directed random walkers in two spatial dimensions. To mimic turnover of axons, whole paths are removed and new walkers are injected with specified rates. In the simplest version of the model, we use strongly adhesive short-range inter-axon interactions that are identical for all pairs of axons. We generalize the model to adhesive interactions of finite strengths and to multiple types of axons with type-specific interactions. The dynamic steady state is characterized by the position-dependent distribution of fascicle sizes. With distance in the direction of axon growth, the mean fascicle size and emergent time scales grow monotonically, while the degree of sorting of fascicles by axon type has a maximum at a finite distance. To understand the emergence of slow time scales, we develop an analytical framework to analyze the interaction between neighboring fascicles.Comment: 19 pages, 13 figures; version accepted for publication in Phys Rev

Computational physics of the mind

In the XIX century and earlier such physicists as Newton, Mayer, Hooke, Helmholtz and Mach were actively engaged in the research on psychophysics, trying to relate psychological sensations to intensities of physical stimuli. Computational physics allows to simulate complex neural processes giving a chance to answer not only the original psychophysical questions but also to create models of mind. In this paper several approaches relevant to modeling of mind are outlined. Since direct modeling of the brain functions is rather limited due to the complexity of such models a number of approximations is introduced. The path from the brain, or computational neurosciences, to the mind, or cognitive sciences, is sketched, with emphasis on higher cognitive functions such as memory and consciousness. No fundamental problems in understanding of the mind seem to arise. From computational point of view realistic models require massively parallel architectures

Enhancer Interaction Networks as a Means for Singular Olfactory Receptor Expression

SummaryThe transcriptional activation of one out of ∼2800 olfactory receptor (OR) alleles is a poorly understood process. Here, we identify a plethora of putative OR enhancers and study their in vivo activity in olfactory neurons. Distinguished by an unusual epigenetic signature, candidate OR enhancers are characterized by extensive interchromosomal interactions associated with OR transcription and share a similar pattern of transcription factor footprints. In particular, we establish the role of the transcription factor Bptf as a facilitator of both enhancer interactions and OR transcription. Our observations agree with the model whereby OR transcription occurs in the context of multiple interacting enhancers. Disruption of these interchromosomal interactions results in weak and multigenic OR expression, suggesting that the rare coincidence of numerous enhancers over a stochastically chosen OR may account for the singularity and robustness in OR transcription

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

Cloning and characterization of putative vomeronasal receptor genes in mouse

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Biology, 1996.Vita.Includes bibliographical references (leaves ).by Asher Davison.M.S

Phase lagging model of brain response to external stimuli - modeling of single action potential

In this paper we detail a phase lagging model of brain response to external stimuli. The model is derived using the basic laws of physics like conservation of energy law. This model eliminates the paradox of instantaneous propagation of the action potential in the brain. The solution of this model is then presented. The model is further applied in the case of a single neuron and is verified by simulating a single action potential. The results of this modeling are useful not only for the fundamental understanding of single action potential generation, but also they can be applied in case of neuronal interactions where the results can be verified against the real EEG signal.Comment: 19 page

External stimulation induces switches between neural oscillations: an illustrative feedback model

International audienc

The Murine Accessory Olfactory Bulb as a Model Chemosensory System: Experimental and Computational Analysis of Chemosensory Representations

A common challenge across sensory processing modalities is forming meaningful associations between the neural responses and the outside world. These neural representations of the world must then be integrated across different sensory systems contributing to each individuals perceptual experience. While there has been considerable study of sensory representations in the visual system of humans and multiple model organisms, other sensory domains, including olfaction, are less well understood. In this thesis, I set out to better understand the sensory representations of the mouse accessory olfactory system (AOS), a part of the olfactory system. The mouse AOS, our model chemosensory system, comprises peripheral vomeronasal sensory neurons (VSNs), the accessory olfactory bulb (AOB), and downstream effectors. Our work describes the neural representations of multiple sensory inputs in the AOS, specifically the representations of odorants in high dimensional chemical sensory space in the AOB, and how these representations are shaped by interactions within the circuit. Given the complex nature of olfactory chemosensory representations, the features of our model system may give new perspectives on the neural representation of the outside world. In a neural representation of olfactory information, both the interactions between each receptor and odor compounds as well as the circuit mediated interactions could potentially affect the neural representations of the outside world. The initial neural response comprises component interactions between each receptor and the odor; chemical signals must interact with physical receptors. However, chemosensory processing, such as olfaction, requires interpreting a large variety of potentially overlapping chemical cues from the environment with only a finite number of receptor types. This means that each chemical cue does not necessarily activate only one receptor type or region of the circuit, but rather the cue is likely to be represented by multiple receptor and odor component interactions. Also, the component parts of odors may be processed differently when presented in isolation versus in a more complex mixture, thus allowing the response to a particular odor to vary with chemical context. Moreover, once these component representations exist, interactions within the neural circuit may further shape these responses. For example, one might expect component parts of a complex odor to specifically inhibit other component parts. In the case of the accessory olfactory system this inhibition could be at the receptor level or at the level of the sensory representation in the accessory olfactory bulb (AOB). In Chapter 3, I describe the overall organization of chemosensory representations in the accessory olfactory bulb (AOB), which is found to be a modular map in which the primary associations of functional sensory responses are spatially organized relative to one another. I find these primary associations are condensations of the first order sensory neuron axon terminals, which form population response pooling structures called glomeruli. In these glomeruli, similar response types from those sensory neurons expressing one of the approximately 300 receptor types in the vomeronasal organ (VNO) co-converge. One purpose of converging inputs of neurons expressing the same receptor is likely to minimize noise, and I demonstrate that pooling of like receptor responses into glomeruli does increase neural signal relative to noise. However, I also observed a modular organization among and between glomeruli in which certain types or patterns of chemosensory responses are always spatially adjacent to one another, while others are much farther apart than would be expected by chance. I found this spatial modularity for both ethological stimuli (urine collected from conspecifics with widely divergent physiological endocrine status) and individual sulfated steroids. In Chapter 4, I explore the consequences of changing sensory context, specifically the presentation of multiple compounds, and the role that inhibition plays in the neural representation of the sensory stimuli. First, I tested whether the circuit responds differently to demands to represent a single odor than to demands to represent multiple odors by using odors that activate glomeruli both inside and outside of modules. I found that responses to mixtures rapidly diverge from the responses of individual component parts. Moreover, there was an effect of inhibition in modulating the response to preferred stimuli in all glomeruli. However, initial analysis of one type of pregnanolone responsive glomeruli demonstrated that the divergent response to mixtures in this type of glomerulus was not mediated by inhibition at the glomerular level, but was rather attributable to bottom-up effects from the interactions of multiple ligands with chemosensory receptors in the VNO. Nonetheless, I also demonstrated that in the AOB, the axon terminals of the same sensory neurons (glomeruli) are organized into modules that allow for feedback inhibition. Significant ionotropic glutamate receptor signal modulation was observed within modules, demonstrating that there are inhibition mediated effects in the representation of complex mixtures when glomeruli are co-locally arranged. Specifically, at both the level of the VSNs and also in AOB glomeruli, the response to allopregnanolone sulfate is inhibited by co-presentation with estradiol sulfate. This both significantly increases the relative representation of estradiol sulfate and shifts representation of allopregnanolone primarily within modules. These types of context dependent interactions depend on the spatial organization described in Chapter 3 as well as mixture context, and have the potential to optimize the representation of some chemical cues in a context specific manner

A Neuronal Identity Code for the Odorant Receptor-Specific and Activity-Dependent Axon Sorting

SummaryIn the mouse, olfactory sensory neurons (OSNs) expressing the same odorant receptor (OR) converge their axons to a specific set of glomeruli in the olfactory bulb. To study how OR-instructed axonal fasciculation is controlled, we searched for genes whose expression profiles are correlated with the expressed ORs. Using the transgenic mouse in which the majority of OSNs express a particular OR, we identified such genes coding for the homophilic adhesive molecules Kirrel2/Kirrel3 and repulsive molecules ephrin-A5/EphA5. In the CNGA2 knockout mouse, where the odor-evoked cation influx is disrupted, Kirrel2 and EphA5 were downregulated, while Kirrel3 and ephrin-A5 were upregulated, indicating that these genes are transcribed in an activity-dependent manner. Mosaic analysis demonstrated that gain of function of these genes generates duplicated glomeruli. We propose that a specific set of adhesive/repulsive molecules, whose expression levels are determined by OR molecules, regulate the axonal fasciculation of OSNs during the process of glomerular map formation