Modular construction of nervous systems: a basic principle of design for invertebrates and vertebrates

As evidenced by the proliferation of papers in the last 30 years it is now well accepted that an iterative columnar or modular organization of the neocortex is characteristic of mammalian sensory, motor and frontal association areas. This does not imply that all mammalian neocortical areas are thus arranged; exceptions occur, particularly in the rodents

The retinal ganglion cell axon's journey: Insights into molecular mechanisms of axon guidance

AbstractThe developing visual system has proven to be one of the most informative models for studying axon guidance decisions. The pathway is composed of the axons of a single neuronal cell type, the retinal ganglion cell (RGC), that navigate through a series of intermediate targets on route to their final destination. The molecular basis of optic pathway development is beginning to be elucidated with cues such as netrins, Slits and ephrins playing a key role. Other factors best characterised for their role as morphogens in patterning developing tissues, such as sonic hedgehog (Shh) and Wnts, also act directly on RGC axons to influence guidance decisions. The transcriptional basis of the spatial–temporal expression of guidance cues and their cognate receptors within the developing optic pathway as well as mechanisms underlying the plasticity of guidance responses also are starting to be understood. This review will focus on our current understanding of the molecular mechanisms directing the early development of functional connections in the developing visual system and the insights these studies have provided into general mechanisms of axon guidance

A Single-Cell Level and Connectome-Derived Computational Model of the Drosophila Brain

Computer simulations play an important role in testing hypotheses, integrating knowledge, and providing predictions of neural circuit functions. While considerable effort has been dedicated into simulating primate or rodent brains, the fruit fly (Drosophila melanogaster) is becoming a promising model animal in computational neuroscience for its small brain size, complex cognitive behavior, and abundancy of data available from genes to circuits. Moreover, several Drosophila connectome projects have generated a large number of neuronal images that account for a significant portion of the brain, making a systematic investigation of the whole brain circuit possible. Supported by FlyCircuit (http://www.flycircuit.tw), one of the largest Drosophila neuron image databases, we began a long-term project with the goal to construct a whole-brain spiking network model of the Drosophila brain. In this paper, we report the outcome of the first phase of the project. We developed the Flysim platform, which (1) identifies the polarity of each neuron arbor, (2) predicts connections between neurons, (3) translates morphology data from the database into physiology parameters for computational modeling, (4) reconstructs a brain-wide network model, which consists of 20,089 neurons and 1,044,020 synapses, and (5) performs computer simulations of the resting state. We compared the reconstructed brain network with a randomized brain network by shuffling the connections of each neuron. We found that the reconstructed brain can be easily stabilized by implementing synaptic short-term depression, while the randomized one exhibited seizure-like firing activity under the same treatment. Furthermore, the reconstructed Drosophila brain was structurally and dynamically more diverse than the randomized one and exhibited both Poisson-like and patterned firing activities. Despite being at its early stage of development, this single-cell level brain model allows us to study some of the fundamental properties of neural networks including network balance, critical behavior, long-term stability, and plasticity

Identifying the neural basis of female receptivity within and between Drosophila species

The neural mechanisms that underlie a female’s willingness to mate remain largely unknown. To identify the neural basis of female receptivity, I used a combination of genetic tools to temporarily induce hyperactivation or suppression of particular neural regions and receptors, then scored their effect on Drosophila melanogaster female receptivity towards conspecific or heterospecific males. I found that silencing the antennal lobe reduced female receptivity, while silencing the mushroom bodies increased receptivity towards conspecific males. Hyperactivation of Odorant receptor 47b or the mushroom body increased female receptivity. In contrast, silencing or hyperactivation of target regions had no effect on female receptivity between species. Identifying the neural basis of female receptivity within a species can illuminate how neuronal circuits integrate multiple sources of information from various modalities to subsequently produce behaviour. Further, identifying the regions that allow for between-species discrimination can also contribute to our understanding of the neural origin of speciation

The role of Ten-m3 in the development of the mouse thalamostriatal pathway

Thalamostriatal afferents originating from the parafascicular nucleus (PF) target the striatal matrix in a topographically organised and patchy distribution. The molecular mechanisms underlying the development of this pathway are unknown. We have identified Ten-m3, a transmembrane glycoprotein, as the first molecular candidate in the formation of this circuit. Ten-m3 is expressed in the striatal matrix and PF in topographically corresponding high-dorsal to low-ventral gradients. In the striatum, this is overlaid on a patchy expression pattern. In Ten-m3 knock-out mice, thalamic terminals remain confined to the matrix but show altered topography, and the patchy patterning of terminals is lost. Evidence suggests that changes may be region specific. These anatomical changes correlate with delayed motor-skill learning in Ten-m3 knock-outs. During development, temporal expression of Ten-m3 correlates with the first ingrowth of thalamostriatal branches, and Ten-m3-positive patches overlap with dense clusters of thalamic terminals. Complex differences are observed throughout development in Ten-m3 knock-outs. In addition to direct homophilic mechanisms, we propose that Ten-m3 may act indirectly by altering levels of Epha7. Together, these data suggest that Ten-m3 acts via multiple mechanisms to organise topography and instruct complex organisation of thalamic terminals within the striatal matrix for the development of normal motor learning strategies

The role of Ten-m3 in the development of the mouse thalamostriatal pathway

Thalamostriatal afferents originating from the parafascicular nucleus (PF) target the striatal matrix in a topographically organised and patchy distribution. The molecular mechanisms underlying the development of this pathway are unknown. We have identified Ten-m3, a transmembrane glycoprotein, as the first molecular candidate in the formation of this circuit. Ten-m3 is expressed in the striatal matrix and PF in topographically corresponding high-dorsal to low-ventral gradients. In the striatum, this is overlaid on a patchy expression pattern. In Ten-m3 knock-out mice, thalamic terminals remain confined to the matrix but show altered topography, and the patchy patterning of terminals is lost. Evidence suggests that changes may be region specific. These anatomical changes correlate with delayed motor-skill learning in Ten-m3 knock-outs. During development, temporal expression of Ten-m3 correlates with the first ingrowth of thalamostriatal branches, and Ten-m3-positive patches overlap with dense clusters of thalamic terminals. Complex differences are observed throughout development in Ten-m3 knock-outs. In addition to direct homophilic mechanisms, we propose that Ten-m3 may act indirectly by altering levels of Epha7. Together, these data suggest that Ten-m3 acts via multiple mechanisms to organise topography and instruct complex organisation of thalamic terminals within the striatal matrix for the development of normal motor learning strategies

Micro-, Meso- and Macro-Connectomics of the Brain

Neurosciences, Neurolog

A Tale of Two Direction Codes in Rat Retrosplenial Cortex: Uncovering the Neural Basis of Spatial Orientation in Complex Space

Head direction (HD) cells only become active whenever a rat faces one direction and stay inactive when it faces others, producing a unimodal activity distribution. Working together in a network, HD cells are considered the neural basis supporting a sense of direction. The retrosplenial cortex (RSC) is part of the HD circuit and contains neurons that express multiple spatial signals, including a pattern of bipolar directional tuning – as recently reported in rats exploring a rotationally symmetric two-compartment space. This suggests an unexplored mechanism of the neural compass. In this thesis, I investigated whether the association between the two-way firing symmetry and twofold environment symmetry reveals a general environment symmetry-encoding property of these RSC neurons. I recorded RSC neurons in environments having onefold, twofold and fourfold symmetry. The current study showed that RSC HD cells maintained a consistent global signal, whereas other RSC directional cells showed multi-fold symmetric firing patterns that reflected environment symmetry, not just globally (across all sub-compartments) but also locally (within each sub-compartment). The analyses also showed that the pattern was independent of egocentric boundary vector coding but represented an allocentric spatial code. It means that these RSC cells use environmental cues to organise multiple singular tuning curves which sometimes are combined to form a multidirectional pattern, likely via an interaction with the global HD signal. Thus, both local and global environment symmetry are encoded by local firing patterns in subspaces. This interestingly suggests cognitive mapping and abstraction of space beyond immediate perceptual bounds in RSC. The data generated from this study provides important insights for modelling of direction computation. Taken together, I discuss how having two types of direction codes in RSC may help us to orient more accurately and flexibly in complex and ambiguous space