A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

Models of Neocortical Layer 5b Pyramidal Cells Capturing a Wide Range of Dendritic and Perisomatic Active Properties

The thick-tufted layer 5b pyramidal cell extends its dendritic tree to all six layers of the mammalian neocortex and serves as a major building block for the cortical column. L5b pyramidal cells have been the subject of extensive experimental and modeling studies, yet conductance-based models of these cells that faithfully reproduce both their perisomatic Na+-spiking behavior as well as key dendritic active properties, including Ca2+ spikes and back-propagating action potentials, are still lacking. Based on a large body of experimental recordings from both the soma and dendrites of L5b pyramidal cells in adult rats, we characterized key features of the somatic and dendritic firing and quantified their statistics. We used these features to constrain the density of a set of ion channels over the soma and dendritic surface via multi-objective optimization with an evolutionary algorithm, thus generating a set of detailed conductance-based models that faithfully replicate the back-propagating action potential activated Ca2+ spike firing and the perisomatic firing response to current steps, as well as the experimental variability of the properties. Furthermore, we show a useful way to analyze model parameters with our sets of models, which enabled us to identify some of the mechanisms responsible for the dynamic properties of L5b pyramidal cells as well as mechanisms that are sensitive to morphological changes. This automated framework can be used to develop a database of faithful models for other neuron types. The models we present provide several experimentally-testable predictions and can serve as a powerful tool for theoretical investigations of the contribution of single-cell dynamics to network activity and its computational capabilities

Whisker Movements Reveal Spatial Attention: A Unified Computational Model of Active Sensing Control in the Rat

Spatial attention is most often investigated in the visual modality through measurement of eye movements, with primates, including humans, a widely-studied model. Its study in laboratory rodents, such as mice and rats, requires different techniques, owing to the lack of a visual fovea and the particular ethological relevance of orienting movements of the snout and the whiskers in these animals. In recent years, several reliable relationships have been observed between environmental and behavioural variables and movements of the whiskers, but the function of these responses, as well as how they integrate, remains unclear. Here, we propose a unifying abstract model of whisker movement control that has as its key variable the region of space that is the animal's current focus of attention, and demonstrate, using computer-simulated behavioral experiments, that the model is consistent with a broad range of experimental observations. A core hypothesis is that the rat explicitly decodes the location in space of whisker contacts and that this representation is used to regulate whisker drive signals. This proposition stands in contrast to earlier proposals that the modulation of whisker movement during exploration is mediated primarily by reflex loops. We go on to argue that the superior colliculus is a candidate neural substrate for the siting of a head-centred map guiding whisker movement, in analogy to current models of visual attention. The proposed model has the potential to offer a more complete understanding of whisker control as well as to highlight the potential of the rodent and its whiskers as a tool for the study of mammalian attention

Terminations of reticulospinal fibers originating from the gigantocellular reticular formation in the mouse spinal cord.

The present study investigated the projections of the gigantocellular reticular nucleus (Gi) and its neighbors—the dorsal paragigantocellular reticular nucleus (DPGi), the alpha/ventral part of the gigantocellular reticular nucleus (GiA/V), and the lateral paragigantocellular reticular nucleus (LPGi)—to the mouse spinal cord by injecting the anterograde tracer biotinylated dextran amine (BDA) into the Gi, DPGi, GiA/GiV, and LPGi. The Gi projected to the entire spinal cord bilaterally with an ipsilateral predominance. Its fibers traveled in both the ventral and lateral funiculi with a greater presence in the ventral funiculus. As the fibers descended in the spinal cord, their density in the lateral funiculus increased. The terminals were present mainly in laminae 7–10 with a dorsolateral expansion caudally. In the lumbar and sacral cord, a considerable number of terminals were also present in laminae 5 and 6. Contralateral fibers shared a similar pattern to their ipsilateral counterparts and some fibers were seen to cross the midline. Fibers arising from the DPGi were similarly distributed in the spinal cord except that there was no dorsolateral expansion in the lumbar and sacral segments and there were fewer fiber terminals. Fibers arising from GiA/V predominantly traveled in the ventral and lateral funiculi ipsilaterally. Ipsilaterally, the density of fibers in the ventral funiculus decreased along the rostrocaudal axis, whereas the density of fibers in the lateral funiculus increased. They terminate mainly in the medial ventral horn and lamina 10 with a smaller number of fibers in the dorsal horn. Fibers arising from the LPGi traveled in both the ventral and lateral funiculi and the density of these fibers in the ventral and lateral funiculi decreased dramatically in the lumbar and sacral segments. Their terminals were present in the ventral horn with a large portion of them terminating in the motor neuron columns. The present study is the first demonstration of the termination pattern of fibers arising from the Gi, DPGi, GiA/GiV, and LPGi in the mouse spinal cord. It provides an anatomical foundation for those who are conducting spinal cord injury and locomotion related research