Specialized and spatially organized coding of sensory, motor, and cognitive variables in midbrain dopamine neurons, bioRxiv, 2018-10-29

There is increased appreciation that dopamine (DA) neurons in the midbrain respond not only to reward 1,2 and reward-predicting cues 1,3,4, but also to other variables such as distance to reward 5, movements 6–11 and behavioral choices 12–15. Based on these findings, a major open question is how the responses to these diverse variables are organized across the population of DA neurons. In other words, do individual DA neurons multiplex multiple variables, or are subsets of neurons specialized in encoding specific behavioral variables? The reason that this fundamental question has been difficult to resolve is that recordings from large populations of individual DA neurons have not been performed in a behavioral task with sufficient complexity to examine these diverse variables simultaneously. To address this gap, we used 2-photon calcium imaging through an implanted lens to record activity of >300 midbrain DA neurons in the VTA during a complex decision-making task. As mice navigated in a virtual reality (VR) environment, DA neurons encoded an array of sensory, motor, and cognitive variables. These responses were functionally clustered, such that subpopulations of neurons transmitted information about a subset of behavioral variables, in addition to encoding reward. These functional clusters were spatially organized, such that neighboring neurons were more likely to be part of the same cluster. Taken together with the topography between DA neurons and their projections, this specialization and anatomical organization may aid downstream circuits in correctly interpreting the wide range of signals transmitted by DA neurons.

biorxiv neuroscience 0-100-users 2018

The architecture of cell differentiation in choanoflagellates and sponge choanocytes, bioRxiv, 2018-10-29

SUMMARYCollar cells are ancient animal cell types which are conserved across the animal kingdom [1] and their closest relatives, the choanoflagellates [2]. However, little is known about their ancestry, their subcellular architecture, or how they differentiate. The choanoflagellate Salpingoeca rosetta [3] expresses genes necessary for animal multicellularity and development [4] and can alternate between unicellular and multicellular states [3,5], making it a powerful model to investigate the origin of animal multicellularity and mechanisms underlying cell differentiation [6,7]. To compare the subcellular architecture of solitary collar cells in S. rosetta with that of multicellular “rosettes” and collar cells in sponges, we reconstructed entire cells in 3D through transmission electron microscopy on serial ultrathin sections. Structural analysis of our 3D reconstructions revealed important differences between single and colonial choanoflagellate cells, with colonial cells exhibiting a more amoeboid morphology consistent with relatively high levels of macropinocytotic activity. Comparison of multiple reconstructed rosette colonies highlighted the variable nature of cell sizes, cell-cell contact networks and colony arrangement. Importantly, we uncovered the presence of elongated cells in some rosette colonies that likely represent a distinct and differentiated cell type. Intercellular bridges within choanoflagellate colonies displayed a variety of morphologies and connected some, but not all, neighbouring cells. Reconstruction of sponge choanocytes revealed both ultrastructural commonalities and differences in comparison to choanoflagellates. Choanocytes and colonial choanoflagellates are typified by high amoeboid cell activity. In both, the number of microvilli and volumetric proportion of the Golgi apparatus are comparable, whereas choanocytes devote less of their cell volume to the nucleus and mitochondria than choanoflagellates and more of their volume to food vacuoles. Together, our comparative reconstructions uncover the architecture of cell differentiation in choanoflagellates and sponge choanocytes and constitute an important step in reconstructing the cell biology of the last common ancestor of the animal kingdom.

biorxiv evolutionary-biology 100-200-users 2018

 

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