Single-cell in situ transcriptomic map of astrocyte cortical layer diversity, bioRxiv, 2018-10-03
AbstractDuring organogenesis, patterns and gradients of gene expression underlie organization and diversified cell specification to generate complex tissue architecture. While the cerebral cortex is organized into six excitatory neuronal layers, it is unclear whether glial cells are diversified to mimic neuronal laminae or show distinct layering. To determine the molecular architecture of the mammalian cortex, we developed a high content pipeline that can quantify single-cell gene expression in situ. The Large-area Spatial Transcriptomic (LaST) map confirmed expected cortical neuron layer organization and also revealed a novel neuronal identity signature. Screening 46 candidate genes for astrocyte diversity across the cortex, we identified grey matter superficial, mid and deep astrocyte identities in gradient layer patterns that were distinct from neurons. Astrocyte layers formed in early postnatal cortex and mostly persisted in adult mouse and human cortex. Mutations that shifted neuronal post-mitotic identity or organization were sufficient to alter glial layering, indicating an instructive role for neuronal cues. In normal mouse cortex, astrocyte layer patterns showed area diversity between functionally distinct cortical regions. These findings indicate that excitatory neurons and astrocytes cells are organized into distinct lineage-associated laminae, which give rise to higher order neuroglial complexity of cortical architecture.
biorxiv neuroscience 0-100-users 2018There is no single functional atlas even for a single individual Parcellation of the human brain is state dependent, bioRxiv, 2018-10-02
AbstractThe goal of human brain mapping has long been to delineate the functional subunits in the brain and elucidate the functional role of each of these brain regions. Recent work has focused on whole-brain parcellation of functional Magnetic Resonance Imaging (fMRI) data to identify these subunits and create a functional atlas. Functional connectivity approaches to understand the brain at the network level require such an atlas to assess connections between parcels and extract network properties. While no single functional atlas has emerged as the dominant atlas to date, there remains an underlying assumption that such an atlas exists. Using fMRI data from a highly sampled subject as well as two independent replication data sets, we demonstrate that functional parcellations based on fMRI connectivity data reconfigure substantially and in a meaningful manner, according to brain state.
biorxiv neuroscience 200-500-users 2018A spatial atlas of inhibitory cell types in mouse hippocampus, bioRxiv, 2018-10-01
Understanding the function of a tissue requires knowing the spatial organization of its constituent cell types. In the cerebral cortex, single-cell RNA sequencing (scRNA-seq) has revealed the genome-wide expression patterns that define its many, closely related cell types, but cannot reveal their spatial arrangement. Here we introduce probabilistic cell typing by in situ sequencing (pciSeq), an approach that leverages prior scRNA-seq classification to identify cell types using multiplexed in situ RNA detection. We applied this method to map the inhibitory neurons of hippocampal area CA1, a cell system critical for memory function, for which ground truth is available from extensive prior work identifying the laminar organization of subtly differing cell types. Our method confidently identified 16 interneuron classes, in a spatial arrangement closely matching ground truth. This method will allow identifying the spatial organization of fine cell types across the brain and other tissues.
biorxiv neuroscience 100-200-users 2018Amygdala neuronal ensembles dynamically encode behavioral states, bioRxiv, 2018-09-25
AbstractInternal states, including affective or homeostatic states, are important behavioral motivators. The amygdala is a key brain region involved in the regulation of motivated behaviors, yet how distinct internal states are represented in amygdala circuits is unknown. Here, by imaging somatic neural calcium dynamics in freely moving mice, we identify changes in the relative activity levels of two major, non-overlapping populations of principal neurons in the basal nucleus of the amygdala (BA) that predict switches between exploratory and non-exploratory (defensive, anxiety-like) behavioral states across different environments. Moreover, the amygdala widely broadcasts internal state information via several output pathways to larger brain networks, and sensory responses in BA occur independently of behavioral state encoding. Thus, the brain processes external stimuli and internal states in an orthogonal manner, which may facilitate rapid and flexible selection of appropriate, state-dependent behavioral responses.
biorxiv neuroscience 0-100-users 2018Layer-dependent activity in human prefrontal cortex during working memory, bioRxiv, 2018-09-24
Working memory involves a series of functions encoding a stimulus, maintaining or manipulating its representation over a delay, and finally making a behavioral response. While working memory engages dorsolateral prefrontal cortex (dlPFC), few studies have investigated whether these subfunctions are localized to different cortical depths in this region, and none have done so in humans. Here, we use high-resolution functional MRI to interrogate the layer specificity of neural activity during different epochs of a working memory task in dlPFC. We detect activity timecourses that follow the hypothesized patterns superficial layers are preferentially active during the delay period, while deeper layers are preferentially active during the response. Results demonstrate that layer-specific fMRI can be used in higher-order brain regions to non-invasively map cognitive information processing along cortical circuitry in humans.
biorxiv neuroscience 0-100-users 2018A Multi-Domain Task Battery Reveals Functional Boundaries in the Human Cerebellum, bioRxiv, 2018-09-21
AbstractThere is compelling evidence that the human cerebellum is engaged in a wide array of motor and cognitive tasks. A fundamental question centers on whether the cerebellum is organized into distinct functional sub-regions. To address this question, we employed a rich task battery, designed to tap into a broad range of cognitive processes. During four functional magnetic resonance imaging (fMRI) sessions, participants performed a battery of 26 diverse tasks comprising 47 unique conditions. Using the data from this multi-domain task battery (MDTB), we derived a comprehensive functional parcellation of the cerebellar cortex and evaluated it by predicting functional boundaries in a novel set of tasks. The new parcellation successfully identified distinct functional sub-regions, providing significant improvements over existing parcellations derived from task-free data. Lobular boundaries, commonly used to summarize functional data, did not coincide with functional subdivisions. This multi-domain task approach offers novel insights into the functional heterogeneity of the cerebellar cortex.
biorxiv neuroscience 100-200-users 2018