Distinct descending motor cortex pathways and their roles in movement, bioRxiv, 2017-12-06
ABSTRACTActivity in motor cortex predicts specific movements, seconds before they are initiated. This preparatory activity has been observed in L5 descending ‘pyramidal tract’ (PT) neurons. A key question is how preparatory activity can be maintained without causing movement, and how preparatory activity is eventually converted to a motor command to trigger appropriate movements. We used single cell transcriptional profiling and axonal reconstructions to identify two types of PT neuron. Both types share projections to multiple targets in the basal ganglia and brainstem. One type projects to thalamic regions that connect back to motor cortex. In a delayed-response task, these neurons produced early preparatory activity that persisted until the movement. The second type projects to motor centers in the medulla and produced late preparatory activity and motor commands. These results indicate that two motor cortex output neurons are specialized for distinct roles in motor control.
biorxiv neuroscience 100-200-users 2017Laminar-specific cortical dynamics in human visual and sensorimotor cortices, bioRxiv, 2017-11-29
AbstractLower frequency, feedback, activity in the alpha and beta range is thought to predominantly originate from infragranular cortical layers, whereas feedforward signals in the gamma range stem largely from supragranular layers. Distinct anatomical and spectral channels may therefore play specialized roles in communication within hierarchical cortical networks; however, empirical evidence for this organization in humans is limited. We leverage high precision MEG to test this proposal, directly and non-invasively, in human participants during visually guided actions. Visual alpha activity mapped onto deep cortical laminae, whereas visual gamma activity predominantly arose from superficial laminae. This laminar-specificity was echoed in sensorimotor beta and gamma activity. Visual gamma activity scaled with task demands in a way compatible with feedforward signaling. For sensorimotor activity, we observed a more complex relationship with feedback and feedforward processes. Distinct frequency channels thus operate in a laminar-specific manner, but with dissociable functional roles across sensory and motor cortices.
biorxiv neuroscience 100-200-users 2017Estimating the number of missing experiments in a neuroimaging meta-analysis, bioRxiv, 2017-11-28
AbstractCoordinate-based meta-analyses (CBMA) allow researchers to combine the results from multiple fMRI studies with the goal of obtaining results that are more likely to generalise. However, the interpretation of CBMA findings can be impaired by the file drawer problem, a type of publications bias that refers to studies that are carried out but are not published due to lack of significance. Using foci per contrast count data from the BrainMap database, we propose a zero-truncated modelling approach that allows us to estimate the prevalence of non-significant contrasts. We validate our method with simulations and real coordinate data generated from the Human Connectome Project. Application of our method to the data from BrainMap provides evidence for the existence of a file drawer effect, with the rate of missing contrasts estimated as at least 6 per 100 reported.
biorxiv neuroscience 0-100-users 2017Estimating the prevalence of missing experiments in a neuroimaging meta-analysis, bioRxiv, 2017-11-28
AbstractCoordinate-based meta-analyses (CBMA) allow researchers to combine the results from multiple fMRI experiments with the goal of obtaining results that are more likely to generalise. However, the interpretation of CBMA findings can be impaired by the file drawer problem, a type of publications bias that refers to experiments that are carried out but are not published. Using foci per contrast count data from the BrainMap database, we propose a zero-truncated modelling approach that allows us to estimate the prevalence of non-significant experiments. We validate our method with simulations and real coordinate data generated from the Human Connectome Project. Application of our method to the data from BrainMap provides evidence for the existence of a file drawer effect, with the rate of missing experiments estimated as at least 6 per 100 reported.
biorxiv neuroscience 0-100-users 2017Prioritized memory access explains planning and hippocampal replay, bioRxiv, 2017-11-28
AbstractTo make decisions, animals must evaluate outcomes of candidate choices by accessing memories of relevant experiences. Yet little is known about which experiences are considered or ignored during deliberation, which ultimately governs choice. Here, we propose a normative theory to predict which memories should be accessed at each moment to optimize future decisions. Using nonlocal “replay” of spatial locations in hippocampus as a window into memory access, we simulate a spatial navigation task where an agent accesses memories of locations sequentially, ordered by utility how much extra reward would be earned due to the computation enabling better choices. This prioritization balances two desiderata the need to evaluate imminent choices, vs. the gain from propagating newly encountered information to predecessor states. We show that this theory offers a unifying account of a range of hitherto disconnected findings in the place cell literature such as the balance of forward and reverse replay, biases in the replayed content, and effects of experience. Accordingly, various types of nonlocal events during behavior and rest are re-interpreted as instances of a single choice evaluation operation, unifying seemingly disparate proposed functions of replay including planning, learning and consolidation, and whose dysfunction may underlie pathologies like rumination and craving.
biorxiv neuroscience 0-100-users 2017A suite of transgenic driver and reporter mouse lines with enhanced brain cell type targeting and functionality, bioRxiv, 2017-11-26
SUMMARYModern genetic approaches are powerful in providing access to diverse types of neurons within the mammalian brain and greatly facilitating the study of their function. We here report a large set of driver and reporter transgenic mouse lines, including 23 new driver lines targeting a variety of cortical and subcortical cell populations and 26 new reporter lines expressing an array of molecular tools. In particular, we describe the TIGRE2.0 transgenic platform and introduce Cre-dependent reporter lines that enable optical physiology, optogenetics, and sparse labeling of genetically-defined cell populations. TIGRE2.0 reporters broke the barrier in transgene expression level of single-copy targeted-insertion transgenesis in a wide range of neuronal types, along with additional advantage of a simplified breeding strategy compared to our first-generation TIGRE lines. These novel transgenic lines greatly expand the repertoire of high-precision genetic tools available to effectively identify, monitor, and manipulate distinct cell types in the mouse brain.
biorxiv neuroscience 200-500-users 2017