An individual interneuron participates in many kinds of inhibition and spans much of the mouse visual thalamus, bioRxiv, 2019-06-27
SUMMARYIn principle, one way to define the functional role of a neuron would be to identify all the synaptic input it receives and all synaptic output it confers onto its targets. With serial electron microscopy we annotated all the input synapses (862) and output synapses (626) associated with one inhibitory interneuron in the visual thalamus of the mouse. This neuron’s neurites covered a broad swath of lateral geniculate nucleus and spanned multiple functionally distinct regions. Every one of its neurites formed synapses onto hundreds of thalamocortical cells of several different types. All but one small neurite also had dendrite-like properties and received input from retinal ganglion cell axons. Pre- and postsynaptic associations with other inhibitory interneurons were also distributed throughout the interneuron’s territory. We observed a diverse array of local synaptic motifs and three fundamentally different types of inhibitory neurites. Many thalamocortical cells were innervated weakly by this interneuron by single en passant shaft synapses. But a subset of the interneuron’s thalamocortical cell targets received multiple synaptic inputs from targeted inhibitory neurites that climbed along the thalamocortical cell’s dendrite with an assemblage of fasciculated retinal ganglion cell axons. Because of the diverse range of synaptic relationships exhibited by this one neuron, this cell defies a single functional label and seems rather to be using extremely local synaptic processing to participate in many different functions.
biorxiv neuroscience 100-200-users 2019Astrocytes Contribute to Remote Memory Formation by Modulating Hippocampal-Cortical Communication During Learning, bioRxiv, 2019-06-27
ABSTRACTThe consolidation and retrieval of remote memories depend on the coordinated activity of the hippocampus and frontal cortices. However, the exact time at which these regions are recruited to support memory and the interactions between them are still debated. Astrocytes can sense and modify neuronal activity with great precision, but their role in cognitive function has not been extensively explored. To investigate the role of astrocytes in remote memory we expressed the Gi-coupled receptor hM4Di in CA1 astrocytes, allowing their manipulation by a designer drug. We discovered that astrocytic modulation during learning resulted in a specific impairment in remote, but not recent, memory recall, accompanied by decreased neuronal activity in the anterior cingulate cortex (ACC) during retrieval. We revealed a massive recruitment of ACC-projecting neurons in CA1 during memory acquisition, accompanied by activation of ACC neurons. Astrocytic Gi activation disrupted CA3 to CA1 communication in-vivo, and reduced the downstream response in the ACC. This same manipulation in behaving mice induced a projection-specific inhibition of ACC-projecting CA1 neurons during learning, consequently preventing the recruitment of the ACC. Our findings suggest that the foundation of remote memory is established in the ACC during acquisition, engaging a distinct process from the one supporting consolidation of recent memory. Furthermore, the mechanism underlying remote memory involves projection-specific functions of astrocytes in regulating neuronal activity.
biorxiv neuroscience 100-200-users 2019What is the test-retest reliability of common task-fMRI measures? New empirical evidence and a meta-analysis, bioRxiv, 2019-06-25
AbstractIdentifying brain biomarkers of disease risk is a growing priority in neuroscience. The ability to identify meaningful biomarkers is limited by measurement reliability; unreliable measures are unsuitable for predicting clinical outcomes. Measuring brain activity using task-fMRI is a major focus of biomarker development; however, the reliability of task-fMRI has not been systematically evaluated. We present converging evidence demonstrating poor reliability of task-fMRI measures. First, a meta-analysis of 90 experiments (N=1,008) revealed poor overall reliability (mean ICC=.397). Second, the test-retest reliabilities of activity in a priori regions of interest across 11 common fMRI tasks collected in the context of the Human Connectome Project (N=45) and the Dunedin Study (N=20) were poor (ICCs=.067-.485). Collectively, these findings demonstrate that common task-fMRI measures are not currently suitable for brain biomarker discovery or individual differences research. We review how this state of affairs came to be and highlight avenues for improving task-fMRI reliability.
biorxiv neuroscience 200-500-users 2019Brain state stability during working memory is explained by network control theory, modulated by dopamine D1D2 receptor function, and diminished in schizophrenia, bioRxiv, 2019-06-23
Dynamical brain state transitions are critical for flexible working memory but the network mechanisms are incompletely understood. Here, we show that working memory entails brain-wide switching between activity states. The stability of states relates to dopamine D1 receptor gene expression while state transitions are influenced by D2 receptor expression and pharmacological modulation. Schizophrenia patients show altered network control properties, including a more diverse energy landscape and decreased stability of working memory representations.
biorxiv neuroscience 0-100-users 2019High precision coding in visual cortex, bioRxiv, 2019-06-22
Single neurons in visual cortex provide unreliable measurements of visual features due to their high trial-to-trial variability. It is not known if this “noise” extends its effects over large neural populations to impair the global encoding of stimuli. We recorded simultaneously from ∼20,000 neurons in mouse primary visual cortex (V1) and found that the neural populations had discrimination thresholds of ∼0.34° in an orientation decoding task. These thresholds were nearly 100 times smaller than those reported behaviorally in mice. The discrepancy between neural and behavioral discrimination could not be explained by the types of stimuli we used, by behavioral states or by the sequential nature of perceptual learning tasks. Furthermore, higher-order visual areas lateral to V1 could be decoded equally well. These results imply that the limits of sensory perception in mice are not set by neural noise in sensory cortex, but by the limitations of downstream decoders.
biorxiv neuroscience 500+-users 2019The “creatures” of the human cortical somatosensory system, bioRxiv, 2019-06-22
AbstractPenfield’s description of the “homunculus”, a “grotesque creature” with large lips and hands and small trunk and legs depicting the representation of body-parts within the primary somatosensory cortex (S1), is one of the most prominent contributions to the neurosciences. Since then, numerous studies have identified additional body-parts representations outside of S1. Nevertheless, it has been implicitly assumed that S1’s homunculus is representative of the entire somatosensory cortex. Therefore, the distribution of body-parts representations in other brain regions, the property that gave Penfield’s homunculus its famous “grotesque” appearance, has been overlooked. We used whole-body somatosensory stimulation, functional MRI and a new cortical parcellation to quantify the organization of the cortical somatosensory representation. Our analysis showed first, an extensive somatosensory response over the cortex; and second, that the proportional representation of body-parts differs substantially between major neuroanatomical regions and from S1, with, for instance, much larger trunk representation at higher brain regions, potentially in relation to the regions’ functional specialization. These results extend Penfield’s initial findings to the higher level of somatosensory processing and suggest a major role for somatosensation in human cognition.
biorxiv neuroscience 0-100-users 2019