Understanding the basis of brain function requires knowledge of cortical operations over wide-spatial scales, but also within the context of single neurons. In vivo, wide-field GCaMP imaging and sub-cortical/cortical cellular electrophysiology were used in mice to investigate relationships between spontaneous single neuron spiking and mesoscopic cortical activity. We make use of a rich set of cortical activity motifs that are present in spontaneous activity in anesthetized and awake animals. A mesoscale spike-triggered averaging procedure allowed the identification of motifs that are preferentially linked to individual spiking neurons by employing genetically targeted indicators of neuronal activity. Thalamic neurons predicted and reported specific cycles of wide-scale cortical inhibition/excitation. In contrast, spike-triggered maps derived from single cortical neurons yielded spatio-temporal maps expected for regional cortical consensus function. This approach can define network relationships between any point source of neuronal spiking and mesoscale cortical maps.
- Timothy H Murphy
- Timothy H Murphy
- Dongsheng Xiao
- Jeff M LeDue
- Timothy H Murphy
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: Animal protocols (A13-0336 and A14-0266) were approved by the University of British Columbia Animal Care Committee and conformed to the Canadian Council on Animal Care and Use guidelines.
- David Kleinfeld, University of California, San Diego, United States
© 2017, Xiao et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
The organization of neural circuits determines nervous system function. Variability can arise during neural circuit development (e.g. neurite morphology, axon/dendrite position). To ensure robust nervous system function, mechanisms must exist to accommodate variation in neurite positioning during circuit formation. Previously we developed a model system in the Drosophila ventral nerve cord to conditionally induce positional variability of a proprioceptive sensory axon terminal, and used this model to show that when we altered the presynaptic position of the sensory neuron, its major postsynaptic interneuron partner modified its dendritic arbor to match the presynaptic contact, resulting in functional synaptic input (Sales et al., 2019). Here we investigate the cellular mechanisms by which the interneuron dendrites detect and match variation in presynaptic partner location and input strength. We manipulate the presynaptic sensory neuron by (a) ablation; (b) silencing or activation; or (c) altering its location in the neuropil. From these experiments we conclude that there are two opposing mechanisms used to establish functional connectivity in the face of presynaptic variability: presynaptic contact stimulates dendrite outgrowth locally, whereas presynaptic activity inhibits postsynaptic dendrite outgrowth globally. These mechanisms are only active during an early larval critical period for structural plasticity. Collectively, our data provide new insights into dendrite development, identifying mechanisms that allow dendrites to flexibly respond to developmental variability in presynaptic location and input strength.
Associations between attention-deficit/hyperactivity disorder (ADHD) and brain morphology have been reported, although with several inconsistencies. These may partly stem from confounding bias, which could distort associations and limit generalizability. We examined how associations between brain morphology and ADHD symptoms change with adjustments for potential confounders typically overlooked in the literature (aim 1), and for the intelligence quotient (IQ) and head motion, which are generally corrected for but play ambiguous roles (aim 2).
Participants were 10-year-old children from the Adolescent Brain Cognitive Development (N = 7722) and Generation R (N = 2531) Studies. Cortical area, volume, and thickness were measured with MRI and ADHD symptoms with the Child Behavior Checklist. Surface-based cross-sectional analyses were run.
ADHD symptoms related to widespread cortical regions when solely adjusting for demographic factors. Additional adjustments for socioeconomic and maternal behavioral confounders (aim 1) generally attenuated associations, as cluster sizes halved and effect sizes substantially reduced. Cluster sizes further changed when including IQ and head motion (aim 2), however, we argue that adjustments might have introduced bias.
Careful confounder selection and control can help identify more robust and specific regions of associations for ADHD symptoms, across two cohorts. We provided guidance to minimizing confounding bias in psychiatric neuroimaging.
Authors are supported by an NWO-VICI grant (NWO-ZonMW: 016.VICI.170.200 to HT) for HT, LDA, SL, and the Sophia Foundation S18-20, and Erasmus University and Erasmus MC Fellowship for RLM.