Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2020.09.16.298539

Effective connectivity and spatial selectivity-dependent fMRI changes elicited by microstimulation of pulvinar and LIP

Kagan, I.·Gibson, L.·Spanou, E.·Wilke, M.
View original source ↗Export metadata ↓

Abstract

The thalamic pulvinar and the lateral intraparietal area (LIP) share reciprocal anatomical connections and are part of an extensive cortical and subcortical network involved in spatial attention and oculomotor processing. The goal of this study was to compare the effective connectivity of dorsal pulvinar (dPul) and LIP and to probe the dependency of microstimulation effects on task demands and spatial tuning properties of a given brain region. To this end, we applied unilateral electrical microstimulation in the dPul (mainly medial pulvinar) and LIP in combination with event-related BOLD fMRI in monkeys performing fixation and memory-guided saccade tasks. Microstimulation in both dPul and LIP enhanced task-related activity in monosynaptically-connected fronto-parietal cortex and along the superior temporal sulcus (STS) including putative face patch locations, as well as in extrastriate cortex. LIP microstimulation elicited strong activity in the opposite homotopic LIP while no homotopic activation was found with dPul stimulation. Both dPul and LIP stimulation also elicited activity in several heterotopic cortical areas in the opposite hemisphere, implying polysynaptic propagation of excitation. Despite extensive activation along the intraparietal sulcus evoked by LIP stimulation, there was a difference in frontal and occipital connectivity elicited by posterior and anterior LIP stimulation sites. Comparison of dPul stimulation with the adjacent but functionally dissimilar ventral pulvinar also showed distinct connectivity. On the level of single trial timecourses within each region of interest (ROI), most ROIs did not show task-dependence of stimulation-elicited response modulation. Across ROIs, however, there was an interaction between task and stimulation, and task-specific correlations between the initial spatial selectivity and the magnitude of stimulation effect were observed. Consequently, stimulation-elicited modulation of task-related activity was best fitted by an additive model scaled down by the initial response amplitude. In summary, we identified overlapping and distinct patterns of thalamocortical and corticocortical connectivity of pulvinar and LIP, highlighting the dorsal bank and fundus of STS as a prominent node of shared circuitry. Spatial task-specific and partly polysynaptic modulations of cue and saccade planning delay period activity in both hemispheres exerted by unilateral pulvinar and parietal stimulation provide insight into the distributed interhemispheric processing underlying spatial behavior. HighlightsO_LIElectrical stimulation of pulvinar and LIP was used to study fMRI effective connectivity C_LIO_LIBoth regions activated prefrontal cortex and the dorsal bank of superior temporal sulcus C_LIO_LIActivations within and across hemispheres suggest polysynaptic propagation C_LIO_LIStimulation effects show interactions between task- and spatial selectivity C_LIO_LIStimulation effects are best fitted by an additive model scaled by the initial response C_LI

Source connections

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Kagan, I., Gibson, L., Spanou, E., Wilke, M.. 2020-09-17. Effective connectivity and spatial selectivity-dependent fMRI changes elicited by microstimulation of pulvinar and LIP. https://doi.org/10.1101/2020.09.16.298539

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Epidermal Langerhans Cells Act as Neuroimmune Regulators of Pain and Itch

Neuroimmune interactions in the skin coordinate immune defense and somatosensory perception, yet how immune cells shape sensory signaling remains poorly defined. Here, we show that Langerhans cells (LCs), epidermal antigen-presenting cells, function as local immune-derived amplifiers of cutaneous sensory signaling. Anatomical and transcriptomic analyses reveal preferential LC association with non-peptidergic sensory neurons. LC activation increases neuronal and behavioral responses to thermal, mechanical, and pruritic stimuli without directly exciting sensory neurons, whereas LC inhibition or ablation selectively reduces pruritogen-evoked itch. We identified semaphorin 7A as a candidate LC-expressed mediator. Semaphorin 7A sensitized cultured sensory neurons to chloroquine and histamine, and neutralizing semaphorin 7A abolished the increase in chloroquine-evoked scratching produced by LC activation. Its receptor PlexinC1 was expressed by most MrgprA3 pruriceptors and blocking PlexinC1 reduced semaphorin 7A-evoked neuronal responses. Together, these findings identify epidermal LCs as local immune-derived amplifiers that regulate the responsiveness of cutaneous sensory circuits and identify semaphorin 7A as a mediator of LC-induced itch potentiation.

neuroscience↗
bioRxiv2026

Feasible closed-loop stimulation for neural latent dynamics control

Modern neuroscience benefits from powerful computational and experimental methods for studying neural populations, including latent dynamics models that predict behavior with few dimensions. But despite their explanatory utility, latent factors are seldom targeted explicitly with experimental perturbations, leaving causal relationships to behavior and inferred dynamical landscapes untested. A promising solution is closed-loop, multi-channel optogenetic control, which, when paired with model predictions, could steer neural trajectories in real time--a feat impossible for traditional, hand-designed stimulation. However, because closed-loop latent control has not been demonstrated in vivo, the hardware and software requirements remain unclear--particularly the necessary stimulation dimensionality and how limited resources such as implant volume and bandwidth should be allocated between stimulation and recording capabilities. Preliminary experiments would thus help guide ongoing technological development. As large-scale exploration of these design spaces in vivo is prohibitively expensive, we conducted a high-throughput simulation survey using biophysically grounded spiking neural networks. We found that low-dimensional actuation is sufficient: in the reference configuration, ~20% of the stimulation channels achieved ~85% of peak control performance, far fewer than the number of neurons. Furthermore, allocating channels roughly equally between stimulation and recording optimized behavioral control, whereas pairing many electrodes with a single light source--the prevailing practice in experimental labs--performed poorly. Even without heavily optimizing modeling or control, we obtained >60% tracking error reduction and >90% evoked behavior accuracy on average for optimal channel counts. These results held across extensive parameter variations, suggesting that closed-loop latent control is feasible with accessible channel counts and establishing design principles for future tool development and in vivo experiments.

neuroscience↗
bioRxiv2026

Identification of Kinome Biomarkers and Therapeutic Rescue in cGMP-Linked Retinal Degeneration

Inherited retinal degenerations, such as Retinitis Pigmentosa (RP) and Leber's congenital amaurosis (LCA), are major causes of progressive and irreversible vision loss. The large number of genes associated with these disorders makes their clinical and molecular characterization difficult, while systemic biomarkers for disease progression or treatment response remain limited. These challenges were addressed by targeting cGMP-associated mechanisms shared by RP and LCA and integrating systemic biomarker profiling with retinal outcomes. Kinase activity analysis (kinome analysis) in peripheral blood mononuclear cells distinguished healthy and diseased states and captured therapy-associated signatures in rd10 mice treated with LP-CN03, a liposomal formulation of the cGMP analog CN03. This first systemic analysis in a therapeutically responsive animal model highlights kinome analysis as a potential translational readout. Given shared cGMP signaling in RP and AIPL1-associated LCA, LP-CN03's therapeutic potential was further evaluated in a new CRISPR-Cas9-generated Aipl1-/- mouse model. Treatment with LP-CN03 preserved retinal structure and function, as shown by electroretinography, longitudinal optical coherence tomography, fundus imaging, optomotor testing, and photoreceptor-specific gene expression. Together, these findings provide independent in vivo evidence for the neuroprotective effect of LP-CN03 in both cGMP-related RP and LCA, also highlighting the translational value of kinome profiling.

neuroscience↗