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Gillis, R.

Publications and source records attributed to Gillis, R..

6 recordsLinked to original sources

Moving object generates topographic responses in the majority of entorhinal neurons

Vision is crucial in generating a complex array of responses in rodents during spatial exploration and in humans during memory tasks. These tasks involve other variables too, e.g. multisensory cues in rodents and complex memories in humans. Further, there are major differences between the medial and lateral entorhinal cortical (MEC and LEC) functional cell types. To understand the contribution of purely visual information to entorhinal responses, we presented a simple, moving vertical bar of light to head-fixed mice, without any task or reward. Surprisingly, 66% (2391/3601) of the MEC broad spiking neurons were significantly modulated by the bar position on the screen. Visual tuning in MEC had a pronounced dorsoventral topography --the tuning strength dropped from 79% in the dorsal most quartile to 40% in the ventral most quartile. Unlike major differences in spatial and other codes between MEC and LEC during free foraging experiments, LEC cells showed very similar visual tuning (392/606, 65%), including the dorso-ventral gradient in LEC5. Additionally, the majority of putative interneurons, from MEC as well as LEC, showed similar, widespread visual tuning, unlike spatial tasks. Neurons also encoded the object motion direction (naso-temporal vs. temporo-nasal visual motion) with changes in mean rate, tuning strength and/or tuning location. Such directional nature of visual tuning indicates significant history-dependence or sequence encoding. Consistently, replacing the continuous motion by randomly flashing bar of light abolished bar-tuning in two-thirds of continuous bar-tuned cells and substantially altered tuning in the rest. These results reveal the contribution of purely visual inputs in generating anatomically organized responses in the majority of entorhinal neurons. The prevalence and similarity of visual tuning across all layers of MEC as well as LEC exceeds that of other known functional cell types (like grid cells in MEC or egocentric object tuning/time-cells in LEC) during spatial navigation tasks and could be foundational in understanding entorhinal complexity.

neuroscience↗

Psilocybin collapses visual change detection and drives cortical dynamics toward a state of surprise

Psilocybin profoundly alters visual perception, yet the neuronal mechanisms underlying these effects remain unclear. Here we combined large-scale Neuropixels recordings with cell-type specific optogenetics in head-fixed mice performing a visual change-detection task. Psilocybin severely impaired task performance without overt motor deficits. In cortex, the drug modestly suppressed activity of layer 5 neurons while preserving representations of image identity. By contrast, psilocybin imposed a 4-Hz oscillation on visually evoked activity that preferentially affected neurons encoding image change rather than image identity. Under psilocybin, expected image repetitions aberrantly recruited change-encoding ensembles and shifted cortical population dynamics towards trajectories normally evoked by genuine stimulus changes. These effects were strongest in somatostatin-expressing (SST) interneurons in visual cortex. The strength of this modulation depended on image structure and was greatest for images with clear, continuous contours, which preferentially recruited change-encoding ensembles. These findings demonstrate that psilocybin drives internally generated cortical surprise signals, providing a circuit mechanism for altered perception in the acute psychedelic state.

neuroscience↗

Map of spiking activity underlying change detection in the mouse visual system

Visual behavior requires coordinated activity across hierarchically organized brain circuits. Understanding this complexity demands datasets that are both large-scale (sampling many areas) and dense (recording many neurons in each area). Here we present a database of spiking activity across the mouse visual system--including thalamus, cortex, and midbrain--while mice perform an image change detection task. Using Neuropixels probes, we record from >75,000 high-quality units in 54 mice, mapping area-, cortical layer-, and cell type-specific coding of sensory and motor information. Modulation by task-engagement increased across the thalamocortical hierarchy but was strongest in the midbrain. Novel images modulated cortical (but not thalamic) responses through delayed recurrent activity. Population decoding and optogenetics identified a critical decision window for change detection and revealed that mice use an adaptation-based rather than image-comparison strategy. This comprehensive resource provides a valuable substrate for understanding sensorimotor computations in neural networks.

neuroscience↗

Stimulus history, not expectation, drives sensory prediction errors in mammalian cortex

Hierarchical predictive coding (HPC) models have recently flourished in neuroscience1-9. Feedforward and feedback processing are at the heart of HPC models. Previous experimental studies using fMRI, EEG/MEG, and LFP9-11 do not reliably resolve feedback modulation from local computations and feedforward outputs. Here, using open-science8, multi-species, multi-area, high-density12, laminar neurophysiology13, we empirically test whether hierarchical predictive coding is a key component shaping cortical processing of visual stimuli. To isolate visual information processing and eliminate motor/reward confounders9-11, we use a no-report task. Our task leveraged so-called global oddballs (GO) as unpredictable, deviant stimuli that circumvent low-level adaptation. We examined their responses relative to local oddballs (LO) that we habituated into highly predictable priors. Four surprising findings in this dataset challenge many existing hierarchical predictive coding models. First, GO responses were exclusive to higher-order, more cognitive areas rather than early-to-mid visual cortex. Second, inhibitory interneuron-targeted optogenetics in primates and mice and waveform shape analysis in primates revealed no evidence that predictive suppression was implemented via these interneurons. Third, highly predictable LO responses dominated in over 50% of all neurons, including in higher-order cortex, which should have anticipated them, indicating limited evidence for predictive suppression. Lastly, prediction error responses evoked by GOs did not evoke feedforward processing. These results reveal circuit dynamics that govern how prediction shapes visual processing, motivating more neurally constrained predictive processing models.

neuroscience↗

SHIELD: Skull-shaped hemispheric implants enabling large-scale-electrophysiology datasets in the mouse brain

To understand the neural basis of behavior, it is essential to measure spiking dynamics across many interacting brain regions. While new technologies, such as Neuropixels probes, facilitate multi-regional recordings, significant surgical and procedural hurdles remain for these experiments to achieve their full potential. Here, we describe a novel 3D-printed cranial-replacement implant (SHIELD) enabling electrophysiological recordings from distributed areas of the mouse brain. This skull-shaped implant is designed with customizable insertion holes, allowing dozens of cortical and subcortical structures to be recorded in a single mouse using repeated multi-probe insertions over many days. We demonstrate the procedures high success rate, biocompatibility, lack of adverse effects on behavior, and compatibility with imaging and optogenetics. To showcase the scientific utility of the SHIELD implant, we use multi-probe recordings to reveal novel insights into how alpha rhythms organize spiking activity across visual and sensorimotor networks. Overall, this method enables powerful large-scale electrophysiological measurements for the study of distributed brain computation.

neuroscience↗

The medial prefrontal cortex during flexible decisions: Evidence for its role in distinct working memory processes

During decisions that involve working memory, task-related information must be encoded, maintained across delays, and retrieved. Few studies have attempted to causally disambiguate how different brain structures contribute to each of these components of working memory. In the present study, we used transient optogenetic disruptions of rat medial prefrontal cortex (mPFC) during a serial spatial reversal learning (SSRL) task to test its role in these specific working memory processes. By analyzing numerous performance metrics, we found: 1) mPFC disruption impaired performance during only the choice epoch of initial discrimination learning of the SSRL task, 2) mPFC disruption impaired performance in dissociable ways across all task epochs (delay, choice, return) during flexible decision-making, 3) mPFC disruption resulted in a reduction of the typical vicarious-trial-and-error (VTE) rate modulation that was related to changes in task demands. Taken together, these findings suggest that the mPFC plays an outsized role in working memory retrieval, becomes involved in encoding and maintenance when recent memories conflict with task demands, and enables animals to flexibly utilize working memory to update behavior as environments change.

neuroscience↗