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Lecoq, J. A.

Publications and source records attributed to Lecoq, J. A..

4 recordsLinked to original sources

Increased activity without changes in coupling between somata and apical dendrites during visual mismatches

Leading theories of cortical function posit that sensory processing involves a comparison between top-down predictions and bottom-up sensory data. Tests of these theories have been hampered by experimental challenges related to simultaneously recording top-down and bottom-up signals in response to sensory stimuli that either do or do not match internally-generated predictions. Here, we conduct dual-plane 2-photon calcium imaging near-simultaneously from distal apical dendrites and somata of pyramidal neurons in each of 4 different regions of mouse visual cortex while the mice are presented with visual sequences that can either match or mismatch previously habituated visual stimuli. Specifically, we examine the responses in the distal apical dendrites and cell bodies of pyramidal neurons while mice view either movie clips that reverse unexpectedly or Gabor patch sequences that have orientations that do not match habituated patterns. We find that in response to unexpected reversals in natural movies, both the apical dendrites and somata show increased activity that decreases over repeated exposures, consistent with a prediction error response. However, we do not find any clear evidence for increased activity in response to mismatches in Gabor sequences, beyond possible release from adaptation effects. We additionally use volumetric images to connect dendritic and somatic compartments and examine the coupling between connected dendrites and cell bodies in layer 5 pyramidal neurons. We do not find evidence for changes in coupling in response to mismatch stimuli, either for natural movies or Gabor sequences. Our results are consistent across four regions of visual cortex. We also observe that increased responses to reversals in natural movies are stronger in layer 2/3 than layer 5 pyramidal neurons. Altogether, these data suggest that visual cortex is sensitive to deviations from previously-experienced naturalistic inputs. Our data do not suggest that this mismatch sensitivity extends to artificial stimuli, nor do they support theories of prediction error causing changes in the coupling between apical dendrites and somata.

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↗

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↗

VIP interneurons selectively enhance weak but behaviorally-relevant stimuli.

Vasoactive intestinal peptide-expressing (VIP) interneurons in cortex regulate feedback inhibition of pyramidal neurons through suppression of somatostatin-expressing (SST) interneurons and, reciprocally, SST neurons inhibit VIP neurons. Here, we show that VIP neurons in mouse primary visual cortex have complementary contrast tuning to SST neurons and respond synergistically to front-to-back visual motion and locomotion. Network modeling indicates that this VIP-SST mutual antagonism regulates the gain of cortex to achieve both sensitivity to behaviorally-relevant stimuli and network stability.

neuroscience↗