Biology subjects

Ha, V.

Publications and source records attributed to Ha, V..

6 recordsLinked to original sources

bioRxiv2026

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↗

bioRxiv2026

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↗

bioRxiv2024

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↗

bioRxiv2023

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↗

bioRxiv2023

Recurrent pattern completion drives the neocortical representation of sensory inference

When sensory information is incomplete or ambiguous, the brain relies on prior expectations to infer perceptual objects. Despite the centrality of this process to perception, the neural mechanism of sensory inference is not known. Illusory contours (ICs) are key tools to study sensory inference because they contain edges or objects that are implied only by their spatial context. Using cellular resolution, mesoscale two-photon calcium imaging and multi-Neuropixels recordings in the mouse visual cortex, we identified a sparse subset of neurons in the primary visual cortex (V1) and higher visual areas that respond emergently to ICs. We found that these highly selective IC-encoders mediate the neural representation of IC inference. Strikingly, selective activation of these neurons using two-photon holographic optogenetics was sufficient to recreate IC representation in the rest of the V1 network, in the absence of any visual stimulus. This outlines a model in which primary sensory cortex facilitates sensory inference by selectively strengthening input patterns that match prior expectations through local, recurrent circuitry. Our data thus suggest a clear computational purpose for recurrence in the generation of holistic percepts under sensory ambiguity. More generally, selective reinforcement of top-down predictions by pattern-completing recurrent circuits in lower sensory cortices may constitute a key step in sensory inference.

neuroscience↗

bioRxiv2021

Toxoplasma infection alters dopamine-sensitive behaviors and host gene expression patterns associated with neuropsychiatric disease

Toxoplasma gondii is a single celled parasite thought to infect 1 in 3 worldwide. During chronic infection, T. gondii can migrate to the brain where it promotes low-grade neuroinflammation with the capacity to induce changes in brain morphology and behavior. Consequently, infection with T. gondii has been linked with a number of neurocognitive disorders including schizophrenia (SZ), dementia, and Parkinsons disease. Beyond neuroinflammation, infection with T. gondii can modulate the production of neurotransmitters, such as dopamine. To further dissect these pathways and examine the impact of altered dopaminergic sensitivity in T. gondii-infected mice on both behavior and gene expression, we developed a novel mouse model, based on stimulant-induced (cocaine) hyperactivity. Employing this model, we found that infection with T. gondii did not alter fear behavior but did impact motor activity and neuropsychiatric-related behaviurs. While both behaviors may help reduce predator avoidance, consistent with previous studies, the latter finding is reminiscent of neurocognitive disorders. Applying RNASeq to two relevant brain regions, striatum and hippocampus, we identified a broad upregulation of immune responses. However, we also noted significant associations with more meaningful neurologically relevant terms were masked due to the sheer number of terms incorporated in multiple testing correction. We therefore performed a more focused analysis using a curated set of neurologically relevant terms revealing significant associations across multiple pathways. We also found that T. gondii and cocaine treatments impacted the expression of similar functional pathways in the hippocampus and striatum although, as indicated by the low overlap among differentially expressed genes, largely via different proteins. Furthermore, while most differentially expressed genes reacted to a single condition and were mostly upregulated, we identified gene expression patterns indicating unexpected interactions between T. gondii infection and cocaine exposure. These include sets of genes which responded to cocaine exposure but not upon cocaine exposure in the context of T. gondii infection, suggestive of a neuroprotective effect advantageous to parasite persistence. Given its ability to uncover such complex relationships, we propose this novel model offers a new perspective to dissect the molecular pathways by which T. gondii infection contributes to neuropsychiatric disorders such as schizophrenia.

microbiology↗