Biology subjects

Haag, M.

Publications and source records attributed to Haag, M..

5 recordsLinked to original sources

bioRxiv2026

Comparable phosphene size and contrast properties, but differing detection reliability for optogenetic versus electrical stimulation of macaque V1

Cortical visual prostheses aim to restore vision by stimulating primary visual cortex (V1) to evoke artificial percepts (phosphenes). Electrical stimulation has long served this purpose, and optogenetic approaches promise higher spatial resolution via cell-type specificity. Recent investigations have demonstrated localized behavioral responses to optogenetic V1 stimulation (1--3), but the applied perimetry paradigms cannot dissociate a genuine percept from a reflexive oculomotor response, leaving the perceptual character of optogenetic phosphenes unresolved. To address this gap, two macaques received optogenetic V1 injections guided by laminar electrophysiology and performed detection and discrimination tasks under interleaved electrical, optogenetic, and visual stimulation, enabling direct within-subject comparison. Electrical stimulation reliably evoked detectable percepts (positive d' in 100% of sessions), with thresholds scaling with current, resembling visual contrast-response functions. Optogenetic stimulation was far less reliable, with positive d' in only ~50% of sessions, despite confirmed V1 activation. Despite this reliability difference, optogenetically evoked percepts closely resembled electrically and visually evoked percepts in perceptual character: perceived size (~1{degrees} of visual angle) was comparable across conditions and scaled similarly with eccentricity. Similarly, perceived contrast equivalents (5%-11% visual-contrast equivalent) were broadly comparable across stimulation approaches. These findings indicate that successful optogenetic activation engages the same perceptual encoding mechanisms as electrical and natural vision, but that reliable detection may additionally depend on circuit-level mechanisms not consistently engaged by current optogenetic parameters. The comparable percept size further suggests optogenetic stimulation may not confer the enhanced spatial resolution often proposed as its key advantage.

neuroscience↗

bioRxiv2024

Kinetic and structure-based comparisons of silent and stimulatory flagellin interactions with TLR5

The bacterial protein flagellin is the sole ligand of the innate immune receptor Toll- like receptor 5 (TLR5). Flagellins with strong agonism bind TLR5 at their D1 and D0 domains, while poor agonist "silent" flagellins bind with D1 only. However, D0-TLR5 interactions insufficiently explain the silent phenotype. Here, we characterize the D1 domain binding kinetics of the silent flagellin RhFlaB compared to the strong canonical agonist StFliC. Using Surface Plasmon Resonance, we show that the RhFlaB-D1 binds more strongly than StFliC-D1, but forms shorter-lived complexes. Cryo-EM analysis of RhFlaB showed its D1 primary interface (PI) contains two distinct hydrophobic pockets, which should facilitate rapid association, while its D1s secondary interface (SI) is dominated by negatively charged residues, which likely impede residue-residue interactions. Comparisons with an existing StFliC-D1 structure suggest that strong agonism requires strong binding at both the PI and SI of the D1, and silent flagellins evade detection partly through weaker SI interactions. These findings offer a foundation for designing targeted interventions that can modulate TLR5 activity to influence immunity, inflammation, or even gut microbiome composition.

biochemistry↗

bioRxiv2021

Stimulus dependence of theta rhythmic activity in primate V1 and its potential relevance for visual perception

Theta-band (3-8 Hz) neural oscillations are integral to sensory processing and active exploration. Traditionally associated with higher-order areas such as hippocampus and prefrontal cortex, recent studies identified theta rhythmic modulations in the primary visual cortex (V1) of mice during locomotion, suggesting sensory processing functions. Here, we demonstrate that careful optimization of visual stimulus size and contrast can induce robust theta oscillations in macaque V1. During visual detection, monkeys reaction times fluctuated rhythmically at the theta frequency of V1 neural activity, with detection performance correlated to the theta phase. These findings suggest that induced theta oscillations may reflect an intrinsic temporal filtering mechanism of V1 neurons, highlighting the importance of early sensory cortical dynamics in shaping perceptual timing.

neuroscience↗

bioRxiv2021

Optogenetic stimulation of primate V1 reveals local laminar and large-scale cortical networks related to perceptual phosphenes

Developing optogenetics in non-human primates (NHPs) is essential for translating its successful implementation in rodents to clinical applications in humans. However, information about how optogenetics influences the primate cortex remains limited. Here, we evaluate how optogenetic stimulation of the primate primary visual cortex (V1) affects local and large-scale network activation concerned with visual perception. To this end we injected an optogenetic construct (AAV9-hSyn-ChR2-eYFP) into the V1 cortex of four macaque monkeys (macaca mulatta) and measured the effects of optogenetic V1 stimulation using functional magnetic resonance imaging (fMRI), laminar electrophysiology, and behavioural assessment. In three macaques, blood-oxygen-dependent (BOLD) fMRI activity could be reliably elicited with optogenetic stimulation in V1 and several connected extrastriate brain areas, including V2/V3, motion-sensitive area MT and the frontal-eye-fields (FEF), in particular when pulsed stimulation at 40 Hz was applied. BOLD modulation was associated with consistent neural spiking activity measured in V1 of two macaques. More detailed analysis revealed strongest neuronal activation in layer 4B and infragranular layers, which tightly reflected the histological expression pattern of the optogenetic construct in V1. Driving this visual network proved sufficient to elicit a visual percept ( phosphene) in one macaque during a perceptual choice task. Taken together, our findings reveal the laminar and large-cortical activation pattern related to visual phosphene generation and emphasize the need for further improving optogenetic methods in NHPs as a step towards applications in humans.

neuroscience↗

bioRxiv2021

Dynamic reconfiguration of macaque brain networks during free-viewing of natural scenes

Natural vision involves the activation of a wide range of higher-level regions processing objects, motion, faces and actions. Here, we pursue a data-driven approach to explore how higher-level visual processes relate to the underlying structural and functional connectivity. Using a free-viewing paradigm in four awake rhesus macaque monkeys, we investigate how different visual scenes change functional connectivity. Additionally, we explore how such functional connectivity, as measured through fMRI, is related to the structural connectivity, as measured through diffusion weighted imaging. At first, we evaluate the consistency of the elicited free-viewing pattern using standard analytical techniques. We also evaluate the underlying structural connectivity via diffusion data by tracking white matter bundle projections from the visual cortex. We then reconstruct free-viewing and structural networks and quantify their properties. Centrality measures over the entire fMRI time-series revealed a consistent functional network engaged during free-viewing that included widespread hub regions across frontal (FEF, 46v), parietal (LIP, Tpt), and occipitotemporal cortex (MT, V4 and TE) among others. Interestingly, a small number of highly-weighted and long-length inter-hemispheric connections indicated the presence of long-range integrative properties during free-viewing. We hypothesized that during free-viewing, networks had the capacity to change their local and distal connections depending on the on-going changes in visual scenes. To capture these network dynamics, we depart from the static modular architecture of the structural networks and demonstrate that hubs in free-viewing networks reorganize according to the presence of objects, motion, and faces in the movie scenes indicating poly-functional properties. Lastly, we compare each NHP subject network and observe high consistency between individuals across the same network type with closer correspondence between structural networks (e.g., diffusion based and those partially assembled from tract-tracing). In summary, our network analyses revealed ongoing changes in large-scale functional organization present during free-viewing in the macaque monkey and highlight the advantages of multi-contrast imaging in awake monkeys for investigating dynamical processes in visual cognition. To further promote the use of naturalistic free-viewing paradigms and increase the development of macaque neuroimaging resources, we share our datasets in the PRIME-DE consortium.

neuroscience↗