Biology subjects

Angelucci, A.

Publications and source records attributed to Angelucci, A..

11 recordsLinked to original sources

bioRxiv2025

Laminar-specific control of response gain and orientation-tuning byparvalbumin-expressing inhibitory interneurons in primate visual cortex

Understanding the role of the different types of inhibitory interneurons in cortical computations is central to elucidating how the neocortex processes sensory information. The emergence of orientation tuning in primate primary visual cortex (V1) is a canonical model for studying how cortical sensory circuits and inhibitory interneurons compute relevant stimulus features. The selective feedforward convergence of non-orientation-selective thalamic afferents establishes initial orientation tuning in the granular V1 input layer. As signals propagate through the cortical microcircuit, orientation tuning sharpens in extra-granular layers, yet the underlying mechanisms and the contribution of specific inhibitory neuron subtypes within V1 remain unresolved. To study the role of the largest cortical inhibitory neuron subclass, parvalbumin-expressing (PV+) interneurons, in this V1 computation, we combined laminar extracellular recordings with bidirectional optogenetic manipulations of PV+ cells in marmoset V1. Our results reveal a striking laminar specificity: in granular layers, PV+ cells implement divisive/ multiplicative linear gain control, whereas in extra-granular layers they exert tuned nonlinear suppression that enhances orientation tuning. Computational modeling suggests that PV+ neurons can control gain by changing a neurons spiking threshold, and orientation tuning by changing a neurons input noise, which regulates the neurons input-output function. Our findings reconcile divergent results from previous rodent studies and establish a framework for understanding layer-dependent inhibitory computations in the primate cortex.

neuroscience↗

bioRxiv2025

Cortical Response to Acute Implantation of the Utah Optrode Array in Macaque Cortex

Optogenetics has transformed the study of neural circuit function, but limitations in its application to species with large brains, such as non-human primates (NHPs), remain. A major challenge in NHP optogenetics is delivering light to sufficiently large volumes of deep neural tissue with high spatiotemporal precision, without simultaneously affecting superficial tissue. To overcome these limitations, we recently developed and tested in vivo in NHP cortex, the Utah Optrode Array (UOA). This is a 10x10 array of penetrating glass shanks, tiling a 4x4mm2 area, bonded to interleaved needle-aligned and interstitial {micro}LED arrays, which allows for independent photostimulation of deep and superficial brain tissue. Here, we investigate the acute biological response to UOA implantation in NHP cortex, with the goal of optimizing device design for reduced insertion trauma and subsequent chronic response. To this goal, we systematically vary UOA shank diameter, surface texture, tip geometry, and insertion pressure, and assess their effects on astrocytes, microglia, and neuronal viability, following acute implantation. We find that UOAs with shanks of smaller diameter, smooth surface texture and round tips cause the least damage. Higher insertion pressures have limited effects on the inflammatory response, but lead to greater tissue compression. Our results highlight the importance of balancing shank diameter, tip geometry, and insertion pressure in UOA design for preserving tissue integrity and improving long-term UOA performance and biocompatibility.

bioengineering↗

bioRxiv2024

Primate V2 Receptive Fields Derived from Anatomically Identified Large-Scale V1 Inputs

In the primate visual system, visual object recognition involves a series of cortical areas arranged hierarchically along the ventral visual pathway. As information flows through this hierarchy, neurons become progressively tuned to more complex image features. The circuit mechanisms and computations underlying the increasing complexity of these receptive fields (RFs) remain unidentified. To understand how this complexity emerges in the secondary visual area (V2), we investigated the functional organization of inputs from the primary visual cortex (V1) to V2 by combining retrograde anatomical tracing of these inputs with functional imaging of feature maps in macaque monkey V1 and V2. We found that V1 neurons sending inputs to single V2 orientation columns have a broad range of preferred orientations, but are strongly biased towards the orientation represented at the injected V2 site. For each V2 site, we then constructed a feedforward model based on the linear combination of its anatomically-identified large-scale V1 inputs, and studied the response proprieties of the generated V2 RFs. We found that V2 RFs derived from the linear feedforward model were either elongated versions of V1 filters or had spatially complex structures. These modeled RFs predicted V2 neuron responses to oriented grating stimuli with high accuracy. Remarkably, this simple model also explained the greater selectivity to naturalistic textures of V2 cells compared to their V1 input cells. Our results demonstrate that simple linear combinations of feedforward inputs can account for the orientation selectivity and texture sensitivity of V2 RFs.

neuroscience↗

bioRxiv2024

In vivo optogenetics using a Utah Optrode Array with enhanced light output and spatial selectivity

Optogenetics allows manipulation of neural circuits in vivo with high spatial and temporal precision. However, combining this precision with control over a significant portion of the brain is technologically challenging (especially in larger animal models). Here, we have developed, optimised, and tested in vivo, the Utah Optrode Array (UOA), an electrically addressable array of optical needles and interstitial sites illuminated by 181 {micro}LEDs and used to optogenetically stimulate the brain. The device is specifically designed for non-human primate studies. Thinning the combined {micro}LED and needle backplane of the device from 300 {micro}m to 230 {micro}m improved the efficiency of light delivery to tissue by 80%, allowing lower {micro}LED drive currents, which improved power management and thermal performance. The spatial selectivity of each site was also improved by integrating an optical interposer to reduce stray light emission. These improvements were achieved using an innovative fabrication method to create an anodically bonded glass/silicon substrate with through-silicon vias etched, forming an optical interposer. Optical modelling was used to demonstrate that the tip structure of the device had a major influence on the illumination pattern. The thermal performance was evaluated through a combination of modelling and experiment, in order to ensure that cortical tissue temperatures did not rise by more than 1{degrees}C. The device was tested in vivo in the visual cortex of macaque expressing ChR2-tdTomato in cortical neurons. It was shown that the strongest optogenetic response occurred in the region surrounding the needle tips, and that the extent of the optogenetic response matched the predicted illumination profile based on optical modelling - demonstrating the improved spatial selectivity resulting from the optical interposer approach. Furthermore, different needle illumination sites generated different patterns of low-frequency potential (LFP) activity.

neuroscience↗

bioRxiv2024

Laminar specificity and coverage of viral-mediated gene expression restricted to GABAergic interneurons and their parvalbumin subclass in marmoset primary visual cortex

In the mammalian neocortex, inhibition is important for dynamically balancing excitation and shaping the response properties of cells and circuits. The various computational functions of inhibition are thought to be mediated by different inhibitory neuron types of which a large diversity exists in several species. Current understanding of the function and connectivity of distinct inhibitory neuron types has mainly derived from studies in transgenic mice. However, it is unknown whether knowledge gained from mouse studies applies to the non-human primate, the model system closest to humans. The lack of viral tools to selectively access inhibitory neuron types has been a major impediment to studying their function in the primate. Here, we have thoroughly validated and characterized several recently-developed viral vectors designed to restrict transgene expression to GABAergic cells or their parvalbumin (PV) subtype, and identified two types that show high specificity and efficiency in marmoset V1. We show that in marmoset V1 AAV-h56D induces transgene expression in GABAergic cells with up to 91-94% specificity and 79% efficiency, but this depends on viral serotype and cortical layer. AAV-PHP.eB-S5E2 induces transgene expression in PV cells across all cortical layers with up to 98% specificity and 86-90% efficiency, depending on layer. Thus, these viral vectors are promising tools for studying GABA and PV cell function and connectivity in the primate cortex.

neuroscience↗

bioRxiv2023

Size tuning of neural response variability in laminar circuits of macaque primary visual cortex

Surround suppression and neural response variability are two widespread cortical phenomena thought to facilitate and impede, respectively, information processing and perception. Typically, manipulations that elicit neural response suppression quench variability, an observation that has led some to suggest that these two phenomena may share a common origin. However, few studies have systematically examined the relationship between surround suppression and variability. Surround suppression is mediated by multiple circuits and mechanisms that depend on the size of the sensory stimulus, and cortical layer. Variability is also laminar dependent. To understand how surround suppression and variability may influence laminar processing, here we have used electrophysiological laminar recordings to examine how neural response variability and the shared variability among neurons are modulated by visual stimulus size across the layers of macaque primary visual cortex (V1). We find that surround suppression does not always quench variability. Instead, variability is tuned for stimulus size in a layer-dependent manner. In all layers, stimulation of the receptive field (RF) reduced neural response variability, and the shared variability among neurons, relative to their pre-stimulus values. As the stimulus was enlarged beyond the RF, to involve the near RF-surround, both neural response variability and shared variability further decreased in infragranular layers, but did not change in granular and supragranular layers. In contrast, larger stimuli involving the far RF-surround increased both neural response variability and shared variability, relative to their value for a stimulus matched to the RF size, in supragranular layers, but decreased them or did not change them in granular and infragranular layers. Surprisingly, we also found that visual stimuli smaller than the RF could increase variability relative to baseline values, particularly in granular and infragranular layers. Our results point to multiple laminar-specific circuits and mechanisms as the source of variability, and call for new models of neural response variability.

neuroscience↗

bioRxiv2022

An Optrode Array for Spatiotemporally Precise Large-Scale Optogenetic Stimulation of Deep Cortical Layers in Non-human Primates

Optogenetics has transformed studies of neural circuit function, but remains challenging to apply in large brains, such as those of non-human primates (NHPs). A major challenge is delivering intense, spatiotemporally precise, patterned photostimulation across large volumes in deep tissue. Such stimulation is critical, for example, to modulate selectively deep-layer corticocortical feedback projections. To address this unmet need, we have developed the Utah Optrode Array (UOA), a 10x10 glass needle waveguide array fabricated atop a novel opaque optical interposer then bonded to an electrically addressable LED array. In vivo experiments with the UOA demonstrated large-scale, spatiotemporally precise, activation of deep circuits in monkey cortex. Specifically, the UOA permitted both focal (confined to single layers/columns), and widespread (multiple layers/columns) optogenetic activation of deep layer neurons, simply by varying the number of activated LEDs and/or the irradiance. Thus, the UOA represents a powerful optoelectronic device for targeted manipulation of deep-layer circuits in NHP models.

neuroscience↗

bioRxiv2020

A direct interareal feedback-to-feedforward circuit in primate visual cortex

The mammalian sensory neocortex consists of hierarchically organized areas reciprocally connected via feedforward (FF) and feedback (FB) circuits. Several theories of hierarchical computation ascribe the bulk of the computational work of the cortex to looped FF-FB circuits between pairs of cortical areas. However, whether such corticocortical loops exist remains unclear. In higher mammals, individual FF-projection neurons send afferents almost exclusively to a single higher-level area. However, it is unclear whether FB-projection neurons show similar area specificity, and whether they influence FF-projection neurons directly or indirectly. Using viral-mediated monosynaptic circuit tracing in macaque primary visual cortex (V1), we show that V1 neurons sending FF projections to area V2 receive monosynaptic FB inputs from V2, but not other V1-projecting areas. We also find monosynaptic FB-to-FB neuron contacts as a second motif of FB connectivity. Our results support the existence of FF-FB loops in primate cortex, and suggest that FB can rapidly and selectively influence the activity of incoming FF signals.

neuroscience↗

bioRxiv2020

Stream-Specific Feedback Inputs to the Primate Primary Visual Cortex

The sensory neocortex consists of hierarchically-organized areas reciprocally connected via feedforward and feedback circuits. Feedforward connections shape the receptive field properties of neurons in higher areas within parallel streams specialized in processing specific stimulus attributes. Feedback connections, instead, have been implicated in top-down modulations, such as attention, prediction and sensory context. However, their computational role remains unknown, partly because we lack knowledge about rules of feedback connectivity to constrain models of feedback function. For example, it is unknown whether feedback connections maintain stream-specific segregation, or integrate information across parallel streams. Using selective viral-mediated labeling of feedback connections arising from specific cytochrome-oxidase stripes of macaque visual area V2, we find that feedback to the primary visual cortex (V1) is organized into parallel streams resembling the reciprocal feedforward pathways. These results suggest that functionally-specialized V2 feedback channels modulate V1 responses to specific stimulus attributes, an organizational principle that could extend to feedback pathways in other sensory systems.

neuroscience↗

bioRxiv2017

Distinct Laminar Processing of Local and Global Context in Primate Primary Visual Cortex

Visual perception is profoundly affected by spatial context. In visual cortex, neuronal responses to stimuli inside their receptive field (RF) are suppressed by contextual stimuli in the RF surround (surround suppression). How do neuronal RFs integrate information across visual space, and what role do different cortical layers play in the processing of spatial context? By recording simultaneously across all layers of macaque primary visual cortex, while presenting visual stimuli at increasing distances from the recorded cells RF, we find that near vs. far stimuli activate distinct layers. Stimuli in the near-surround evoke the earliest subthreshold responses in superficial and deep layers, and cause the earliest surround suppression of spiking responses in superficial layers. Instead, far-surround stimuli evoke the earliest subthreshold responses in feedback-recipient layers, i.e. 1 and the lower half of the deep layers, and suppress visually-evoked spiking responses almost simultaneously in all layers, except 4C, where suppression emerges latest. Our results reveal unique contributions of the cortical layers to the processing of local and global spatial context, and suggest distinct underlying circuits for local and global signal integration.

neuroscience↗

bioRxiv2016

CORTICO-CORTICAL FEEDBACK CONTROLS SPATIAL SUMMATION IN PRIMATE VISUAL CORTEX

In the cerebral cortex, sensory information travels along feedforward connections through a hierarchy of areas, which, in turn, send a denser network of feedback connections to lower-order areas. Feedback has been implicated in attention, expectation, and sensory context, but the cellular mechanisms underlying these diverse feedback functions are unknown. Using specific optogenetic inactivation of feedback connections in the primate visual cortex, we have identified the cellular mechanisms of feedback-mediated modulations of early sensory processing. Specifically, we found that feedback modulates receptive field size, surround suppression and response gain, similar to the modulatory effects of visual spatial attention. A recurrent network model captured these effects. These feedback-mediated modulations allow higher-order cortical areas to dynamically regulate spatial resolution, sensitivity to image features, and efficiency of coding natural images in lower-order cortical areas.

neuroscience↗