Neural Circuits Research Articles

Autonomous and ubiquitous in-node learning algorithms of active directed graphs and its storage behavior

The brain’s memory system is extraordinarily complex, evidenced by the multitude of neurons involved and the intricate electrochemical activities within them, as well as the complex interactions among neurons. Memory research spans various levels, from cellular and molecular to cognitive behavioral studies, each with its own focus, making it challenging to fully describe the memory mechanism. Many details of how biological neuronal networks encode, store, and retrieve information remain unknown. In this study, we model biological neuronal networks as active directed graphs, where each node is self-adaptive and relies on local information for decision-making. To explore how these networks implement memory mechanisms, we propose a parallel distributed information access algorithm based on the node scale of the active directed graph. Here, subgraphs are seen as the physical realization of the information stored in the active directed graph. Unlike traditional algorithms with global perspectives, our algorithm emphasizes global node collaboration in resource utilization through local perspectives. While it may not achieve the global optimum like a global-view algorithm, it offers superior robustness, concurrency, decentralization, and biological feasibility. We also tested network capacity, fault tolerance, and robustness, finding that the algorithm performs better in sparser network structures.

Synchronization and chimeras in asymmetrically coupled memristive Tabu learning neuron network

The coupling between neuronal oscillators plays an intriguing role in understanding the dynamics of the biological neurons present in realistic situations. Importantly, when the coupling between these neurons assumes an asymmetric nature, it can lead to profound changes in their overall behavior. In order to explore the impact of asymmetrical coupling on neuron models subjected to magnetic flux induction, we employ a coupled Tabu learning neuron model. Specifically, we illustrate the interplay between flux coupling and asymmetric electrical synapses concerning the control parameters of the proposed system using phase portraits, time series, bifurcation analysis, and Lyapunov spectrum. In particular, we show the dynamics by taking into account asymmetric interactions between neurons, from a simple network of two coupled systems to a network of nodes. Primarily, we demonstrate that two coupled systems exhibit synchronization for a fixed magnitude of control parameter with increasing coupling strength. Furthermore, we discuss the collective dynamics for the distinct network connectivity including regular, small-world and random. For all network connections, an increase in coupling strength facilitates a transition from desynchronization to synchronization via chimera state. We believe that attaining synchronization in Tabu learning neuron can act as a pivotal factor for neuron activity, contributing to the realization of such behavior in the context of numerous cognitive processes.

Applications of Near Infrared Spectroscopy and Mirror Therapy for Upper Limb Rehabilitation in Post-Stroke Patients: A Brain Plasticity Pilot Study

Objectives: The aim of this study was to identify the neural pattern activation during mirror therapy (MT) and explore any cortical reorganization and reducing asymmetry of hemispheric activity for upper limb rehabilitation in post-stroke patients. Methods: A box containing a mirror was placed between the arms of the patients to create the illusion of normal motion in the affected limb by reflecting the image of the unaffected limb in motion. We measured the cerebral hemodynamic response using near-infrared spectroscopy (NIRS). We enrolled ten right-handed stroke patients. They observed healthy hand movements in the mirror (MT condition) while performing various tasks (MT condition), and then repeated the same tasks with the mirror covered (N-MT condition). Results: Significant activation of some brain areas was observed in the right and left hemiparesis groups for the MT condition, while lower levels of activation were observed for the N-MT condition. The results showed significant differences in hemodynamic response based on oxygenated (HbO) concentrations between MT and N-MT conditions across all tasks in sensorimotor areas. These neural circuits were activated despite the motor areas being affected by the brain injury, indicating that the reflection of movement in the mirror helped to activate them. Conclusions: These results suggest that MT promotes cortical activations of sensory motor areas in affected and non-affected brain sides in subacute post-stroke patients, and it encourages the use of these tools in clinical practice.

Functional analysis of antigen presentation by enteric glial cells during intestinal inflammation.

The Enteric Nervous System is composed of a vastly interconnected network of neurons and glial cells that coordinate to regulate homeostatic gut function including intestinal motility, nutrient sensing, and mucosal barrier immunity. Enteric Glial Cells (EGCs) are a heterogeneous cell population located throughout the gastrointestinal tract and have well described roles in regulating intestinal immune responses. Enteric Glial Cells have been suggested to act as nonconventional antigen presenting cells via the Major Histocompatibility Complex II (MHC II), though this has not been confirmed functionally. Here, we investigate the capability of EGCs to present antigen on MHC I and MHC II using in vitro antigen presentation assays performed with primary murine EGC cultures. We found that EGCs are capable of functional antigen presentation on MHC I, including antigen cross-presentation, but are not capable of functional antigen presentation on MHC II. We also determined EGC cell surface MHC I and MHC II expression levels by flow cytometry during intestinal inflammation during Dextran Sodium Sulfate-induced colitis or acute Toxoplasma gondii infection. We found that EGCs upregulate MHC I during acute T. gondii infection and induce low-level MHC II expression. These findings suggest that EGCs may be important in the regulation of CD8+ T cell responses via MHC I mediated antigen (cross) presentation but may not be relevant for MHC II-mediated antigen presentation.

A historical perspective on the insect central complex: Anatomy, development, and function

The central complex (CX), a remarkable brain region at the core of insect behaviors, has been the subject of extensive research for decades. In this review, we offer a comprehensive historical perspective on the anatomy, development, and function of the CX. The CX consists of discrete and highly structured neuropils found at the center of the brain, which are conserved across insects and arthropods. The developmental processes that shape the CX are themselves conserved across insects. In early research, the CX had been shown to receive visual information and control motor function. Using increasingly advanced methods throughout the years, it has become clear that the CX is involved in high-level behavioral control, such as in vector navigation and goal directed orientation. Its numerical simplicity presents a rare opportunity to study structure-function relationships in small brains, gain insights into evolutionary neurobiology, and develop novel neuromorphic technologies inspired by insect brains. Since the CX is a highly conserved brain region involved in the control of spatial tasks, it is uniquely suited to gain a detailed understanding of the computations required for these processes at the level of neural circuits.

Adenosine-Dependent Arousal Induced by Astrocytes in a Brainstem Circuit.

Astrocytes play a crucial role in regulating sleep-wake behavior. However, how astrocytes govern a specific sleep-arousal circuit remains unknown. Here, the authors show that parafacial zone (PZ) astrocytes responded to sleep-wake cycles with state-differential Ca2+ activity, peaking during transitions from sleep to wakefulness. Using chemogenetic and optogenetic approaches, they find that activating PZ astrocytes elicited and sustained wakefulness by prolonging arousal episodes while impeding transitions from wakefulness to non-rapid eye movement (NREM) sleep. Activation of PZ astrocytes specially induced the elevation of extracellular adenosine through the ATP hydrolysis pathway but not equilibrative nucleoside transporter (ENT) mediated transportation. Strikingly, the rise in adenosine levels induced arousal by activating A1 receptors, suggesting a distinct role for adenosine in the PZ beyond its conventional sleep homeostasis modulation observed in the basal forebrain (BF) and cortex. Moreover, at the circuit level, PZ astrocyte activation induced arousal by suppressing the GABA release from the PZGABA neurons, which promote NREM sleep and project to the parabrachial nucleus (PB). Thus, their study unveils a distinctive arousal-promoting effect of astrocytes within the PZ through extracellular adenosine and elucidates the underlying mechanism at the neural circuit level.

Unleashing the Power of Induced Pluripotent stem Cells in in vitro Modelling of Lesch-Nyhan Disease.

Lesch-Nyhan disease (LND) is a monogenic rare neurodevelopmental disorder caused by a deficiency in hypoxanthine-guanine phosphoribosyltransferase (HPRT), the key enzyme of the purines salvage pathway. Beyond its well-documented metabolic consequences, HPRT deficiency leads to a distinctive neurobehavioral syndrome characterized by motor disabilities, cognitive deficits, and self-injurious behavior. Although various cell and animal models have been developed to investigate LND pathology, none have adequately elucidated the underlying mechanisms of its neurological alterations. Recent advances in human pluripotent stem cell research and in vitro differentiation techniques have ushered in a new era in rare neurodevelopmental disorders research. Pluripotent stem cells, with their ability to propagate indefinitely and to differentiate into virtually any cell type, offer a valuable alternative for modeling rare diseases, allowing for the detection of pathological events from the earliest stages of neuronal network development. Furthermore, the generation of patient-derived induced pluripotent stem cells using reprogramming technology provides an opportunity to develop a disease-relevant model within the context of a patient-specific genome. In this review, we examine current stem cell-based models of LND and assess their potential as optimal models for exploring key pathological molecular events during neurogenesis and for the discovering novel treatment options. We also address the limitations, challenges, and future prospects for improving the use of iPSCs in LND research.

Decellularized Extracellular Matrix Scaffolds: Recent Advances and Emerging Strategies in Bone Tissue Engineering.

Bone tissue engineering (BTE) is a complex biological process involving the repair of bone tissue with proper neuronal network and vasculature as well as bone surrounding soft tissue. Synthetic biomaterials used for BTE should be biocompatible, support bone tissue regeneration, and eventually be degraded in situ and replaced with the newly generated bone tissue. Recently, various forms of bone graft materials such as hydrogel, nanofiber scaffolds, and 3D printed composite scaffolds have been developed for BTE application. Decellularized extracellular matrix (DECM), a kind of natural biological material obtained from specific tissues and organs, has certain advantages over synthetic and exogenous biomaterial-derived bone grafts. Moreover, DECM can be developed from a wide range of biological sources and possesses strong molding abilities, natural 3D structures, and bioactive factors. Although DECM has shown robust osteogenic, proangiogenic, immunomodulatory, and bone defect healing potential, the rapid degradation and limited mechanical properties should be improved for bench-to-bed translation in BTE. This review summarizes the recent advances in DECM-based BTE and discusses emerging strategies of DECM-based BTE.

Synapses learn to utilize stochastic pre-synaptic release for the prediction of postsynaptic dynamics.

Synapses in the brain are highly noisy, which leads to a large trial-by-trial variability. Given how costly synapses are in terms of energy consumption these high levels of noise are surprising. Here we propose that synapses use noise to represent uncertainties about the somatic activity of the postsynaptic neuron. To show this, we developed a mathematical framework, in which the synapse as a whole interacts with the soma of the postsynaptic neuron in a similar way to an agent that is situated and behaves in an uncertain, dynamic environment. This framework suggests that synapses use an implicit internal model of the somatic membrane dynamics that is being updated by a synaptic learning rule, which resembles experimentally well-established LTP/LTD mechanisms. In addition, this approach entails that a synapse utilizes its inherently noisy synaptic release to also encode its uncertainty about the state of the somatic potential. Although each synapse strives for predicting the somatic dynamics of its postsynaptic neuron, we show that the emergent dynamics of many synapses in a neuronal network resolve different learning problems such as pattern classification or closed-loop control in a dynamic environment. Hereby, synapses coordinate themselves to represent and utilize uncertainties on the network level in behaviorally ambiguous situations.

Hippocampal contextualization of social rewards in mice

Acquiring and exploiting memories of rewarding experiences is critical for survival. The spatial environment in which a rewarding stimulus is encountered regulates memory retrieval. The ventral hippocampus (vH) has been implicated in contextual memories involving rewarding stimuli such as food, social cues or drugs. Yet, the neuronal representations and circuits underlying contextual memories of socially rewarding stimuli are poorly understood. Here, using in vivo electrophysiological recordings, in vivo one-photon calcium imaging, and optogenetics during a social reward contextual conditioning paradigm in male mice, we show that vH neurons discriminate between contexts with neutral or acquired social reward value. The formation of context-discriminating vH neurons following learning was contingent upon the presence of unconditioned stimuli. Moreover, vH neurons showed distinct contextual representations during the retrieval of social reward compared to fear contextual memories. Finally, optogenetic inhibition of locus coeruleus (LC) projections in the vH selectively disrupted social reward contextual memory by impairing vH contextual representations. Collectively, our findings reveal that the vH integrates contextual and social reward information, with memory encoding of these representations supported by input from the LC.

A Neural Circuit For Bergamot Essential Oil-Induced Anxiolytic Effects.

Aromatic essential oils have been shown to relieve anxiety and enhance relaxation, although the neural circuits underlying these effects have remained unknown. Here, it is found that treatment with 1.0% bergamot essential oil (BEO) exerts anxiolytic-like effects through a neural circuit projecting from the anterior olfactory nucleus (AON) to the anterior cingulate cortex (ACC) in acute restraint stress model mice. Collectively, in vivo two-photon calcium imaging, viral tracing, and whole-cell patch clamp recordings show that inhalation exposure to 1.0% BEO can activate glutamatergic projections from the AON to GABAergic neurons in the ACC, which drives inhibition of local glutamatergic neurons (AONGlu→ACCGABA→Glu). Optogenetic or chemogenetic manipulation of this pathway can recapitulate or abolish the BEO-induced anxiolytic-like behavioral effects in mice with ARS. Beyond depicting a previously unrecognized pathway involved in stress response, this study provides a circuit mechanism for the effects of BEO and suggests a potential target for anxiety treatment.

Existence and stability criteria for global synchrony and for synchrony in two alternating clusters of pulse-coupled oscillators updated to include conduction delays

Phase Response Curves (PRCs) have been useful in determining and analyzing various phase-locking modes in networks of oscillators under pulse-coupling assumptions, as reviewed in Mathematical Biosciences, 226:77–96, 2010. Here, we update that review to include progress since 2010 on pulse coupled oscillators with conduction delays. We then present original results that extend the derivation of the criteria for stability of global synchrony in networks of pulse-coupled oscillators to include conduction delays. We also incorporate conduction delays to extend previous studies that showed how an alternating firing pattern between two synchronized clusters could enforce within-cluster synchrony, even for clusters unable to synchronize themselves in isolation. To obtain these results, we used self-connected neurons to represent clusters. These results greatly extend the applicability of the stability analyses to networks of pulse-coupled oscillators since conduction delays are ubiquitous and strongly impact the stability of synchrony. Although these analyses only strictly apply to identical oscillators with identical connections to other oscillators, the principles are general and suggest how to promote or impede synchrony in physiological networks of neurons, for example. Heterogeneity can be interpreted as a form of frozen noise, and approximate synchrony can be sustained despite heterogeneity. The pulse-coupled oscillator model can not only be used to describe biological neuronal networks but also cardiac pacemakers, lasers, fireflies, artificial neural networks, social self-organization, and wireless sensor networks.

Astrocytes and Memory: Implications for the Treatment of Memory-related Disorders.

Memory refers to the imprint accumulated in the brain by life experiences and represents the basis for humans to engage in advanced psychological activities such as thinking and imagination. Previously, research activities focused on memory have always targeted neurons. However, in addition to neurons, astrocytes are also involved in the encoding, consolidation, and extinction of memory. In particular, astrocytes are known to affect the recruitment and function of neurons at the level of local synapses and brain networks. Moreover, the involvement of astrocytes in memory and memory-related disorders, especially in Alzheimer's disease (AD) and post-traumatic stress disorder (PTSD), has been investigated extensively. In this review, we describe the unique contributions of astrocytes to synaptic plasticity and neuronal networks and discuss the role of astrocytes in different types of memory processing. In addition, we also explore the roles of astrocytes in the pathogenesis of memory-related disorders, such as AD, brain aging, PTSD and addiction, thus suggesting that targeting astrocytes may represent a potential strategy to treat memory-related neurological diseases. In conclusion, this review emphasizes that thinking from the perspective of astrocytes will provide new ideas for the diagnosis and therapy of memory-related neurological disorders.

Inverse stochastic resonance in adaptive small-world neural networks.

Inverse stochastic resonance (ISR) is a counterintuitive phenomenon where noise reduces the oscillation frequency of an oscillator to a minimum occurring at an intermediate noise intensity, and sometimes even to the complete absence of oscillations. In neuroscience, ISR was first experimentally verified with cerebellar Purkinje neurons [Buchin et al., PLOS Comput. Biol. 12, e1005000 (2016)]. These experiments showed that ISR enables a locally optimal information transfer between the input and output spike train of neurons. Subsequent studies have further demonstrated the efficiency of information processing and transfer in neural networks with small-world network topology. We have conducted a numerical investigation into the impact of adaptivity on ISR in a small-world network of noisy FitzHugh-Nagumo (FHN) neurons, operating in a bi-metastable regime consisting of a metastable fixed point and a metastable limit cycle. Our results show that the degree of ISR is highly dependent on the value of the FHN model's timescale separation parameter ε. The network structure undergoes dynamic adaptation via mechanisms of either spike-time-dependent plasticity (STDP) with potentiation-/depression-domination parameter P or homeostatic structural plasticity (HSP) with rewiring frequency F. We demonstrate that both STDP and HSP amplify the effect of ISR when ε lies within the bi-stability region of FHN neurons. Specifically, at larger values of ε within the bi-stability regime, higher rewiring frequencies F are observed to enhance ISR at intermediate (weak) synaptic noise intensities, while values of P consistent with depression-domination (potentiation-domination) consistently enhance (deteriorate) ISR. Moreover, although STDP and HSP control parameters may jointly enhance ISR, P has a greater impact on improving ISR compared to F. Our findings inform future ISR enhancement strategies in noisy artificial neural circuits, aiming to optimize local information transfer between input and output spike trains in neuromorphic systems and prompt venues for experiments in neural networks.

A large field-of-view, single-cell-resolution two- and three-photon microscope for deep and wide imaging

In vivo imaging of large-scale neuronal activity plays a pivotal role in unraveling the function of the brain's circuitry. Multiphoton microscopy, a powerful tool for deep-tissue imaging, has received sustained interest in advancing its speed, field of view and imaging depth. However, to avoid thermal damage in scattering biological tissue, field of view decreases exponentially as imaging depth increases. We present a suite of innovations to optimize three-photon microscopy for large field-of-view imaging at depths unreachable by two-photon microscopy. These techniques enable us to image neuronal activities of transgenic animals expressing protein calcium sensors in a ~ 3.5-mm diameter field-of-view with single-cell resolution in the deepest cortical layer of mouse brains. We further demonstrate simultaneous large field-of-view two-photon and three-photon imaging, subcortical imaging in the mouse brain, and whole-brain imaging in adult zebrafish. The demonstrated techniques can be integrated into typical multiphoton microscopes to enlarge field of view for system-level neural circuit research.

Alpha-2 nicotinic acetylcholine receptors regulate spectral integration in auditory cortex

IntroductionIn primary auditory cortex (A1), nicotinic acetylcholine receptors (nAChRs) containing α2 subunits are expressed in layer 5 Martinotti cells (MCs)—inhibitory interneurons that send a main axon to superficial layers to inhibit distal apical dendrites of pyramidal cells (PCs). MCs also contact interneurons in supragranular layers that, in turn, inhibit PCs. Thus, MCs may regulate PCs via inhibition and disinhibition, respectively, of distal and proximal apical dendrites. Auditory inputs to PCs include thalamocortical inputs to middle layers relaying information about characteristic frequency (CF) and near-CF stimuli, and intracortical long-distance (“horizontal”) projections to multiple layers carrying information about spectrally distant (“nonCF”) stimuli. CF and nonCF inputs integrate to create broad frequency receptive fields (RFs). Systemic administration of nicotine activates nAChRs to “sharpen” RFs—to increase gain within a narrowed RF—resulting in enhanced responses to CF stimuli and reduced responses to nonCF stimuli. While nicotinic mechanisms to increase gain have been identified, the mechanism underlying RF narrowing is unknown.MethodsHere, we examine the role of α2 nAChRs in mice with α2 nAChR-expressing neurons labeled fluorescently, and in mice with α2 nAChRs genetically deleted.ResultsThe distribution of fluorescent neurons in auditory cortex was consistent with previous studies demonstrating α2 nAChRs in layer 5 MCs, including nonpyramidal somata in layer 5 and dense processes in layer 1. We also observed label in subcortical auditory regions, including processes, but no somata, in the medial geniculate body, and both fibers and somata in the inferior colliculus. Using electrophysiological (current-source density) recordings in α2 nAChR knock-out mice, we found that systemic nicotine failed to enhance CF-evoked inputs to layer 4, suggesting a role for subcortical α2 nAChRs, and failed to reduce nonCF-evoked responses, suggesting that α2 nAChRs regulate horizontal projections to produce RF narrowing.DiscussionThe results support the hypothesis that α2 nAChRs function to simultaneously enhance RF gain and narrow RF breadth in A1. Notably, a similar neural circuit may recur throughout cortex and hippocampus, suggesting widespread conserved functions regulated by α2 nAChRs.

Experimental West Nile virus infection provides lessons for recovery from enteric neuropathies.

Loss of enteric neurons leading to long-term gastrointestinal dysfunction is common to many diseases, and the path to functional recovery is unclear. In this issue of the JCI, Janova et al. report that West Nile virus killed enteric neurons and glia via CD4+ and CD8+ T cells acting through the perforin and Fas ligand pathways. Enteric glial cells contributed to neurogenesis and at least partial replacement of affected neurons. While neurogenesis is important for recovery, dysmotility and disruptions to the network structure persisted. Following enteric injury, the contribution of neurogenesis and the conditions that support restoration of enteric neural circuits for functional recovery remain for further investigation.

Infralimbic-basolateral amygdala circuit associated with depression-like not anxiety-like behaviors induced by chronic neuropathic pain and the antidepressant effects of electroacupuncture

Chronic pain, such as neuropathic pain, can lead to anxiety, depression, and other negative emotions, thereby forming comorbidities and increasing the risk of chronic pain over time. Both the infralimbic amygdala (IL) and the basolateral amygdala (BLA) are significantly associated with negative emotions and pain, and they are known to have reciprocal connections. However, the role of IL-BLA circuit pathways in neuropathic pain-induced anxiety and depression remains unexplored. Electroacupuncture (EA) is frequently employed in the treatment of chronic pain and emotional disorders. However, The mechanism by which EA mediates its analgesic and emotion-alleviating effects via the IL-BLA circuit remains uncertain. Here, we used chemogenetic manipulation combined with behavioral tests to detect pain induced anxiety-like and depression-like behaviors. We observed that activation of the IL-BLA circuit by chemogenetic activation induced depression-like behavior of mice. Additionally, we discovered that chemogenetic activation of the IL-BLA circuit successfully prevented the beneficial effects of EA on depression-like behavior brought on by chronic pain in mice with spared nerve injury (SNI). We discovered that SNI-induced depression-like behavior could be mitigated by inhibiting the circuit, and EA had a comparable depressive-relieving effect. Furthermore, the IL-BLA circuit's activation or inhibition had no effect on the anxiety-like feelings brought on by SNI. Overall, our findings identify a specific neural circuit that selectively regulates pain-induced depression-like emotions, without affecting pain-induced anxiety-like emotions. This discovery offers a precise target for future treatments of comorbid pain and depression and provides a plausible explanation for the efficacy of EA in treating depression-like emotions associated with chronic pain.

Efficient and Accurate Semi-Automatic Neuron Tracing with Extended Reality.

Neuron tracing, alternately referred to as neuron reconstruction, is the procedure for extracting the digital representation of the three-dimensional neuronal morphology from stacks of microscopic images. Achieving accurate neuron tracing is critical for profiling the neuroanatomical structure at single-cell level and analyzing the neuronal circuits and projections at whole-brain scale. However, the process often demands substantial human involvement and represents a nontrivial task. Conventional solutions towards neuron tracing often contend with challenges such as non-intuitive user interactions, suboptimal data generation throughput, and ambiguous visualization. In this paper, we introduce a novel method that leverages the power of extended reality (XR) for intuitive and progressive semi-automatic neuron tracing in real time. In our method, we have defined a set of interactors for controllable and efficient interactions for neuron tracing in an immersive environment. We have also developed a GPU-accelerated automatic tracing algorithm that can generate updated neuron reconstruction in real time. In addition, we have built a visualizer for fast and improved visual experience, particularly when working with both volumetric images and 3D objects. Our method has been successfully implemented with one virtual reality (VR) headset and one augmented reality (AR) headset with satisfying results achieved. We also conducted two user studies and proved the effectiveness of the interactors and the efficiency of our method in comparison with other approaches for neuron tracing.

Optogenetic Manipulation of Covert Attention in the Nonhuman Primate

Abstract Optogenetics affords new opportunities to interrogate neuronal circuits that control behavior. In primates, the usefulness of optogenetics in studying cognitive functions remains a challenge. The technique has been successfully wielded, but behavioral effects have been demonstrated primarily for sensorimotor processes. Here, we tested whether brief optogenetic suppression of primate superior colliculus can change performance in a covert attention task, in addition to previously reported optogenetic effects on saccadic eye movements. We used an attention task that required the monkey to detect and report a stimulus change at a cued location via joystick release, while ignoring changes at an uncued location. When the cued location was positioned in the response fields of transduced neurons in the superior colliculus, transient light delivery coincident with the stimulus change disrupted the monkey's detection performance, significantly lowering hit rates. When the cued location was elsewhere, hit rates were unaltered, indicating that the effect was spatially specific and not a motor deficit. Hit rates for trials with only one stimulus were also unaltered, indicating that the effect depended on selection among distractors rather than a low-level visual impairment. Psychophysical analysis revealed that optogenetic suppression increased perceptual threshold, but only for locations matching the transduced site. These data show that optogenetic manipulations can cause brief and spatially specific deficits in covert attention, independent of sensorimotor functions. This dissociation of effect, and the temporal precision provided by the technique, demonstrates the utility of optogenetics in interrogating neuronal circuits that mediate cognitive functions in the primate.