Involvement of superior colliculus in complex figure detection of mice.

Object detection is an essential function of the visual system. Although the visual cortex plays an important role in object detection, the superior colliculus can support detection when the visual cortex is ablated or silenced. Moreover, it has been shown that superficial layers of mouse SC (sSC) encode visual features of complex objects, and that this code is not inherited from the primary visual cortex. This suggests that mouse sSC may provide a significant contribution to complex object vision. Here, we use optogenetics to show that mouse sSC is involved in figure detection based on differences in figure contrast, orientation, and phase. Additionally, our neural recordings show that in mouse sSC, image elements that belong to a figure elicit stronger activity than those same elements when they are part of the background. The discriminability of this neural code is higher for correct trials than for incorrect trials. Our results provide new insight into the behavioral relevance of the visual processing that takes place in sSC.

Experience shapes chandelier cell function and structure in the visual cortex.

Detailed characterization of interneuron types in primary visual cortex (V1) has greatly contributed to understanding visual perception, yet the role of chandelier cells (ChCs) in visual processing remains poorly characterized. Using viral tracing we found that V1 ChCs predominantly receive monosynaptic input from local layer 5 pyramidal cells and higher-order cortical regions. Two-photon calcium imaging and convolutional neural network modeling revealed that ChCs are visually responsive but weakly selective for stimulus content. In mice running in a virtual tunnel, ChCs respond strongly to events known to elicit arousal, including locomotion and visuomotor mismatch. Repeated exposure of the mice to the virtual tunnel was accompanied by reduced visual responses of ChCs and structural plasticity of ChC boutons and axon initial segment length. Finally, ChCs only weakly inhibited pyramidal cells. These findings suggest that ChCs provide an arousal-related signal to layer 2/3 pyramidal cells that may modulate their activity and/or gate plasticity of their axon initial segments during behaviorally relevant events.

The representation of occluded image regions in area V1 of monkeys and humans.

Neuronal activity in the primary visual cortex (V1) is driven by feedforward input from within the neurons' receptive fields (RFs) and modulated by contextual information in regions surrounding the RF. The effect of contextual information on spiking activity occurs rapidly and is therefore challenging to dissociate from feedforward input. To address this challenge, we recorded the spiking activity of V1 neurons in monkeys viewing either natural scenes or scenes where the information in the RF was occluded, effectively removing the feedforward input. We found that V1 neurons responded rapidly and selectively to occluded scenes. V1 responses elicited by occluded stimuli could be used to decode individual scenes and could be predicted from those elicited by non-occluded images, indicating that there is an overlap between visually driven and contextual responses. We used representational similarity analysis to show that the structure of V1 representations of occluded scenes measured with electrophysiology in monkeys correlates strongly with the representations of the same scenes in humans measured with functional magnetic resonance imaging (fMRI). Our results reveal that contextual influences rapidly alter V1 spiking activity in monkeys over distances of several degrees in the visual field, carry information about individual scenes, and resemble those in human V1. VIDEO ABSTRACT.

Contextual drive of neuronal responses in mouse V1 in the absence of feedforward input.

Neurons in the primary visual cortex (V1) respond to stimuli in their receptive field (RF), which is defined by the feedforward input from the retina. However, V1 neurons are also sensitive to contextual information outside their RF, even if the RF itself is unstimulated. Here, we examined the cortical circuits for V1 contextual responses to gray disks superimposed on different backgrounds. Contextual responses began late and were strongest in the feedback-recipient layers of V1. They differed between the three main classes of inhibitory neurons, with particularly strong contextual drive of VIP neurons, indicating a contribution of disinhibitory circuits to contextual drive. Contextual drive was strongest when the gray disk was perceived as figure, occluding its background, rather than a hole. Our results link contextual drive in V1 to perceptual organization and provide previously unknown insight into how recurrent processing shapes the response of sensory neurons to facilitate figure perception.

Intracranial human recordings reveal association between neural activity and perceived intensity for the pain of others in the insula.

Based on neuroimaging data, the insula is considered important for people to empathize with the pain of others. Here, we present intracranial electroencephalographic (iEEG) recordings and single-cell recordings from the human insula while seven epilepsy patients rated the intensity of a woman's painful experiences seen in short movie clips. Pain had to be deduced from seeing facial expressions or a hand being slapped by a belt. We found activity in the broadband 20-190 Hz range correlated with the trial-by-trial perceived intensity in the insula for both types of stimuli. Within the insula, some locations had activity correlating with perceived intensity for our facial expressions but not for our hand stimuli, others only for our hand but not our face stimuli, and others for both. The timing of responses to the sight of the hand being hit is best explained by kinematic information; that for our facial expressions, by shape information. Comparing the broadband activity in the iEEG signal with spiking activity from a small number of neurons and an fMRI experiment with similar stimuli revealed a consistent spatial organization, with stronger associations with intensity more anteriorly, while viewing the hand being slapped.

Oscillations support short latency co-firing of neurons during human episodic memory formation.

Theta and gamma oscillations in the medial temporal lobe are suggested to play a critical role for human memory formation via establishing synchrony in neural assemblies. Arguably, such synchrony facilitates efficient information transfer between neurons and enhances synaptic plasticity, both of which benefit episodic memory formation. However, to date little evidence exists from humans that would provide direct evidence for such a specific role of theta and gamma oscillations for episodic memory formation. Here, we investigate how oscillations shape the temporal structure of neural firing during memory formation in the medial temporal lobe. We measured neural firing and local field potentials in human epilepsy patients via micro-wire electrode recordings to analyze whether brain oscillations are related to co-incidences of firing between neurons during successful and unsuccessful encoding of episodic memories. The results show that phase-coupling of neurons to faster theta and gamma oscillations correlates with co-firing at short latencies (~20-30 ms) and occurs during successful memory formation. Phase-coupling at slower oscillations in these same frequency bands, in contrast, correlates with longer co-firing latencies and occurs during memory failure. Thus, our findings suggest that neural oscillations play a role for the synchronization of neural firing in the medial temporal lobe during the encoding of episodic memories.

A neuronal basis of iconic memory in macaque primary visual cortex.

After a briefly presented visual stimulus disappears, observers retain a detailed representation of this stimulus for a short period of time. This sensory storage is called iconic memory. We measured iconic memory in the perception of monkeys and its neuronal correlates in the primary visual cortex (area V1). We determined how many milliseconds extra viewing time iconic memory is worth and how it decays by varying the duration of a brief stimulus and the timing of a mask. The V1 activity that persists after the disappearance of a stimulus predicted accuracy, with a time course resembling the worth and decay of iconic memory. Finally, we examined how iconic memory interacts with attention. A cue presented after the stimulus disappears boosts attentional influences pertaining to a relevant part of the stimulus but only if it appears before iconic memory decayed. Our results relate iconic memory to neuronal activity in early visual cortex.

Theta-phase dependent neuronal coding during sequence learning in human single neurons.

The ability to maintain a sequence of items in memory is a fundamental cognitive function. In the rodent hippocampus, the representation of sequentially organized spatial locations is reflected by the phase of action potentials relative to the theta oscillation (phase precession). We investigated whether the timing of neuronal activity relative to the theta brain oscillation also reflects sequence order in the medial temporal lobe of humans. We used a task in which human participants learned a fixed sequence of pictures and recorded single neuron and local field potential activity with implanted electrodes. We report that spikes for three consecutive items in the sequence (the preferred stimulus for each cell, as well as the stimuli immediately preceding and following it) were phase-locked at distinct phases of the theta oscillation. Consistent with phase precession, spikes were fired at progressively earlier phases as the sequence advanced. These findings generalize previous findings in the rodent hippocampus to the human temporal lobe and suggest that encoding stimulus information at distinct oscillatory phases may play a role in maintaining sequential order in memory.

The essential role of recurrent processing for figure-ground perception in mice.

The segregation of figures from the background is an important step in visual perception. In primary visual cortex, figures evoke stronger activity than backgrounds during a delayed phase of the neuronal responses, but it is unknown how this figure-ground modulation (FGM) arises and whether it is necessary for perception. Here, we show, using optogenetic silencing in mice, that the delayed V1 response phase is necessary for figure-ground segregation. Neurons in higher visual areas also exhibit FGM and optogenetic silencing of higher areas reduced FGM in V1. In V1, figures elicited higher activity of vasoactive intestinal peptide-expressing (VIP) interneurons than the background, whereas figures suppressed somatostatin-positive interneurons, resulting in an increased activation of pyramidal cells. Optogenetic silencing of VIP neurons reduced FGM in V1, indicating that disinhibitory circuits contribute to FGM. Our results provide insight into how lower and higher areas of the visual cortex interact to shape visual perception.

Human Hippocampal Neurons Track Moments in a Sequence of Events.

An indispensable feature of episodic memory is our ability to temporally piece together different elements of an experience into a coherent memory. Hippocampal time cells-neurons that represent temporal information-may play a critical role in this process. Although these cells have been repeatedly found in rodents, it is still unclear to what extent similar temporal selectivity exists in the human hippocampus. Here, we show that temporal context modulates the firing activity of human hippocampal neurons during structured temporal experiences. We recorded neuronal activity in the human brain while patients of either sex learned predictable sequences of pictures. We report that human time cells fire at successive moments in this task. Furthermore, time cells also signaled inherently changing temporal contexts during empty 10 s gap periods between trials while participants waited for the task to resume. Finally, population activity allowed for decoding temporal epoch identity, both during sequence learning and during the gap periods. These findings suggest that human hippocampal neurons could play an essential role in temporally organizing distinct moments of an experience in episodic memory.SIGNIFICANCE STATEMENT Episodic memory refers to our ability to remember the what, where, and when of a past experience. Representing time is an important component of this form of memory. Here, we show that neurons in the human hippocampus represent temporal information. This temporal signature was observed both when participants were actively engaged in a memory task, as well as during 10-s-long gaps when they were asked to wait before performing the task. Furthermore, the activity of the population of hippocampal cells allowed for decoding one temporal epoch from another. These results suggest a robust representation of time in the human hippocampus.

Mouse visual cortex contains a region of enhanced spatial resolution.

The representation of space in mouse visual cortex was thought to be relatively uniform. Here we reveal, using population receptive-field (pRF) mapping techniques, that mouse visual cortex contains a region in which pRFs are considerably smaller. This region, the "focea," represents a location in space in front of, and slightly above, the mouse. Using two-photon imaging we show that the smaller pRFs are due to lower scatter of receptive-fields at the focea and an over-representation of binocular regions of space. We show that receptive-fields of single-neurons in areas LM and AL are smaller at the focea and that mice have improved visual resolution in this region of space. Furthermore, freely moving mice make compensatory eye-movements to hold this region in front of them. Our results indicate that mice have spatial biases in their visual processing, a finding that has important implications for the use of the mouse model of vision.

A Quantitative Comparison of Inhibitory Interneuron Size and Distribution between Mouse and Macaque V1, Using Calcium-Binding Proteins.

The mouse is a useful and popular model for studying of visual cortical function. To facilitate the translation of results from mice to primates, it is important to establish the extent of cortical organization equivalence between species and to identify possible differences. We focused on the different types of interneurons as defined by calcium-binding protein (CBP) expression in the layers of primary visual cortex (V1) in mouse and rhesus macaque. CBPs parvalbumin (PV), calbindin (CB), and calretinin (CR) provide a standard, largely nonoverlapping, labeling scheme in macaque, with preserved corresponding morphologies in mouse, despite a slightly higher overlap. Other protein markers, which are relevant in mouse, are not preserved in macaque. We fluorescently tagged CBPs in V1 of both species, using antibodies raised against preserved aminoacid sequences. Our data demonstrate important similarities between the expression patterns of interneuron classes in the different layers between rodents and primates. However, in macaque, expression of PV and CB is more abundant, CR expression is lower, and the laminar distribution of interneuron populations is more differentiated. Our results reveal an integrated view of interneuron types that provides a basis for translating results from rodents to primates, and suggest a reconciliation of previous results.

Activity in Lateral Visual Areas Contributes to Surround Suppression in Awake Mouse V1.

Neuronal response to sensory stimuli depends on the context. The response in primary visual cortex (V1), for instance, is reduced when a stimulus is surrounded by a similar stimulus [1-3]. The source of this surround suppression is partially known. In mouse, local horizontal integration by somatostatin-expressing interneurons contributes to surround suppression [4]. In primates, however, surround suppression arises too quickly to come from local horizontal integration alone, and myelinated axons from higher visual areas, where cells have larger receptive fields, are thought to provide additional surround suppression [5, 6]. Silencing higher visual areas indeed decreased surround suppression in the awake primate by increasing responses to large stimuli [7, 8], although not under anesthesia [9, 10]. In smaller mammals, like mice, fast surround suppression could be possible without feedback. Recent studies revealed a small reduction in V1 responses when silencing higher areas [11, 12] but have not investigated surround suppression. To determine whether higher visual areas contribute to V1 surround suppression, even when this is not necessary for fast processing, we inhibited the areas lateral to V1, particularly the lateromedial area (LM), a possible homolog of primate V2 [13], while recording in V1 of awake and anesthetized mice. We found that part of the surround suppression depends on activity from lateral visual areas in the awake, but not anesthetized, mouse. Inhibiting the lateral visual areas specifically increased responses in V1 to large stimuli. We present a model explaining how excitatory feedback to V1 can have these suppressive effects for large stimuli.

Neuroscience: Figured Out by Feedback to the Thalamus.

The lateral geniculate nucleus of the thalamus (LGN) is a relay nucleus between the retina and the visual cortex. A new brain imaging study shows that LGN activity is modulated by figure-ground organization, even when the figure and ground are presented to different eyes: a hallmark of a cortical feedback effect.

The Segmentation of Proto-Objects in the Monkey Primary Visual Cortex.

During visual perception, the brain enhances the representations of image regions that belong to figures and suppresses those that belong to the background. Natural images contain many regions that initially appear to be part of a figure when analyzed locally (proto-objects) but are actually part of the background if the whole image is considered. These proto-grounds must be correctly assigned to the background to allow correct shape identification and guide behavior. To understand how the brain resolves this conflict between local and global processing, we recorded neuronal activity from the primary visual cortex (V1) of macaque monkeys while they discriminated between n/u shapes that have a central proto-ground region. We studied the fine-grained spatiotemporal profile of neural activity evoked by the n/u shape and found that neural representation of the object proceeded from a coarse-to-fine resolution. Approximately 100 ms after the stimulus onset, the representation of the proto-ground region was enhanced together with the rest of the n/u surface, but after ∼115 ms, the proto-ground was suppressed back to the level of the background. Suppression of the proto-ground was only present in animals that had been trained to perform the shape-discrimination task, and it predicted the choice of the animal on a trial-by-trial basis. Attention enhanced figure-ground modulation, but it had no effect on the strength of proto-ground suppression. The results indicate that the accuracy of scene segmentation is sharpened by a suppressive process that resolves local ambiguities by assigning proto-grounds to the background.

Benchmarking laminar fMRI: Neuronal spiking and synaptic activity during top-down and bottom-up processing in the different layers of cortex.

High resolution laminar fMRI is beginning to probe responses in the different layers of cortex. What can we expect this exciting new technique to discover about cortical processing and how can we verify that it is producing an accurate picture of the underlying laminar differences in neural processing? This review will address our knowledge of laminar cortical circuitry gained from electrophysiological studies in macaque monkeys with a focus on the primary visual cortex, as this area has been most often targeted in both laminar electrophysiological and fMRI studies. We will review how recent studies are attempting to verify the accuracy of laminar fMRI by recreating the known laminar profiles of various neural tuning properties. Furthermore, we will examine how feedforward and feedback-related neural processes engage different cortical layers, producing canonical patterns of spiking and synaptic activity as estimated by the analysis of current-source density. These results provide a benchmark for recent studies aiming to examine the profiles of bottom-up and top-down processes with laminar fMRI. Finally, we will highlight particularly useful paradigms and approaches which may help us to understand processing in the different layers of the human cerebral cortex.

Figure-ground perception in the awake mouse and neuronal activity elicited by figure-ground stimuli in primary visual cortex.

Figure-ground segregation is the process by which the visual system identifies image elements of figures and segregates them from the background. Previous studies examined figure-ground segregation in the visual cortex of monkeys where figures elicit stronger neuronal responses than backgrounds. It was demonstrated in anesthetized mice that neurons in the primary visual cortex (V1) of mice are sensitive to orientation contrast, but it is unknown whether mice can perceptually segregate figures from a background. Here, we examined figure-ground perception of mice and found that mice can detect figures defined by an orientation that differs from the background while the figure size, position or phase varied. Electrophysiological recordings in V1 of awake mice revealed that the responses elicited by figures were stronger than those elicited by the background and even stronger at the edge between figure and background. A figural response could even be evoked in the absence of a stimulus in the V1 receptive field. Current-source-density analysis suggested that the extra activity was caused by synaptic inputs into layer 2/3. We conclude that the neuronal mechanisms of figure-ground segregation in mice are similar to those in primates, enabling investigation with the powerful techniques for circuit analysis now available in mice.

The influence of attention and reward on the learning of stimulus-response associations.

We can learn new tasks by listening to a teacher, but we can also learn by trial-and-error. Here, we investigate the factors that determine how participants learn new stimulus-response mappings by trial-and-error. Does learning in human observers comply with reinforcement learning theories, which describe how subjects learn from rewards and punishments? If yes, what is the influence of selective attention in the learning process? We developed a novel redundant-relevant learning paradigm to examine the conjoint influence of attention and reward feedback. We found that subjects only learned stimulus-response mappings for attended shapes, even when unattended shapes were equally informative. Reward magnitude also influenced learning, an effect that was stronger for attended than for non-attended shapes and that carried over to a subsequent visual search task. Our results provide insights into how attention and reward jointly determine how we learn. They support the powerful learning rules that capitalize on the conjoint influence of these two factors on neuronal plasticity.

Interocularly merged face percepts eliminate binocular rivalry.

Faces are important visual objects for humans and other social animals. A complex network of specialized brain areas is involved in the recognition and interpretation of faces. This network needs to strike a balance between being sensitive enough to distinguish between different faces with similar features, and being tolerant of low-level visual changes so that a given face is stably perceived as a particular individual. Such stability may require feedback from higher brain regions down to the level where details are represented. Here, we describe a phenomenon in which interocular competition between face features is stabilized and eliminated when observers attend high-level face characteristics. Two different face images presented to the individual eyes do not cause the perceptual fluctuations that are typically observed in binocular rivalry. Instead, they merge into a stable percept of an intermediate face that combines features from both eyes' images. The stability of the intermediate face percept depends on the observer attending holistic face properties such as identity or gender. It disappears when observers explicitly attend facial features, suggesting a crucial role of top-down stabilizing feedback from high-level areas that represent holistic faces back to lower processing levels where detailed face features compete for conscious representation.