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 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.

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.

Mitochondrial Dynamics in Visual Cortex Are Limited In Vivo and Not Affected by Axonal Structural Plasticity.

Mitochondria buffer intracellular Ca2+ and provide energy [1]. Because synaptic structures with high Ca2+ buffering [2-4] or energy demand [5] are often localized far away from the soma, mitochondria are actively transported to these sites [6-11]. Also, the removal and degradation of mitochondria are tightly regulated [9, 12, 13], because dysfunctional mitochondria are a source of reactive oxygen species, which can damage the cell [14]. Deficits in mitochondrial trafficking have been proposed to contribute to the pathogenesis of Parkinson's disease, schizophrenia, amyotrophic lateral sclerosis, optic atrophy, and Alzheimer's disease [13, 15-19]. In neuronal cultures, about a third of mitochondria are motile, whereas the majority remains stationary for several days [8, 20]. Activity-dependent mechanisms cause mitochondria to stop at synaptic sites [7, 8, 20, 21], which affects synapse function and maintenance. Reducing mitochondrial content in dendrites decreases spine density [22, 23], whereas increasing mitochondrial content or activity increases it [7]. These bidirectional interactions between synaptic activity and mitochondrial trafficking suggest that mitochondria may regulate synaptic plasticity. Here we investigated the dynamics of mitochondria in relation to axonal boutons of neocortical pyramidal neurons for the first time in vivo. We find that under these circumstances practically all mitochondria are stationary, both during development and in adulthood. In adult visual cortex, mitochondria are preferentially localized at putative boutons, where they remain for several days. Retinal-lesion-induced cortical plasticity increases turnover of putative boutons but leaves mitochondrial turnover unaffected. We conclude that in visual cortex in vivo, mitochondria are less dynamic than in vitro, and that structural plasticity does not affect mitochondrial dynamics.

Learning a New Selection Rule in Visual and Frontal Cortex.

How do you make a decision if you do not know the rules of the game? Models of sensory decision-making suggest that choices are slow if evidence is weak, but they may only apply if the subject knows the task rules. Here, we asked how the learning of a new rule influences neuronal activity in the visual (area V1) and frontal cortex (area FEF) of monkeys. We devised a new icon-selection task. On each day, the monkeys saw 2 new icons (small pictures) and learned which one was relevant. We rewarded eye movements to a saccade target connected to the relevant icon with a curve. Neurons in visual and frontal cortex coded the monkey's choice, because the representation of the selected curve was enhanced. Learning delayed the neuronal selection signals and we uncovered the cause of this delay in V1, where learning to select the relevant icon caused an early suppression of surrounding image elements. These results demonstrate that the learning of a new rule causes a transition from fast and random decisions to a more considerate strategy that takes additional time and they reveal the contribution of visual and frontal cortex to the learning process.

Alpha and gamma oscillations characterize feedback and feedforward processing in monkey visual cortex.

Cognitive functions rely on the coordinated activity of neurons in many brain regions, but the interactions between cortical areas are not yet well understood. Here we investigated whether low-frequency (α) and high-frequency (γ) oscillations characterize different directions of information flow in monkey visual cortex. We recorded from all layers of the primary visual cortex (V1) and found that γ-waves are initiated in input layer 4 and propagate to the deep and superficial layers of cortex, whereas α-waves propagate in the opposite direction. Simultaneous recordings from V1 and downstream area V4 confirmed that γ- and α-waves propagate in the feedforward and feedback direction, respectively. Microstimulation in V1 elicited γ-oscillations in V4, whereas microstimulation in V4 elicited α-oscillations in V1, thus providing causal evidence for the opposite propagation of these rhythms. Furthermore, blocking NMDA receptors, thought to be involved in feedback processing, suppressed α while boosting γ. These results provide new insights into the relation between brain rhythms and cognition.

A unified selection signal for attention and reward in primary visual cortex.

Stimuli associated with high rewards evoke stronger neuronal activity than stimuli associated with lower rewards in many brain regions. It is not well understood how these reward effects influence activity in sensory cortices that represent low-level stimulus features. Here, we investigated the effects of reward information in the primary visual cortex (area V1) of monkeys. We found that the reward value of a stimulus relative to the value of other stimuli is a good predictor of V1 activity. Relative value biases the competition between stimuli, just as has been shown for selective attention. The neuronal latency of this reward value effect in V1 was similar to the latency of attentional influences. Moreover, V1 neurons with a strong value effect also exhibited a strong attention effect, which implies that relative value and top-down attention engage overlapping, if not identical, neuronal selection mechanisms. Our findings demonstrate that the effects of reward value reach down to the earliest sensory processing levels of the cerebral cortex and imply that theories about the effects of reward coding and top-down attention on visual representations should be unified.

No phylogeny without ontogeny: a comparative and developmental search for the sources of sleep-like neural and behavioral rhythms.

A comprehensive review is presented of reported aspects and putative mechanisms of sleep-like motility rhythms throughout the animal kingdom. It is proposed that 'rapid eye movement (REM) sleep' be regarded as a special case of a distinct but much broader category of behavior, 'rapid body movement (RBM) sleep', defined by intrinsically-generated and apparently non-purposive movements. Such a classification completes a 2 × 2 matrix defined by the axes sleep versus waking and active versus quiet. Although 'paradoxical' arousal of forebrain electrical activity is restricted to warm-blooded vertebrates, we urge that juvenile or even infantile stages of development be investigated in cold-blooded animals, in view of the many reports of REM-like spontaneous motility (RBMs) in a wide range of species during sleep. The neurophysiological bases for motorically active sleep at the brainstem level and for slow-wave sleep in the forebrain appear to be remarkably similar, and to be subserved in both cases by a primitive diffuse mode of neuronal organization. Thus, the spontaneous synchronous burst discharges which are characteristics of the sleeping brain can be readily simulated even by highly unstructured neural network models. Neuromotor discharges during active sleep appear to reflect a hierarchy of simple relaxation oscillation mechanisms, spanning a wide range of spike-dependent relaxation times, whereas the periodic alternation of active and quiet sleep states more likely results from the entrainment of intrinsic cellular rhythms and/or from activity-dependent homeostatic changes in network excitability.

Synchrony dynamics in monkey V1 predict success in visual detection.

Behavioral measures such as expectancy and attention have been associated with the strength of synchronous neural activity. On this basis, it is hypothesized that synchronous activity affects our ability to detect and recognize visual objects. To investigate the role of synchronous activity in visual perception, we studied the magnitude and precision of correlated activity, before and after stimulus presentation within the visual cortex (V1), in relation to a monkey's performance in a figure-ground discrimination task. We show that during the period of stimulus presentation a transition in synchronized activity occurs that is characterized by a reduction of the correlation peak height and width. Before stimulus onset, broad peak correlations are observed that change towards thin peak correlations after stimulus onset, due to a specific decrease of low-frequency components. The magnitude of the transition in correlated activity is larger, i.e. a stronger desynchronization occurs, when the animal perceives the stimulus correctly than when the animal fails to detect the stimulus. These results therefore show that a transition in synchronous firing is important for the detection of sensory stimuli. We hypothesize that the transition in synchrony reflects a change from loose and global neuronal interactions towards a finer temporal and spatial scale of neuronal interactions, and that such a change in neuronal interactions is required for figure-ground discrimination.

Neural responses in cat visual cortex reflect state changes in correlated activity.

Cortical state is characterized by ongoing rhythmic neural activity. Changes in rhythmic activity and thus in cortical state are shown to occur spontaneously in the anesthetized cat. We were interested in whether these state changes have an affect on the cortical processing of sensory stimuli. This was investigated by recording spontaneous and stimulus-evoked local field potentials and multi-unit neuronal activity (MUA) from trans-cortical electrode arrays in the visual cortex of the anesthetized cat. Changes in cortical state were identified by calculating the cross-correlation strength and cross-coherency, between MUA channels at different layers and on separate electrode arrays. Spontaneous changes in rhythmic activity were associated with changes in the strength of stimulus-evoked multiple unit responses of cortical neurons. The highest multi-unit responses were found in periods when low-frequency rhythms of the electroencephalogram increase in magnitude and high-frequency rhythms decrease. Such changes in evoked responses were maximal at layer IV, the input layer of the visual cortex. Our findings suggest that stimulus response magnitude depends on rhythmic state and reflects changes in functional connectivity within the visual cortex.

Correspondence of presaccadic activity in the monkey primary visual cortex with saccadic eye movements.

We continuously scan the visual world via rapid or saccadic eye movements. Such eye movements are guided by visual information, and thus the oculomotor structures that determine when and where to look need visual information to control the eye movements. To know whether visual areas contain activity that may contribute to the control of eye movements, we recorded neural responses in the visual cortex of monkeys engaged in a delayed figure-ground detection task and analyzed the activity during the period of oculomotor preparation. We show that approximately 100 ms before the onset of visually and memory-guided saccades neural activity in V1 becomes stronger where the strongest presaccadic responses are found at the location of the saccade target. In addition, in memory-guided saccades the strength of presaccadic activity shows a correlation with the onset of the saccade. These findings indicate that the primary visual cortex contains saccade-related responses and participates in visually guided oculomotor behavior.

Internal state of monkey primary visual cortex (V1) predicts figure-ground perception.

When stimulus information enters the visual cortex, it is rapidly processed for identification. However, sometimes the processing of the stimulus is inadequate and the subject fails to notice the stimulus. Human psychophysical studies show that this occurs during states of inattention or absent-mindedness. At a neurophysiological level, it remains unclear what these states are. To study the role of cortical state in perception, we analyzed neural activity in the monkey primary visual cortex before the appearance of a stimulus. We show that, before the appearance of a reported stimulus, neural activity was stronger and more correlated than for a not-reported stimulus. This indicates that the strength of neural activity and the functional connectivity between neurons in the primary visual cortex participate in the perceptual processing of stimulus information. Thus, to detect a stimulus, the visual cortex needs to be in an appropriate state.