Distinct recruitment of feedforward and recurrent pathways across higher-order areas of mouse visual cortex.

Cortical visual processing transforms features of the external world into increasingly complex and specialized neuronal representations. These transformations arise in part through target-specific routing of information; however, within-area computations may also contribute to area-specific function. Here, we sought to determine whether higher order visual cortical areas lateromedial (LM), anterolateral (AL), posteromedial (PM), and anteromedial (AM) have specialized anatomical and physiological properties by using a combination of whole-cell recordings and optogenetic stimulation of primary visual cortex (V1) axons in vitro. We discovered area-specific differences in the strength of recruitment of interneurons through feedforward and recurrent pathways, as well as differences in cell-intrinsic properties and interneuron densities. These differences were most striking when comparing across medial and lateral areas, suggesting that these areas have distinct profiles for net excitability and integration of V1 inputs. Thus, cortical areas are not defined simply by the information they receive but also by area-specific circuit properties that enable specialized filtering of these inputs.

High-fidelity optical excitation of cortico-cortical projections at physiological frequencies.

Optogenetic activation of axons is a powerful approach for determining the synaptic properties and impact of long-range projections both in vivo and in vitro. However, because of the difficulty of measuring activity in axons, our knowledge of the reliability of optogenetic axonal stimulation has relied on data from somatic recordings. Yet, there are many reasons why activation of axons may not be comparable to cell bodies. Thus we have developed an approach to more directly assess the fidelity of optogenetic activation of axonal projections. We expressed opsins (ChR2, Chronos, or oChIEF) in the mouse primary visual cortex (V1) and recorded extracellular, pharmacologically isolated presynaptic action potentials in response to axonal activation in the higher visual areas. Repetitive stimulation of axons with ChR2 resulted in a 70% reduction in the fiber volley amplitude and a 60% increase in the latency at all frequencies tested (10-40 Hz). Thus ChR2 cannot reliably recruit axons during repetitive stimulation, even at frequencies that are reliable for somatic stimulation, likely due to pronounced channel inactivation at the high light powers required to evoke action potentials. By comparison, oChIEF and Chronos evoked photocurrents that inactivated minimally and could produce reliable axon stimulation at frequencies up to 60 Hz. Our approach provides a more direct and accurate evaluation of the efficacy of new optogenetic tools and has identified Chronos and oChIEF as viable tools to interrogate the synaptic and circuit function of long-range projections.

Chromatic detection from cone photoreceptors to V1 neurons to behavior in rhesus monkeys.

Chromatic sensitivity cannot exceed limits set by noise in the cone photoreceptors. To determine how close neurophysiological and psychophysical chromatic sensitivity come to these limits, we developed a parameter-free model of stimulus encoding in the cone outer segments, and we compared the sensitivity of the model to the psychophysical sensitivity of monkeys performing a detection task and to the sensitivity of individual V1 neurons. Modeled cones had a temporal impulse response and a noise power spectrum that were derived from in vitro recordings of macaque cones, and V1 recordings were made during performance of the detection task. The sensitivity of the simulated cone mosaic, the V1 neurons, and the monkeys were tightly yoked for low-spatiotemporal-frequency isoluminant modulations, indicating high-fidelity signal transmission for this class of stimuli. Under the conditions of our experiments and the assumptions for our model, the signal-to-noise ratio for these stimuli dropped by a factor of ∼3 between the cones and perception. Populations of weakly correlated V1 neurons narrowly exceeded the monkeys' chromatic sensitivity but fell well short of the cones' chromatic sensitivity, suggesting that most of the behavior-limiting noise lies between the cone outer segments and the output of V1. The sensitivity gap between the cones and behavior for achromatic stimuli was larger than for chromatic stimuli, indicating greater postreceptoral noise. The cone mosaic model provides a means to compare visual sensitivity across disparate stimuli and to identify sources of noise that limit visual sensitivity.

V1 mechanisms underlying chromatic contrast detection.

To elucidate the cortical mechanisms of color vision, we recorded from individual primary visual cortex (V1) neurons in macaque monkeys performing a chromatic detection task. Roughly 30% of the neurons that we encountered were unresponsive at the monkeys' psychophysical detection threshold (PT). The other 70% were responsive at threshold but on average, were slightly less sensitive than the monkey. For these neurons, the relationship between neurometric threshold (NT) and PT was consistent across the four isoluminant color directions tested. A corollary of this result is that NTs were roughly four times lower for stimuli that modulated the long- and middle-wavelength sensitive cones out of phase. Nearly one-half of the neurons that responded to chromatic stimuli at the monkeys' detection threshold also responded to high-contrast luminance modulations, suggesting a role for neurons that are jointly tuned to color and luminance in chromatic detection. Analysis of neuronal contrast-response functions and signal-to-noise ratios yielded no evidence for a special set of "cardinal color directions," for which V1 neurons are particularly sensitive. We conclude that at detection threshold--as shown previously with high-contrast stimuli-V1 neurons are tuned for a diverse set of color directions and do not segregate naturally into red-green and blue-yellow categories.

Nonlinear analysis of macaque V1 color tuning reveals cardinal directions for cortical color processing.

Understanding color vision requires knowing how signals from the three classes of cone photoreceptor are combined in the cortex. We recorded from individual neurons in the primary visual cortex (V1) of awake monkeys while an automated, closed-loop system identified stimuli that differed in cone contrast but evoked the same response. We found that isoresponse surfaces for half the neurons were planar, which is consistent with linear processing. The remaining isoresponse surfaces were nonplanar. Some were cup-shaped, indicating sensitivity to only a narrow region of color space. Others were ellipsoidal, indicating sensitivity to all color directions. The major and minor axes of these nonplanar surfaces were often aligned to a set of three color directions that were previously identified in perceptual experiments. These results suggest that many V1 neurons combine cone signals nonlinearly and provide a new framework in which to decipher color processing in V1.

Effects of microsaccades on contrast detection and V1 responses in macaques.

Microsaccades can elevate contrast detection thresholds of human observers and modulate the activity of neurons in monkey visual cortex. Whether microsaccades elevate contrast detection thresholds in monkey observers is not known and bears on the interpretation of neurophysiological experiments. To answer this question, we trained two monkeys to perform a 2AFC contrast detection task. Performance was worse on trials in which a microsaccade occurred during the stimulus presentation. The magnitude of the effect was modest (threshold changes of <0.2 log unit) and color specific: achromatic sensitivity was impaired, but red-green sensitivity was not. To explore the neural basis of this effect, we recorded the responses of individual V1 neurons to a white noise stimulus. Microsaccades produced a suppression of spiking activity followed by an excitatory rebound that was similar for L - M cone-opponent and L + M nonopponent V1 neurons. We conclude that microsaccades in the monkey increase luminance contrast detection thresholds and modulate the spiking activity of V1 neurons, but the luminance specificity of the behavioral suppression is likely implemented downstream of V1.