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Intrinsic signal optical imaging (ISI) is a rapid and noninvasive method for observing brain activity in vivo over a large area of the cortex. Here we describe our protocol for mapping retinotopy to identify mouse visual cortical areas using ISI. First, surgery is performed to attach a head frame to the mouse skull (∼1 h). The next day, intrinsic activity across the visual cortex is recorded during the presentation of a full-field drifting bar in the horizontal and vertical directions (∼2 h). Horizontal and vertical retinotopic maps are generated by analyzing the response of each pixel during the period of the stimulus. Last, an algorithm uses these retinotopic maps to compute the visual field sign and coverage, and automatically construct visual borders without human input. Compared with conventional retinotopic mapping with episodic presentation of adjacent stimuli, a continuous, periodic stimulus is more resistant to biological artifacts. Furthermore, unlike manual hand-drawn approaches, we present a method for automatically segmenting visual areas, even in the small mouse cortex. This relatively simple procedure and accompanying open-source code can be implemented with minimal surgical and computational experience, and is useful to any laboratory wishing to target visual cortical areas in this increasingly valuable model system.

A characteristic feature in the primary visual cortex is that visual responses are suppressed as a stimulus extends beyond the classical receptive field. Here, we examined the role of inhibitory neurons expressing somatostatin (SOM⁺) or parvalbumin (PV⁺) on surround suppression and preferred receptive field size. We recorded multichannel extracellular activity in V1 of transgenic mice expressing channelrhodopsin in SOM⁺ neurons or PV⁺ neurons. Preferred size and surround suppression were measured using drifting square-wave gratings of varying radii and at two contrasts. Consistent with findings in primates, we found that the preferred size was larger for lower contrasts across all cortical depths, whereas the suppression index (SI) showed a trend to decrease with contrast. We then examined the effect of these metrics on units that were suppressed by photoactivation of either SOM⁺ or PV⁺ neurons. When activating SOM⁺ neurons, we found a significant increase in SI at cortical depths >400 μm, whereas activating PV⁺ neurons caused a trend toward lower SIs regardless of cortical depth. Conversely, activating PV⁺ neurons significantly increased preferred size across all cortical depths, similar to lowering contrast, whereas activating SOM⁺ neurons had no systematic effect on preferred size across all depths. These data suggest that SOM⁺ and PV⁺ neurons contribute differently to spatial integration. Our findings are compatible with the notion that SOM⁺ neurons mediate surround suppression, particularly in deeper cortex, whereas PV⁺ activation decreases the drive of the input to cortex and therefore resembles the effects on spatial integration of lowering contrast.

The visual system adapts to maintain sensitivity and selectivity over a large range of luminance intensities. One way that the retina maintains sensitivity across night and day is by switching between rod and cone photoreceptors, which alters the receptive fields and interneuronal correlations of retinal ganglion cells (RGCs). While these adaptations allow the retina to transmit visual information to the brain across environmental conditions, the code used for that transmission varies. To determine how downstream targets encode visual scenes across light levels, we measured the effects of luminance adaptation on thalamic and cortical population activity. While changes in the retinal output are evident in the lateral geniculate nucleus (LGN), selectivity in the primary visual cortex (V1) is largely invariant to the changes in luminance. We show that the visual system could maintain sensitivity across environmental conditions without altering cortical selectivity through the convergence of parallel functional pathways from the thalamus to the cortex. [Display omitted] • Adaptation alters the thalamic neural code between scotopic and photopic luminance • Visual cortex exhibits largely luminance-invariant selectivity and noise correlations • The convergence of parallel pathways can generate a luminance-invariant code O'Shea et al. investigates how the transition between cone- and rod-mediated vision affects neural representations in central visual areas of the mouse. Whereas the thalamus inherits luminance-dependent functional properties from the retina, visual cortex exhibits a luminance-invariant code. The convergence of parallel afferent pathways can generate a luminance-invariant code. [ABSTRACT FROM AUTHOR]

To guide future experiments aimed at understanding the mouse visual system, it is essential that we have a solid handle on the global topography of visual cortical areas. Ideally, the method used to measure cortical topography is objective, robust, and simple enough to guide subsequent targeting of visual areas in each subject. We developed an automated method that uses retinotopic maps of mouse visual cortex obtained with intrinsic signal imaging (Schuett et al., 2002; Kalatsky and Stryker, 2003; Marshel et al., 2011) and applies an algorithm to automatically identify cortical regions that satisfy a set of quantifiable criteria for what constitutes a visual area. This approach facilitated detailed parcellation of mouse visual cortex, delineating nine known areas (primary visual cortex, lateromedial area, anterolateral area, rostrolateral area, anteromedial area, posteromedial area, laterointermediate area, posterior area, and postrhinal area), and revealing two additional areas that have not been previously described as visuotopically mapped in mice (laterolateral anterior area and medial area). Using the topographic maps and defined area boundaries from each animal, we characterized several features of map organization, including variability in area position, area size, visual field coverage, and cortical magnification. We demonstrate that higher areas in mice often have representations that are incomplete or biased toward particular regions of visual space, suggestive of specializations for processing specific types of information about the environment. This work provides a comprehensive description of mouse visuotopic organization and describes essential tools for accurate functional localization of visual areas. [ABSTRACT FROM AUTHOR]

Numerous studies have revealed traveling waves of activity in sensory cortex, both following sensory stimulation and during ongoing activity. We contributed to this body of work by measuring the spike-triggered average of the local field potential (stLFP) at multiple concurrent locations (Nauhaus et al., 2009) in the visual cortex of anesthetized cats and macaques.Wefound the stLFP to be progressively delayed at increasing distances from the site of the triggering spikes, and interpreted this as a traveling wave of depolarization originating from that site. Our results were criticized, however, on two grounds. First, a study using the same recording techniques in the visual cortex of awake macaques reported an apparent lack of traveling waves, and proposed that traveling waves could arise artifactually from excessive filtering of the field potentials (Ray and Maunsell, 2011). Second, the interpretability of the stLFP was questioned (Kenneth Miller, personal communication), as the stLFP must reflect not only interactions between spike trains and field potentials, but also correlations within and across the spike trains. Here, we show that our data and interpretation are not imperiled by these criticisms. We reanalyzed our field potentials to remove any possible artifact due to filtering and to discount the effects of correlations within and across the triggering spike trains. In both cases, we found that the traveling waves were still present. In fact, closer inspection of Ray and Maunsell's (2011) data from awake cortex shows that they do agree with ours, as they contain clear evidence for traveling waves. [ABSTRACT FROM AUTHOR]

Neurons in visual cortex are linked by an extensive network of lateral connections. To study the effect of these connections on neural responses, we recorded spikes and local field potentials (LFPs) from multi-electrode arrays that were implanted in monkey and cat primary visual cortex. Spikes at each location generated outward traveling LFP waves. When the visual stimulus was absent or had low contrast, these LFP waves had large amplitudes and traveled over long distances. Their effect was strong: LFP traces at any site could be predicted by the superposition of waves that were evoked by spiking in a ∼1.5-mm radius. As stimulus contrast increased, both the magnitude and the distance traveled by the waves progressively decreased. We conclude that the relative weight of feedforward and lateral inputs in visual cortex is not fixed, but rather depends on stimulus contrast. Lateral connections dominate at low contrast, when spatial integration of signals is perhaps most beneficial. [ABSTRACT FROM AUTHOR]

A correction to the article "Orthogonal micro-organization of orientation and spatial frequency in primate primary visual cortex" in the November 2012 issue is presented which mentions the incorrect computation performed to yield the values in the text and on the axis label.

We studied the relative accuracy of drifting gratings and noise stimuli for functionally characterizing neural populations using two-photon calcium imaging. Calcium imaging has the potential to distort measurements due to nonlinearity in the conversion from spikes to observed fluorescence. We demonstrate a dramatic impact of fluorescence saturation on functional measurements in ferret V1 by showing that responses to drifting gratings strongly violate contrast invariance of orientation tuning, a fundamental property of the spike rates. The observed relationship is consistent with saturation that clips the high-contrast tuning curve peaks by ∼40%. The nonlinearity was also apparent in mouse V1 responses to drifting gratings, but not as strong as in the ferret. Contrast invariance holds, however, for tuning curves measured with a randomized grating stimulus. This finding is consistent with prior work showing that the linear portion of a linear-nonlinear system can be recovered with reverse correlation. Furthermore, we demonstrate that a noise stimulus is more effective at keeping spike rates in the linear operating regime of a saturating nonlinearity, which both maximizes signal-to-noise ratios and simplifies the recovery of fast spike dynamics from slow calcium transients. Finally, we uncover spatiotemporal receptive fields by removing the nonlinearity and slow calcium transient from a model of fluorescence generation, which allowed us to observe dynamic sharpening of orientation tuning. We conclude that for two-photon recordings it is imperative that one considers the nonlinear distortion when designing stimuli and interpreting results, especially in sensory areas, species, or cell types with high firing rates.