Binocular Disparity Selectivity Weakened after Monocular Deprivation in Mouse V1

Abstract

Experiences during the critical period sculpt the circuitry within the neocortex, leading to changes in the functional responses of sensory neurons. Monocular deprivation (MD) during the visual critical period causes shifts in ocular preference, or dominance, toward the open eye in primary visual cortex (V1) and disrupts the normal development of acuity. In carnivores and primates, MD also disrupts the emergence of binocular disparity selectivity, a cue resulting from integrating ocular inputs. This disruption may be a result of the increase in neurons driven exclusively by the open eye that follows deprivation or a result of a mismatch in the convergence of ocular inputs. To distinguish between these possibilities, we measured the ocular dominance (OD) and disparity selectivity of neurons from male and female mouse V1 following MD. Normal mouse V1 neurons are dominated by contralateral eye input and contralateral eye deprivation shifts mouse V1 neurons toward more balanced responses between the eyes. This shift toward binocularity, as assayed by OD, decreased disparity sensitivity. MD did not alter the initial maturation of binocularity, as disparity selectivity before the MD was indistinguishable from normal mature animals. Decreased disparity tuning was most pronounced in binocular and ipsilaterally biased neurons, which are the populations that have undergone the largest shifts in OD. In concert with the decline in disparity selectivity, we observed a shift toward lower spatial frequency selectivity for the ipsilateral eye following MD. These results suggest an emergence of novel synaptic inputs during MD that disrupt the representation of disparity selectivity.SIGNIFICANCE STATEMENT We demonstrate that monocular deprivation during the developmental critical period impairs binocular integration in mouse primary visual cortex. This impairment occurs despite an increase in the degree to which neurons become more binocular. We further demonstrate that our deprivation did not impair the maturation of disparity selectivity. Disparity selectivity has already reached a matured level before the monocular deprivation. The loss of disparity tuning is primarily observed in neurons dominated by the open eye, suggesting a link between altered inputs and loss of disparity sensitivity. These results suggest that new inputs following deprivation may not maintain the precise spatial relationship between the two eye inputs required for disparity selectivity.

Keywords: binocular disparity; critical period; monocular deprivation; mouse visual cortex; plasticity.

Figure 1.

Potential changes to disparity selectivity following MD. A, Normal adult mouse visual cortical neurons are contralaterally biased by monocular stimuli but can be sensitive to binocular disparity by receiving weak ipsilateral inputs. Disparity selectivity formed from the convergence of distributions of contralateral and ipsilateral inputs representing distinct locations in visual space. B, MD of the dominant eye leads to a shift in ocular preference such that neurons are more binocular by monocular stimulation. Increased binocularity could increase disparity selectivity by the enhancement of excitatory input from the weak eye (left). Disparity selectivity could be decreased if the ipsilateral input no longer provides the spatial signal necessary for generating disparity selectivity (right).

Figure 2.

Two-photon imaging of binocular disparity selectivity in neurons from mouse V1 binocular zone. A–D, Example of calcium responses in a binocular neuron evoked by a range of binocular disparities (0–315 degrees), monocular stimulation of each eye, and a mean luminance screen. Gray represents individual traces. Black represents trial-average mean. Illustration of each stimulus shown above response traces. Scale bar indicates 10% change in fluorescence (ΔF/F) and 2 s duration. Mean ± SE of peak ΔF/F shown in a tuning curve. Two-photon images (right) show fluorescence from OGB-1 AM dye. Drifting gratings used to measure these responses had a spatial frequency of 0.02 cycles/degree. A, B, Example neurons from a normal animal with different ocular preferences, but both selective to binocular disparity. C, D, Example neurons from an animal with 4 d MD during the CP. E, Population OD distribution from normal animals. F, Population OD distribution from animals with 4 d MD. G, Cumulative OD distributions from normal and MD animals showing the shift toward binocularity in the MD animals. H, Population distribution of DSI for cells from normal animals. I, Population distribution of DSI for cells from animals with MD. J, Cumulative distributions for DSI from normal and MD animals showing the shift toward lowed disparity selectivity following MD.

Figure 3.

Disparity selectivity formed before the CP. A, B, Example tuning responses from neurons in an animal imaged before the CP. Both binocular and monocular neurons, as defined by OD, are sensitive for binocular disparity. Drifting gratings used to measure these responses had a spatial frequency of 0.02 cycles/degree. C, OD distribution from animals before the CP (left). Cumulative distributions from pre-CP and post-CP animals show similar OD (right). D, Distribution for DSI from animals before the CP (left). Cumulative distributions from pre-CP and post-CP animals show identical disparity selectivity (right).

Figure 4.

Decreased disparity selectivity selectively found in binocular and ipsilateral dominant neurons. Disparity selectivity for normal pre-CP (light blue), normal post-CP (dark blue), and deprived animals (purple) are shown for different OD groups. Each point indicates mean ± SE. Filled circles represent significantly different values compared with normal post-CP animals.

Figure 5.

Response amplitude for preferred binocular disparity. Magnitude of calcium responses to the preferred binocular disparity for cells from normal pre-CP (light blue), normal post-CP (dark blue), and deprived animals (purple), shown for different OD groups. Each point indicates mean ± SE. Filled circles represent significantly different values compared with normal post-CP animals.

Figure 6.

Loss of spatial acuity in the nondeprived eye. A, Spatial frequency tuning of example neurons from normal (left, open circles) and deprived (right, filled squares) animals. Responses shown here are for ipsilateral eye visual stimulation with a vertical grating. Mean ± SE of peak ΔF/F along with fits for spatial frequency selectivity (see Materials and Methods). B, The spatial resolution for the contralateral (blue) and ipsilateral (red) eye stimulation. Histograms of the spatial resolution are shown for both normal animals as well as animals following MD (gray background). Black arrows indicate geometric mean. C, The peak spatial frequency for the contralateral (blue) and ipsilateral (red) eye stimulation. Histograms of the preferred spatial frequency are shown for both normal animals as well as animals following MD (gray background). Black arrows indicate geometric mean.