Broadening of Inhibitory Tuning Underlies Contrast-Dependent Sharpening of Orientation Selectivity in Mouse Visual Cortex

Abstract

Orientation selectivity (OS) in the visual cortex has been found to be invariant to increases in stimulus contrast, a finding that cannot be accounted for by the original, purely excitatory Hubel and Wiesel model. This property of OS may be important for preserving the quality of perceived stimulus across a range of stimulus intensity. The synaptic mechanisms that can prevent a broadening of OS caused by contrast-dependent strengthening of excitatory inputs to cortical neurons remain unknown. Using in vivo loose-patch recordings, we found in excitatory neurons in layer 4 of mouse primary visual cortex (V1) that the spike response to the preferred orientation was elevated as contrast increased while that to the orthogonal orientation remained unchanged, resulting in an overall sharpening rather than a weakening of OS. Whole-cell voltage-clamp recordings further revealed that contrast increases resulted in a scaling up of excitatory conductance at all stimulus orientations. Inhibitory conductance was enhanced at a similar level as excitation for the preferred orientation, but at a significantly higher level for the orthogonal orientation. Modelling revealed that the resulting broadening of inhibitory tuning is critical for maintaining and sharpening OS at high contrast. Finally, two-photon imaging guided recordings from parvalbumin-positive (PV) inhibitory neurons revealed that the broadening of inhibition can be attributed to a contrast-dependent broadening of spike response tuning of PV neurons. Together our results suggest that modulation of synaptic inhibition in the mouse V1 cortical circuit preserves the sharpness of response selectivity during changes of stimulus strength.

Cross-Modality Sharpening of Visual Cortical Processing through Layer-1-Mediated Inhibition and Disinhibition

“…The increase in gOSI was 25% at 25% contrast, and 15% at 95% contrast. With the visual stimulation alone, orientation tuning was sharper at the higher contrast (gOSI = 0.37 ± 0.12 and 0.46 ± 0.13 at 25% and 95% contrast respectively, p < 0.01, paired t-test, n = 10), consistent with our previous report (Li et al, 2012a). In L4, however, stimulating A1-V1 axons did not have any significant effect on orientation tuning or evoked firing rates (Figure 3K-3R, and Figure S3D-S3E).…”

Binocular Input Coincidence Mediates Critical Period Plasticity in the Mouse Primary Visual Cortex

“…The laminae were roughly identified based on the density of cell stained with DAPI (4Ј,6Ј-diamidino-2-phenylindole dihydrochloride). The average thickness of the mouse visual cortices was 996 Ϯ 43 m (eight mice), 1053 Ϯ 36 m (eight mice), and 1068 Ϯ 31 m (five mice) at P17-P19, P27-P29, and ϳP60, respectively, and correspondingly the layer 4 was located in the range of about 350 -490, 360 -500, and 360 -500 m. This laminar depth characterization is comparable to findings in previous studies (Li et al, 2012). Fluorescence images were acquired by a Nikon A1R confocal microscope with a 20ϫ objective lens.…”

“…The construction of highly organized neural circuits requires an activity-dependent refinement of early diffuse synaptic connections after their initial formation (Shatz, 1990;Katz and Shatz, 1996). It has been shown that correlated neuronal activities in the retina (Galli and Maffei, 1988;Meister et al, 1991;Wong et al, 1993), dorsal LGN (Weliky and Katz, 1999), and V1 (Chiu and Weliky, 2002) are critical for instructing the formation of eyespecific segregation of afferent eye inputs at different levels of the visual processing pathway (Stryker and Harris, 1986;Cang et al, 2005;Del Rio and Feller, 2006;Huberman et al, 2006).…”

“…However, how the enhanced inhibition differentially regulates response latency is unclear. One possible mechanism is that enhancing GABA transmission could enforce the temporal precision of spike output (Pouille and Scanziani, 2001;Mittmann et al, 2005) and consequently strengthen the coherence of convergent presynaptic cell inputs (Kuhlman et al, 2010;H. P. Wang et al, 2010), which may decrease the response latency along the visual pathway.…”

“…This is best exemplified by visual input-dependent ocular dominance (OD) plasticity of developing primary visual cortex (V1) in mammals, such as monkey (Hubel et al, 1977;LeVay et al, 1980), cat (Wiesel and Hubel, 1963;Hubel and Wiesel, 1970;Shatz and Stryker, 1978), ferret (Issa et al, 1999), and rodents (Dräger, 1978;Maffei et al, 1992;Gordon and Stryker, 1996;Frenkel and Bear, 2004), whereby 3-4 d of closure of one eye [monocular deprivation (MD)] during the CP causes a dramatic shift of the eye input preference of V1 neurons toward the nondeprived eye. Further studies with binocular occlusion (Wiesel and Hubel, 1965;Ohzawa and Freeman, 1988), alternating monocular occlusion (Hubel and Wiesel, 1965), artificial strabismus (Hubel and Wiesel, 1965;Maffei and Bisti, 1976;Smith et al, 1979), or stroboscopic rearing (Kennedy and Orban, 1983) in animals during the CP have demonstrated that correlated visual inputs between the two eyes are required for the competition between the afferents from the two eyes to their common cortical target cells. Moreover, theoretical and modeling studies have suggested that aspects of such experience-dependent synaptic competition between inputs from the two eyes to the developing V1 can be understood by considering synaptic learning rules, such as correlation-based Hebbian modifications (Stent, 1973;Miller et al, 1989), spike rate-dependent Bienenstock-Cooper-Munro (BCM) rule (Bienenstock et al, 1982;Cooper and Bear, 2012), or spike timing-dependent synaptic plasticity (Song et al, 2000;Song and Abbott, 2001).…”