Post-error recruitment of frontal sensory cortical projections promotes attention in mice.

The frontal cortex, especially the anterior cingulate cortex area (ACA), is essential for exerting cognitive control after errors, but the mechanisms that enable modulation of attention to improve performance after errors are poorly understood. Here we demonstrate that during a mouse visual attention task, ACA neurons projecting to the visual cortex (VIS; ACAVIS neurons) are recruited selectively by recent errors. Optogenetic manipulations of this pathway collectively support the model that rhythmic modulation of ACAVIS neurons in anticipation of visual stimuli is crucial for adjusting performance following errors. 30-Hz optogenetic stimulation of ACAVIS neurons in anesthetized mice recapitulates the increased gamma and reduced theta VIS oscillatory changes that are associated with endogenous post-error performance during behavior and subsequently increased visually evoked spiking, a hallmark feature of visual attention. This frontal sensory neural circuit links error monitoring with implementing adjustments of attention to guide behavioral adaptation, pointing to a circuit-based mechanism for promoting cognitive control.

Feedback inhibition derived from the posterior parietal cortex regulates the neural properties of the mouse visual cortex.

Feedback regulation from the higher association areas is thought to control the primary sensory cortex, contribute to the cortical processing of sensory information, and work for higher cognitive functions such as multimodal integration and attentional control. However, little is known about the underlying neural mechanisms. Here, we show that the posterior parietal cortex (PPC) persistently inhibits the activity of the primary visual cortex (V1) in mice. Activation of the PPC causes the suppression of visual responses in V1 and induces the short-term depression, which is specific to visual stimuli. In contrast, pharmacological inactivation of the PPC or disconnection of cortical pathways from the PPC to V1 results in an effect of transient enhancement of visual responses in V1. Two-photon calcium imaging demonstrated that the cortical disconnection caused V1 excitatory neurons an enhancement of visual responses and a reduction of orientation selectivity index (OSI). These results show that the PPC regulates the response properties of V1 excitatory neurons. Our findings reveal one of the functions of the PPC, which may contribute to higher brain functions in mice.

Molecular diversity of clustered protocadherin-α required for sensory integration and short-term memory in mice.

Clustered protocadherins (Pcdhs) are neuronal cell adhesion molecules characterized by homophilic adhesion between the tetramers of 58 distinct isoforms in mice. The diversity of Pcdhs and resulting highly-specific neuronal adhesion may be required for the formation of neural circuits for executing higher brain functions. However, this hypothesis remains to be tested, because knockout of Pcdh genes produces abnormalities that may interfere with higher brain functions indirectly. In Pcdh-α1,12 mice, only α1, α12 and two constitutive isoforms are expressed out of 14 isoforms. The appearance and behavior of Pcdh-α1,12 mice are similar to those of wild-type mice, and most abnormalities reported in Pcdh-α knockout mice are not present in Pcdh-α1,12 mice. We examined Pcdh-α1,12 mice in detail, and found that cortical depression induced by sensory mismatches between vision and whisker sensation in the visual cortex was impaired. Since Pcdh-α is densely distributed over the cerebral cortex, various types of higher function are likely impaired in Pcdh-α1,12 mice. As expected, visual short-term memory of space/shape was impaired in behavioral experiments using space/shape cues. Furthermore, behavioral learning based on audio-visual associative memory was also impaired. These results indicate that the molecular diversity of Pcdh-α plays essential roles for sensory integration and short-term memory.

Impaired clustered protocadherin-α leads to aggregated retinogeniculate terminals and impaired visual acuity in mice.

Clustered protocadherins (cPcdhs) comprising cPcdh-α, -ß, and -γ, encode a large family of cadherin-like cell-adhesion molecules specific to neurons. Impairment of cPcdh-α results in abnormal neuronal projection patterns in specific brain areas. To elucidate the role of cPcdh-α in retinogeniculate projections, we investigated the morphological patterns of retinogeniculate terminals in the lateral geniculate (LG) nucleus of mice with impaired cPcdh-α. We found huge aggregated retinogeniculate terminals in the dorsal LG nucleus, whereas no such aggregated terminals derived from the retina were observed in the olivary pretectal nucleus and the ventral LG nucleus. These aggregated terminals appeared between P10 and P14, just before eye opening and at the beginning of the refinement stage of the retinogeniculate projections. Reduced visual acuity was observed in adult mice with impaired cPcdh-α, whereas the orientation selectivity and direction selectivity of neurons in the primary visual cortex were apparently normal. These findings suggest that cPcdh-α is required for adequate spacing of retinogeniculate projections, which may be essential for normal development of visual acuity.

Visual map shifts based on whisker-guided cues in the young mouse visual cortex.

Mice navigate nearby space using their vision and whiskers, and young mice learn to integrate these heterogeneous inputs in perceptual space. We found that cortical responses were depressed in the primary visual cortex of young mice after wearing a monocular prism. This depression was uniformly observed in the primary visual cortex and was eliminated by whisker trimming or lesions in the posterior parietal cortex. Compensatory visual map shifts of responses elicited via the eye that had worn the prism were also observed. As a result, cortical responses elicited via each eye were clearly separated when a visual stimulus was placed in front of the mice. A comparison of response areas before and after prism wearing indicated that the map shifts were produced by depression with spatial eccentricity. Visual map shifts based on whisker-guided cues may serve as a model for investigating the cellular and molecular mechanisms underlying higher sensory integration in the mammalian brain.