Corrective feedback guides human perceptual decision-making by informing about the world state rather than rewarding its choice.

Corrective feedback received on perceptual decisions is crucial for adjusting decision-making strategies to improve future choices. However, its complex interaction with other decision components, such as previous stimuli and choices, challenges a principled account of how it shapes subsequent decisions. One popular approach, based on animal behavior and extended to human perceptual decision-making, employs "reinforcement learning," a principle proven successful in reward-based decision-making. The core idea behind this approach is that decision-makers, although engaged in a perceptual task, treat corrective feedback as rewards from which they learn choice values. Here, we explore an alternative idea, which is that humans consider corrective feedback on perceptual decisions as evidence of the actual state of the world rather than as rewards for their choices. By implementing these "feedback-as-reward" and "feedback-as-evidence" hypotheses on a shared learning platform, we show that the latter outperforms the former in explaining how corrective feedback adjusts the decision-making strategy along with past stimuli and choices. Our work suggests that humans learn about what has happened in their environment rather than the values of their own choices through corrective feedback during perceptual decision-making.

Joint representations of color and form in mouse visual cortex described by random pooling from rods and cones.

Spatial transitions in color can aid any visual perception task, and its neural representation, the "integration of color and form," is thought to begin at primary visual cortex (V1). Integration of color and form is untested in mouse V1, yet studies show that the ventral retina provides the necessary substrate from green-sensitive rods and ultraviolet-sensitive cones. Here, we used two-photon imaging in V1 to measure spatial frequency (SF) tuning along four axes of rod and cone contrast space, including luminance and color. We first reveal that V1's sensitivity to color is similar to luminance, yet average SF tuning is significantly shifted lowpass for color. Next, guided by linear models, we used SF tuning along all four color axes to estimate the proportion of neurons that fall into classic models of color opponency, i.e., "single-," "double-," and "non-opponent." Few neurons (∼6%) fit the criteria for double opponency, which are uniquely tuned for chromatic borders. Most of the population can be described as a unimodal distribution ranging from strongly single-opponent to non-opponent. Consistent with recent studies of the rodent and primate retina, our V1 data are well-described by a simple model in which ON and OFF channels to V1 sample the photoreceptor mosaic randomly. Finally, an analysis comparing color opponency to preferred orientation and retinotopy further validates rods, and not cone M-opsin, as opponent with cone S-opsin in the upper visual field.NEW & NOTEWORTHY This study is the first to show that mouse V1 is highly sensitive to UV-green color contrast. Furthermore, it provides a detailed characterization of "color opponency," which is the putative neural basis for color perception. Finally, using an extremely simple yet novel random wiring model, we account for our observations.

Excitatory synapses and gap junctions cooperate to improve Pv neuronal burst firing and cortical social cognition in Shank2-mutant mice.

NMDA receptor (NMDAR) and GABA neuronal dysfunctions are observed in animal models of autism spectrum disorders, but how these dysfunctions impair social cognition and behavior remains unclear. We report here that NMDARs in cortical parvalbumin (Pv)-positive interneurons cooperate with gap junctions to promote high-frequency (>80 Hz) Pv neuronal burst firing and social cognition. Shank2-/- mice, displaying improved sociability upon NMDAR activation, show impaired cortical social representation and inhibitory neuronal burst firing. Cortical Shank2-/- Pv neurons show decreased NMDAR activity, which suppresses the cooperation between NMDARs and gap junctions (GJs) for normal burst firing. Shank2-/- Pv neurons show compensatory increases in GJ activity that are not sufficient for social rescue. However, optogenetic boosting of Pv neuronal bursts, requiring GJs, rescues cortical social cognition in Shank2-/- mice, similar to the NMDAR-dependent social rescue. Therefore, NMDARs and gap junctions cooperate to promote cortical Pv neuronal bursts and social cognition.

Sexually dimorphic behavior, neuronal activity, and gene expression in Chd8-mutant mice.

Autism spectrum disorders (ASDs) are four times more common in males than in females, but the underlying mechanisms are poorly understood. We characterized sexually dimorphic changes in mice carrying a heterozygous mutation in Chd8 (Chd8+/N2373K) that was first identified in human CHD8 (Asn2373LysfsX2), a strong ASD-risk gene that encodes a chromatin remodeler. Notably, although male mutant mice displayed a range of abnormal behaviors during pup, juvenile, and adult stages, including enhanced mother-seeking ultrasonic vocalization, enhanced attachment to reunited mothers, and isolation-induced self-grooming, their female counterparts do not. This behavioral divergence was associated with sexually dimorphic changes in neuronal activity, synaptic transmission, and transcriptomic profiles. Specifically, female mice displayed suppressed baseline neuronal excitation, enhanced inhibitory synaptic transmission and neuronal firing, and increased expression of genes associated with extracellular vesicles and the extracellular matrix. Our results suggest that a human CHD8 mutation leads to sexually dimorphic changes ranging from transcription to behavior in mice.

Maps of cone opsin input to mouse V1 and higher visual areas.

Studies in the mouse retina have characterized the spatial distribution of an anisotropic ganglion cell and photoreceptor mosaic, which provides a solid foundation to study how the cortex pools from afferent parallel color channels. In particular, the mouse's retinal mosaic exhibits a gradient of wavelength sensitivity along its dorsoventral axis. Cones at the ventral extreme mainly express S opsin, which is sensitive to ultraviolet (UV) wavelengths. Then, moving toward the retina's dorsal extreme, there is a transition to M-opsin dominance. Here, we tested the hypothesis that the retina's opsin gradient is recapitulated in cortical visual areas as a functional map of wavelength sensitivity. We first identified visual areas in each mouse by mapping retinotopy with intrinsic signal imaging (ISI). Next, we measured ISI responses to stimuli along different directions of the S- and M-color plane to quantify the magnitude of S and M input to each location of the retinotopic maps in five visual cortical areas (V1, AL, LM, PM, and RL). The results illustrate a significant change in the S:M-opsin input ratio along the axis of vertical retinotopy that is consistent with the gradient along the dorsoventral axis of the retina. In particular, V1 populations encoding the upper visual field responded to S-opsin contrast with 6.1-fold greater amplitude than to M-opsin contrast. V1 neurons encoding lower fields responded with 4.6-fold greater amplitude to M- than S-opsin contrast. The maps in V1 and higher visual areas (HVAs) underscore the significance of a wavelength sensitivity gradient for guiding the mouse's behavior.NEW & NOTEWORTHY Two elements of this study are particularly novel. For one, it is the first to quantify cone inputs to mouse visual cortex; we have measured cone input in five visual areas. Next, it is the first study to identify a feature map in the mouse visual cortex that is based on well-characterized anisotropy of cones in the retina; we have identified maps of opsin selectivity in five visual areas.

Enhanced Neuronal Activity in the Medial Prefrontal Cortex during Social Approach Behavior.

UNLABELLED: Although the medial prefrontal cortex (mPFC) is known to play a crucial role in rodent social behavior, little is known about mPFC neural correlates of social behavior. In the present study, we examined single-neuron activity in the mPFC of mice performing a modified version of the three-chamber test. We found that a subset of mPFC neurons elevate discharge rates when approaching a stranger mouse but not when approaching an inanimate object or an empty chamber. Our results reveal mPFC neural activity that is correlated with social approach behavior in a widely used social-interaction paradigm. These findings might be helpful for future investigations of mPFC neural processes underlying social interaction in health and disease. SIGNIFICANCE STATEMENT: Although the prefrontal cortex is known to play a crucial role in rodent social behavior, little is known about prefrontal neural correlates of social behavior. This study shows that the activity of a subset of prefrontal neurons increases in association with social approach behavior during a three-chamber test-a widely used behavioral paradigm. Such responses might be a signature of prefrontal neural processes underlying social approach behavior.

Social deficits in IRSp53 mutant mice improved by NMDAR and mGluR5 suppression.

Social deficits are observed in diverse psychiatric disorders, including autism spectrum disorders and schizophrenia. We found that mice lacking the excitatory synaptic signaling scaffold IRSp53 (also known as BAIAP2) showed impaired social interaction and communication. Treatment of IRSp53(-/-) mice, which display enhanced NMDA receptor (NMDAR) function in the hippocampus, with memantine, an NMDAR antagonist, or MPEP, a metabotropic glutamate receptor 5 antagonist that indirectly inhibits NMDAR function, normalized social interaction. This social rescue was accompanied by normalization of NMDAR function and plasticity in the hippocampus and neuronal firing in the medial prefrontal cortex. These results, together with the reduced NMDAR function implicated in social impairments, suggest that deviation of NMDAR function in either direction leads to social deficits and that correcting the deviation has beneficial effects.