Humans are less likely to learn from individuals belonging to a different group (outgroup) than from individuals of their own group (ingroup), yet the source of this societally relevant deficit has remained unclear. Here we used neuroimaging and computational modeling to investigate how people learn from observing the actions and outcomes of ingroup and outgroup demonstrators. Politically left-wing male and female participants performed worse when observing computer-simulated actions they believed were from a right-wing outgroup member compared with those from a left-wing ingroup member. A control experiment in which participants observed choices from a nonhuman agent confirmed that this performance difference reflected an outgroup deficit, rather than an ingroup gain. Accounting for the outgroup deficit, a computational model showed that participants relied less on information from outgroup actions compared with ingroup actions, while learning from outgroup outcomes was not impaired. At the neural level, ...

Functional connectivity of neural oscillations (oscillation-based FC) is thought to afford dynamic information exchange across task-relevant neural ensembles. Although oscillation-based FC is classically defined relative to a prestimulus baseline, giving rise to rapid, context-dependent changes in individual connections, studies of distributed spatial patterns show that oscillation-based FC is omnipresent, occurring even in the absence of explicit cognitive demands. Thus, the issue of whether oscillation-based FC is primarily shaped by cognitive state or is intrinsic in nature remains open. Accordingly, we sought to reconcile these observations by interrogating the ECoG recordings of 18 presurgical human patients (8 females) for state dependence of oscillation-based FC in five canonical frequency bands across an array of six task states. FC analysis of phase and amplitude coupling revealed a highly similar, largely state-invariant (i.e., intrinsic) spatial component across cognitive states. This spatial or...

The lateral line (LL) is a sensory system that allows fish and amphibians to detect water currents. LL responsiveness is modulated by efferent neurons that aid in distinguishing between external and self-generated stimuli, maintaining sensitivity to relevant cues. One component of the efferent system is cholinergic, the activation of which inhibits afferent activity. LL hair cells (HCs) share structural, functional, and molecular similarities with those of the cochlea, making them a popular model for studying human hearing and balance disorders. Because of these commonalities, one could propose that the receptor at the LL efferent synapse is a α9α10 nicotinic acetylcholine receptor (nAChR). However, the identities of the molecular players underlying ACh-mediated inhibition in the LL remain unknown. Surprisingly, through the analysis of single-cell expression studies and in situ hybridization, we describe that α9, but not the α10, subunits are enriched in zebrafish HCs. Moreover, the heterologous expression...

Throughout the nervous system, the convergence of two or more presynaptic inputs on a target cell is commonly observed. The question we ask here is to what extent converging inputs influence each other’s structural and functional synaptic plasticity. In complex circuits, isolating individual inputs is difficult because postsynaptic cells can receive thousands of inputs. An ideal model to address this question is the Drosophila larval neuromuscular junction (NMJ) where each postsynaptic muscle cell receives inputs from two glutamatergic types of motor neurons (MNs), known as 1b and 1s MNs. Notably, each muscle is unique and receives input from a different combination of 1b and 1s MNs; we surveyed multiple muscles for this reason. Here, we identified a cell-specific promoter that allows ablation of 1s MNs post-innervation and measured structural and functional responses of convergent 1b NMJs using microscopy and electrophysiology. For all muscles examined in both sexes, ablation of 1s MNs resulted in NMJ exp...

Critical periods are developmental windows during which neural circuits effectively adapt to the new sensory environment. Animal models of Fragile X syndrome (FXS), a common monogenic autism spectrum disorder (ASD), exhibit profound impairments of sensory experience-driven critical periods. However, it is not known whether the causative Fragile X Mental Retardation Protein (FMRP) acts uniformly across neurons, or instead manifests neuron-specific functions. Here, we use the genetically-tractable Drosophila brain antennal lobe (AL) olfactory circuit of both sexes to investigate neuron-specific FMRP roles in the odorant experience-dependent remodeling of the olfactory sensory neuron (OSN) innervation during an early-life critical period. We find targeted OSN class-specific FMRP RNAi impairs innervation remodeling within AL synaptic glomeruli, whereas global dfmr1 null mutants display relatively normal odorant-driven refinement. We find both OSN cell autonomous and cell non-autonomous FMRP functions mediate o...

Drug-induced neuroadaptations in the medial prefrontal cortex (mPFC) have been implicated in addictive behaviors. Repeated cocaine exposure has been shown to increase pyramidal neuron excitability in the prelimbic (PL) region of the mouse mPFC, an adaptation attributable to a suppression of G protein-gated inwardly rectifying K+ (GIRK) channel activity. After establishing that this neuroadaptation is not seen in adjacent GABA neurons, we employed viral GIRK channel ablation and complementary chemogenetic approaches to selectively enhance PL pyramidal neuron excitability in adult mice, in order to evaluate the impact of this form of plasticity on PL-dependent behaviors. GIRK channel ablation decreased somatodendritic GABAB receptor-dependent signaling and rheobase in PL pyramidal neurons. This manipulation also enhanced the motor-stimulatory effect of cocaine but did not impact baseline activity or trace fear learning. In contrast, selective chemogenetic excitation of PL pyramidal neurons, or chemogenetic i...

Intrinsically photosensitive retinal ganglion cells (ipRGCs) exhibit melanopsin-dependent light responses that persist in the absence of rod and cone photoreceptor-mediated input. In addition to signaling anterogradely to the brain, ipRGCs signal retrogradely to intraretinal circuitry via gap junction-mediated electrical synapses with amacrine cells (ACs). However, the targets and functions of these intraretinal signals remain largely unknown. Here, in mice of both sexes, we identify circuitry that enables M5 ipRGCs to locally inhibit retinal neurons via electrical synapses with a non-spiking GABAergic AC. During pharmacological blockade of rod- and cone-mediated input, whole-cell recordings of corticotropin-releasing hormone-expressing (CRH+) ACs reveal persistent visual responses that require both melanopsin expression and gap junctions. In the developing retina, ipRGC-mediated input to CRH+ ACs is weak or absent prior to eye opening, indicating a primary role for this input in the mature retina, i.e., i...

Cell adhesion proteins of the Cadm (SynCAM/Necl) family regulate myelination and the organization of myelinated axons. In the peripheral nervous system, intercellular contact between Schwann cells and their underlying axons is believed to be mediated by binding of glial Cadm4 to axonal Cadm3 or Cadm2. Nevertheless, given that distinct neurons express different combinations of the Cadm proteins, the identity of the functional axonal ligand for Cadm4 remains to be determined. Here we took a genetic approach to compare the phenotype of Cadm4 null mice, which exhibit abnormal distribution of Caspr and Kv1 potassium channels, with mice lacking different combinations of Cadm1 - Cadm3 genes. We show that in contrast to mice lacking the single Cadm1 , Cadm2 , or Cadm3 genes, genetic ablation of all three phenocopies the abnormalities detected in the absence of Cadm4. Similar defects were observed in double mutant mice lacking Cadm3 and Cadm2 (i.e., Cadm3-/-/Cadm2-/- ) or Cadm3 and Cadm1 (i.e., Cadm3-/-/Cadm1-/- ),...

Attentional selection is a function that allocates the brain’s computational resources to the most important part of a visual scene at a specific moment. Saliency map models have been proposed as computational models to predict attentional selection within a spatial location. Recent saliency map models based on deep convolutional neural networks (DCNNs) exhibit the highest performance for predicting the location of attentional selection and human gaze, which reflect overt attention. Trained DCNNs potentially provide insight into the perceptual mechanisms of biological visual systems. However, the relationship between artificial and neural representations used for determining attentional selection and gaze location remains unknown. To understand the mechanism underlying saliency map models based on DCNNs and the neural system of attentional selection, we investigated the correspondence between layers of a DCNN saliency map model and monkey visual areas for natural image representations. We compared the char...

The development of deep convolutional neural networks (CNNs) has recently led to great successes in computer vision, and CNNs have become de facto computational models of vision. However, a growing body of work suggests that they exhibit critical limitations on tasks beyond image categorization. Here, we study one such fundamental limitation, concerning the judgment of whether two simultaneously presented items are the same or different (SD) compared with a baseline assessment of their spatial relationship (SR). In both human subjects and artificial neural networks, we test the prediction that SD tasks recruit additional cortical mechanisms which underlie critical aspects of visual cognition that are not explained by current computational models. We thus recorded electroencephalography (EEG) signals from human participants engaged in the same tasks as the computational models. Importantly, in humans the two tasks were matched in terms of difficulty by an adaptive psychometric procedure; yet, on top of a mo...