Bayesian inference provides an elegant theoretical framework for understanding the characteristic biases and discrimination thresholds in visual speed perception. However, the framework is difficult to validate due to its flexibility and the fact that suitable constraints on the structure of the sensory uncertainty have been missing. Here, we demonstrate that a Bayesian observer model constrained by efficient coding not only well explains human visual speed perception but also provides an accurate quantitative account of the tuning characteristics of neurons known for representing visual speed. Specifically, we found that the population coding accuracy for visual speed in area MT (“neural prior”) is precisely predicted by the power-law, slow-speed prior extracted from fitting the Bayesian model to psychophysical data (“behavioral prior”) to the point that the two priors are indistinguishable in a cross-validation model comparison. Our results demonstrate a quantitative validation of the Bayesian observer m...

Dendrite and axon arbor sizes are critical to neuronal function and vary widely between different neuron types. The relative dendrite and axon sizes of synaptic partners control signal convergence and divergence in neural circuits. The developmental mechanisms that determine cell-type-specific dendrite and axon size and match synaptic partners' arbor territories remain obscure. Here, we discover that retinal horizontal cells express the leucine-rich repeat domain cell adhesion molecule AMIGO1. Horizontal cells provide pathway-specific feedback to photoreceptors: horizontal cell axons to rods and horizontal cell dendrites to cones. AMIGO1 selectively expands the size of horizontal cell axons. When Amigo1 is deleted in all or individual horizontal cells of either sex, their axon arbors shrink. By contrast, horizontal cell dendrites and synapse formation of horizontal cell axons and dendrites are unaffected by AMIGO1 removal. The dendrites of rod bipolar cells, which do not express AMIGO1, shrink in parallel ...

Dorsal root ganglion (DRG) neurons are classified into distinct types to mediate the somatosensation with different modalities. Recently, transcriptional profilings of DRG neurons by single-cell RNA-sequencing have provided new insights into the neuron typing and functional properties. Zinc-finger CCHC domain-containing 12 (Zcchc12) was reported to be the representative marker for a subtype of Gal-positive (Gal+) DRG neurons. However, the characteristics and functions of Zcchc12+ neurons are largely unknown. Here, we genetically labelled Zcchc12+ neurons in Zcchc12-CreERT2::Ai9 mice, and verified that Zcchc12 represented a new subpopulation of DRG neurons in both sexes. Zcchc12+ neurons centrally innervated the superficial laminae in spinal dorsal horn, and peripherally terminated as free nerve endings in the epidermis and cluster-shaped fibers in the dermis of footpads and nearby. Besides, Zcchc12+ neurons also formed circumferential endings surround the hair follicles in hairy skin. Functionally, in vivo...

Disorders of the medial temporal lobe (MTL) adversely affect visual working memory (vWM) performance, including feature binding. It is unclear whether these impairments generalise across visual dimensions or are specifically spatial. To address this issue, we compared performance in two tasks of thirteen epilepsy patients, who had undergone a temporal lobectomy, and fifteen healthy controls. In the vWM task, participants recalled the color of one of two polygons, previously displayed side by side. At recall, a location or shape probe identified the target. In the perceptual task, participants estimated the centroid of three visible disks. Patients recalled the target color less accurately than healthy controls because they frequently swapped the non-target with the target color. Moreover, healthy controls and right temporal lobectomy patients made more swap errors following shape than space probes. Left temporal lobectomy patients, showed the opposite pattern of errors instead. Patients and controls perfor...

Loneliness is a public health concern with detrimental effects on physical and mental well-being. Given phenotypical overlaps between loneliness and social anxiety (SA), cognitive-behavioral interventions targeting SA might be adopted to reduce loneliness. However, whether SA and loneliness share the same underlying neurocognitive mechanisms is still an elusive question. The current study aimed at investigating to what extent known behavioral and neural correlates of social avoidance in SA are evident in loneliness. We used a pre-stratified approach involving 42 (21 females) participants with high loneliness (HL) and 40 (20 females) participants with low loneliness (LL) scores. During functional magnetic resonance imaging, participants completed a social gambling task to measure the subjective value of engaging in social situations and responses to social feedback. Uni- and multivariate analyses of behavioral and neural data replicated known task effects. However, although HL participants showed increased ...

Abnormal involuntary movements, or dyskinesias, are seen in many neurological diseases, including disorders where the brain appears grossly normal. This observation suggests that alterations in neural activity or connectivity may underlie dyskinesias. One influential model proposes that involuntary movements are driven by an imbalance in the activity of striatal direct and indirect pathway neurons (dMSNs and iMSNs, respectively). Indeed, in some animal models, there is evidence that dMSN hyperactivity contributes to dyskinesia. Given the many diseases associated with dyskinesia, it is unclear if these findings generalize to all forms. Here, we used male and female mice in a mouse model of paroxysmal nonkinesigenic dyskinesia (PNKD) to assess whether involuntary movements are related to aberrant activity in the striatal direct and indirect pathways. In this model, as in the human disorder PNKD, animals experience dyskinetic attacks in response to caffeine or alcohol. Using optically identified striatal sing...

Acetylcholine is an important modulator of striatal activity and it is vital to controlling striatal-dependent behaviors, including motor and cognitive functions. Despite this significance, the mechanisms determining how acetylcholine impacts striatal signaling are still not fully understood. In particular, little is known about the role of nicotinic acetylcholine receptors (nAChRs) expressed by striatal interneurons. In the present study, we used fluorescent in situ hybridization (FISH) to determine which neuronal types express the most prevalent beta2 nicotinic subunit in the mouse striatum. Our data support a common view that nAChR expression is mostly restricted to striatal interneurons. Surprisingly though, cholinergic interneurons (CINs) were identified as a population with the highest expression of beta2 nicotinic subunit. To investigate the functional significance of beta2-containing nAChRs in striatal interneurons, we deleted them by injecting the AAV-Cre vector into the striatum of beta2-flox/flo...

Calretinin (CR) is a major calcium binding protein widely expressed in the central nervous system. However, its synaptic function remains largely elusive. At the auditory synapse of the endbulb of Held, CR is selectively expressed in different subtypes. Combining electrophysiology with immunohistochemistry, we investigated the synaptic transmission at the endbulb of Held synapses with and without endogenous CR expression in mature CBA/CAJ mice of either sex. Two synapse subtypes showed similar basal synaptic transmission, except a larger quantal size in CR-expressing synapses. During high-rate stimulus trains, CR-expressing synapses showed improved synaptic efficacy with significantly less depression and lower asynchronous release, suggesting more efficient exocytosis than non-CR-expressing synapses. Conversely, CR-expressing synapses had smaller readily releasable pool size, which was countered by higher release probability and faster synaptic recovery to support sustained release during high-rate activit...

Expression and secretion of neurotrophic factors have long been known as a key mechanism of neuroglial interaction in the central nervous system. In addition, several other intrinsic neuroprotective pathways have been described, including those involving small heat shock proteins such as α-crystallins. While initially considered as a purely intracellular mechanism, both αA- and αB-crystallins have been recently reported to be secreted by glial cells. While an anti-apoptotic effect of such secreted αA-crystallin has been suggested, its regulation and protective potential remain unclear. We recently identified residue T148 and its phosphorylation as a critical regulator of αA-crystallin intrinsic neuroprotective function. In the current study, we explored how mutation of this residue affected αA-crystallin chaperone function, secretion, and paracrine protective function using primary glial and neuronal cells. After demonstrating the paracrine protective effect of αA-crystallins secreted by primary Müller gli...

The ability to separate background noise from relevant acoustic signals is essential for appropriate sound-driven behavior in natural environments. Examples of this separation are apparent in the auditory system, where neural responses to behaviorally relevant stimuli become increasingly noise-invariant along the ascending auditory pathway. However, the mechanisms that underlie this reduction in responses to background noise are not well understood. To address this gap in knowledge, we first evaluated the effects of auditory cortical inactivation on mice of both sexes trained to perform a simple auditory signal-in-noise detection task, and found that outputs from the auditory cortex are important for the detection of auditory stimuli in noisy environments. Next, we evaluated the contributions of the two most common cortical inhibitory cell types, parvalbumin-expressing (PV+) and somatostatin-expressing (SOM+) interneurons, to the perception of masked auditory stimuli. We found that inactivation of either P...