Category learning, learning to sort a set of stimuli into categories or groups, can induce category biases in perception such that items in the same category are perceived as more similar than items from different categories. To what degree category bias develops when learning goals emphasize individuation of each stimulus and whether the bias emerges spontaneously during learning itself rather than in response to task demands is unclear. Here, we used functional MRI (fMRI) during encoding to test for category biases in neural representations of individual stimuli during learning. Human participants (males and females) encountered face-blend stimuli with unique first names and shared family names that indicated category membership. Participants were instructed to learn the full name for each face. Neural pattern classification and pattern similarity analyses were used to track category information in the brain. Results showed that stimulus category could be decoded during encoding across many frontal, pari...

We previously reported that ADAM17 is a key protease regulating myelin formation. We now describe a role for ADAM17 during the Wallerian degeneration process. Unexpectedly, we observed that glial ADAM17, by regulating p75NTR processing, cell autonomously promotes remyelination, while neuronal ADAM17 is dispensable. Accordingly, p75NTR abnormally accumulates specifically when ADAM17 is maximally expressed leading to a down–regulation of tPA expression, excessive fibrin accumulation over time and delayed remyelination. Mutant mice also present impaired macrophage recruitment and defective nerve conduction velocity. Thus, ADAM17 expressed in Schwann cells, controls the whole Wallerian degeneration process and its absence hampers effective nerve repair. Collectively, we describe a previously uncharacterized role for glial ADAM17 during nerve regeneration. Based on the results of our study, we posit that, unlike development, glial ADAM17 promotes remyelination through the regulation of p75NTR –mediated fibrinol...

Patricia L. Murphy, Jesse Isaacman-Beck, and Michael Granato (see pages [762–776][1]) Unlike CNS axons, peripheral nerves can regenerate and reinnervate their targets after injury. This requires axons to navigate through an environment that has changed substantially since the axons' initial

Group I mGluRs have diverse functions in some fundamental neuronal processes, including modulation of synaptic plasticity; and dysregulation of these receptors could lead to various neuropsychiatric disorders. Trafficking of Group I mGluRs plays critical roles in controlling the precise spatiotemporal localization and activity of these receptors, both of which contribute to proper downstream signaling. Using “molecular replacement” approach in hippocampal neurons derived from mice of both sexes, we demonstrate a critical role for the postsynaptic density protein Norbin in regulating the ligand-induced internalization of Group I mGluRs. We show that Norbin associates with protein kinase A (PKA) through its N-terminus and anchors mGluR5 through its C-terminus, both of which are necessary for the ligand-mediated endocytosis of mGluR5, a member of the Group I mGluR family. A point mutation (A687G) at the C-terminus of Norbin inhibits the binding of Norbin to mGluR5 and blocks mGluR5 endocytosis. Finally, we de...

Taste buds contain multiple cell types, two of which mediate transduction of specific taste qualities: Type III cells transduce sour while Type II cells transduce either sweet, or bitter or umami. In order to discern the degree of interaction between different cell types and specificity of connectivity with the afferent nerve fibers (NFs), we employed serial blockface scanning electron microscopy (sbfSEM) through five circumvallate mouse taste buds. Points of contact between Type II and Type III cells are rare and lack morphologically identifiable synapses, suggesting that interaction between these cell types does not occur via synapses. Of the 127 NFs that make synaptic contacts with taste cells in the sampling volume, ∼70% ( n = 91) synapse with only one taste cell while 32 fibers synapse exclusively with multiple Type II cells or multiple Type III cells. Our data do not rule out multimodal fibers innervating Type II cells of separate taste qualities. Notably, four fibers (∼3%) synapse with both Type II ...

Chemical communication controls a wide range of behaviors via conserved signaling networks. Axon regeneration in response to injury is determined by the interaction between the extracellular environment and intrinsic growth potential. In this study, we investigated the role of chemical signaling in axon regeneration in Caenorhabditis elegans . We find that the enzymes involved in ascaroside pheromone biosynthesis, ACOX-1.1, ACOX-1.2, and DAF-22, participate in axon regeneration by producing a dauer-inducing ascaroside, ascr#5. We demonstrate that the chemoreceptor genes, srg-36 and srg-37 , which encode G-protein-coupled receptors for ascr#5, are required for adult-specific axon regeneration. Furthermore, the activating mutation in egl-30 encoding Gqα suppresses axon regeneration defective phenotype in acox-1.1 and srg-36 srg-37 mutants. Therefore, the ascaroside signaling system provides a unique example of a signaling molecule that regulates the regenerative pathway in the nervous system. SIGNIFICANCE S...

The capacity to suppress learned responses is essential for animals to adapt in dynamic environments. Extinction is a process by which animals learn to suppress conditioned responding when an expected outcome is omitted. The infralimbic (IL) cortex to nucleus accumbens shell (NAcS) neural circuit is implicated in suppressing conditioned responding after extinction, especially in the context of operant cocaine-seeking behavior. However, the role of the IL-to-NAcS neural circuit in the extinction of responding to appetitive Pavlovian cues is unknown, and the psychological mechanisms involved in response suppression following extinction are unclear. We trained male Long Evans rats to associate a 10 s auditory conditioned stimulus (CS; 14 trials per session) with a sucrose unconditioned stimulus (US; 0.2 ml per CS) in a specific context, and then following extinction in a different context, precipitated a renewal of CS responding by presenting the CS alone in the original Pavlovian conditioning context. Unilat...

The understanding of the electrophysiological properties of the subthalamic nucleus (STN) neurons is crucial since it represents the main target of deep brain stimulation for the treatment of Parkinson’s Disease and obsessive compulsive disorders. The study of its non-motor properties could shed light on the cognitive and motivational alterations possibly encountered after stimulation. In this study, we recorded the activity of STN neurons in two male behaving monkeys ( Macaca mulatta ) while they performed a visuomotor motivational task in which visual cues indicated which amount of force was required to obtain which amount of reward. Our results evidenced force- and reward-modulated neurons. After the occurrence of the visual stimuli, the force-modulated neurons mainly fired when a high effort was required. Differently, the activity of the population of reward-modulated neurons encoded the motivational value of the stimuli. This population consisted of neurons increasing or decreasing their activity acco...

Repetitive mild traumatic brain injury (mTBI) in children and adolescents leads to acute and chronic neurological sequelae and is linked to later life neurodegenerative disease. However, the biological mechanisms connecting early life mTBI to neurodegeneration remain unknown. Using an adolescent mouse repetitive closed head injury (CHI) model that induces progressive cognitive impairment in males and anxiety in females in the absence of overt histopathology, we examined transcriptional and translational changes in neurons isolated from sham and injured brain in the chronic phase after injury. At 14 months, single-nuclei RNA sequencing of cortical brain tissue identified disruption of genes associated with neuronal proteostasis and evidence for disrupted ligand-receptor signaling networks in injured mice. Western blot analysis of isolated neurons showed evidence of inflammasome activation and downstream interleukin-1 beta (IL-1β) processing, as previously demonstrated in acute central nervous system injury ...