Extinguishing the previously acquired fear is critical for organism’s adaptation to the ever-changing environment, a process requiring the engagement of GABAA receptors (GABAARs). GABAARs consist of tens of structurally, pharmacologically and functionally heterogeneous subtypes. However, the specific roles of these subtypes in fear extinction remain largely unexplored. Here, we observed that in the medial prefrontal cortex (mPFC), a core region for mood regulation, the extrasynaptically-situated, δ subunit-containing GABAARs (GABAA(δ)Rs), had a permissive role in tuning fear extinction in male mice, an effect sharply contrasting to the established but suppressive role by the whole GABAAR family. First, the fear extinction in individual mice was positively correlated with the level of GABAA(δ)R expression and function in their mPFC. Second, knockdown of GABAA(δ)R in mPFC, specifically in its infralimbic subregion (IL), sufficed to impair the fear extinction in mice. Third, GABAA(δ)R-deficient mice also show...

Adolescence is characterized by the maturation of cortical microstructure and connectivity supporting complex cognition and behavior. Axonal myelination influences brain connectivity during development by enhancing neural signaling speed and inhibiting plasticity. However, the maturational timing of cortical myelination during human adolescence remains poorly understood. Here, we take advantage of recent advances in high-resolution cortical T1w/T2w mapping methods, including principled correction of B1+ transmit field effects, using data from the Human Connectome Project in Development (N=628, ages 8-21). We characterize microstructural changes relevant to myelination by estimating age-related differences in T1w/T2w throughout the cerebral neocortex from childhood to early adulthood. We apply Bayesian spline models and clustering analysis to demonstrate graded variation in age-dependent cortical T1w/T2w differences that are correlated with the sensorimotor-association (S-A) axis of cortical organization re...

Despite ample behavioral evidence of atypical facial emotion processing in individuals with autism spectrum disorder (ASD), the neural underpinnings of such behavioral heterogeneities remain unclear. Here, I have used brain-tissue mapped artificial neural network (ANN) models of primate vision to probe candidate neural and behavior markers of atypical facial emotion recognition in ASD at an image-by-image level. Interestingly, the ANNs' image-level behavioral patterns better matched the neurotypical subjects' behavior than those measured in ASD. This behavioral mismatch was most remarkable when the ANN behavior was decoded from units that correspond to the primate inferior temporal (IT) cortex. ANN-IT responses also explained a significant fraction of the image-level behavioral predictivity associated with neural activity in the human amygdala (from epileptic patients without ASD)— strongly suggesting that the previously reported facial emotion intensity encodes in the human amygdala could be primarily dri...

GABAergic inhibitory neurons, through their molecular, anatomic, and physiological diversity, provide a substrate for the modulation of ongoing cortical circuit activity throughout the sleep/wake cycle. Here, we investigated neuronal activity dynamics of parvalbumin (PV), vasoactive intestinal polypeptide (VIP), and somatostatin (SST) neurons in naturally sleeping head-restrained mice at the level of layer 2/3 of the primary somatosensory barrel cortex of mice. Through calcium imaging and targeted single-unit loose-patch or whole-cell recordings, we found that PV action potential firing activity was largest during both rapid eye movement (REM) and nonrapid eye movement (NREM) sleep stages, that VIP neurons were most active during REM sleep, and that the overall activity of SST neurons remained stable throughout the sleep/wake cycle. Analysis of neuronal activity dynamics uncovered rapid decreases in PV cell firing at wake onset followed by a progressive recovery during wake. Simultaneous local field potent...

At the request of the authors, The Journal of Neuroscience is retracting “Tracking Age Differences in Neural Distinctiveness across Representational Levels,” by Malte Kobelt, Verena R. Sommer, Attila Keresztes, Markus Werkle-Bergner, and Myriam C. Sander, which appeared on pages [3499–3511][1

The predisposition to engage in autonomous habitual behaviors has been associated with behavioral disorders, such as obsessive-compulsive disorder and addiction. Attentional set-shifting tasks (ASSTs), which incorporate changes governing the association of discriminative stimuli with contingent reinforcement, are commonly used to measure underlying processes of cognitive/behavioral flexibility. The purpose of this study was to identify primate brain networks that mediate trait-like deficits in ASST performance using resting-state fMRI. A self-pacing ASST was administered to three cohorts of rhesus monkeys (total n = 35, 18 female). Increased performance over 30 consecutive sessions segregated the monkeys into two populations, termed High Performers (HP, n = 17) and Low Performers (LP, n = 17), with one anomaly. Compared with LPs, HPs had higher rates of improving performance over sessions and completed the 8 sets/sessions with fewer errors. LP monkeys, on the other hand, spent most of each session in the f...

Normal neural circuits and functions depend on proper neuronal differentiation, migration, synaptic plasticity, and maintenance. Abnormalities in these processes underlie various neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Neural development and maintenance are regulated by many proteins. Among them are Par3, Par6 (partitioning defective 3 and 6), and aPKC (atypical protein kinase C) families of evolutionarily conserved polarity proteins. These proteins perform versatile functions by forming tripartite or other combinations of protein complexes, which hereafter are collectively referred to as “Par complexes.” In this review, we summarize the major findings on their biophysical and biochemical properties in cell polarization and signaling pathways. We next summarize their expression and localization in the nervous system as well as their versatile functions in various aspects of neurodevelopment, including neuroepithelial polarity, neurogenesis, neuronal migration, neurite differe...

Women have been contributing to the field of neuroscience since its inception, but their accomplishments are often overlooked. Lack of recognition, among other issues, has led to progressively fewer women at each academic stage; although half of neuroscience graduate students are women, women comprise less than one-third of neuroscience faculty, and even fewer full professors. Those who reach this level continue to struggle to get their work recognized. Women from historically excluded backgrounds are even more starkly underrepresented and face added challenges related to racial, ethnic, and other biases. To increase the visibility of women in neuroscience, promote their voices, and learn about their career journeys, we created Stories of Women in Neuroscience (Stories of WiN). Stories of WiN shares the scientific and personal stories of women neuroscientists with diverse backgrounds, identities, research interests, and at various career stages. From >70 women highlighted thus far, a major theme has emerge...

Neuronal excitability relies on coordinated action of functionally distinction channels. Voltage-gated sodium (NaV) and potassium (KV) channels have distinct but complementary roles in firing action potentials: NaV channels provide depolarizing current while KV channels provide hyperpolarizing current. Mutations and dysfunction of multiple NaV and KV channels underlie disorders of excitability, including pain and epilepsy. Modulating ion channel trafficking may offer a potential therapeutic strategy for these diseases. A fundamental question, however, is whether these channels with distinct functional roles are transported independently or packaged together in the same vesicles in sensory axons. We have used Optical Pulse-Chase Axonal Long-distance imaging to investigate trafficking of NaV and KV channels and other axonal proteins from distinct functional classes in live rodent sensory neurons (from male and female rats). We show that, similar to NaV1.7 channels, NaV1.8 and KV7.2 channels are transported i...

Our ability to effectively retrieve complex semantic knowledge meaningfully impacts our daily lives, yet the neural processes that underly successful access and transient failures in access remain only partially understood. In this fMRI study, we contrast activation during successful semantic access, unsuccessful semantic access because of transient access failures (i.e., “tip-of-the-tongue,” “feeling-of-knowing”), and trials where the semantic knowledge was not possessed. Twenty-four human participants (14 female) were presented 240 trivia-based questions relating to person, place, object, or scholastic knowledge domains. Analyses of the recall event indicated a relatively greater role of a dorsomedial section of the prefrontal cortex in unsuccessful semantic access and relatively greater recruitment of the pars orbitalis of the inferior frontal gyrus in successful access. Successful access was also associated with increased activation in knowledge domain-selective areas. Generally, knowledge domain-selec...