Neural Circuity Research Articles

Photoperiodic plasticity of pigment-dispersing factor immunoreactive fibers projecting toward prothoracicotropic hormone neurons in flesh fly Sarcophaga similis larvae.

Larvae of the flesh fly, Sarcophaga similis exhibit photoperiodic responses to control pupal diapause. Although the external coincidence model is applicable to S. similis photoperiodism, it remains unknown how the circadian clock system integrates day-length information. To explore the mechanisms, we examined the neural circuitry involving circadian clock lateral neurons (LNs) and prothoracicotropic hormone (PTTH) neurons. We also examined the photoperiodic effects on LN-fiber patterns in third-instar S. similis larvae. Immunohistochemistry showed that the clock protein PERIOD and the neuropeptide pigment-dispersing factor (PDF) were co-localized in four cells per brain hemisphere, and we named these PDF-LNs of S. similis. Single-cell polymerase chain reaction of backfilled neurons from the ring gland showed that two pairs of pars lateralis neurons with contralateral axons (PL-c neurons) to the ring gland expressed ptth. Double labeling with immunohistochemistry and backfills revealed that PDF-immunoreactive varicose fibers projected close to fibers from PL-c neurons. short neuropeptide f (snpf) receptor and glutamate-gated chloride channel but not pdf receptor were expressed in PL-c neurons. sNPF and L-glutamate but not PDF acutely inhibited the spontaneous firing activity of PL-c neurons. The number of PDF-immunoreactive varicosities of PDF-LNs in the dorsal protocerebrum was significantly higher under short-day than that under long-day conditions in a time-dependent manner. These results suggest that sNPF and/or glutamate signaling to PTTH neurons and PDF-LNs form a potential neural circuity for the photoperiodic control of pupal diapause and that photoperiod modifies the connectivity strength between PDF-LNs and their post- or pre-neurons in the circuitry.

Interpersonal violence moderates sustained-transient threat co-activation in the vmPFC and amygdala in a community sample of youth.

The increased risk for psychopathology associated with interpersonal violence exposure (IPV, e.g., physical abuse, sexual assault) is partially mediated by neurobiological alterations in threat-related processes. Evidence supports parsing neural circuitry related to transient and sustained threat, as they appear to be separable processes with distinct neurobiological underpinnings. Although childhood is a sensitive period for neurodevelopment, most prior work has been conducted in adult samples. Further, it is unknown how IPV exposure may impact transient-sustained threat neural interactions. The current study tested the moderating role of IPV exposure on sustained vmPFC-transient amygdala co-activation during an fMRI task during which threat and neutral cues were predictably or unpredictably presented. Analyses were conducted in a sample of 212 community-recruited youth (M/SDage = 11.77/2.44 years old; 51.9% male; 56.1% White/Caucasian). IPV-exposed youth evidenced a positive sustained vmPFC-transient amygdala co-activation, while youth with no IPV exposure did not show this association. Consistent with theoretical models, effects were specific to unpredictable, negative trials and to exposure to IPV (i.e., unrelated to non-IPV traumatic experiences). Although preliminary, these findings provide novel insight into how childhood IPV exposure may alter neural circuity involved in specific facets of threat processing.

Combined Transcranial Direct Current Stimulation and Pain Neuroscience Education for Chronic Low Back Pain: A Randomized Controlled Trial.

Priming the neural circuity likely targeted by pain neuroscience education (PNE), using transcranial direct current stimulation (tDCS) may enhance the efficacy of PNE. The aim of this study was to compare the effects of active tDCS + PNE to sham tDCS + PNE on measures of pain, pain behaviors, and cognitive function in participants with chronic low back pain (CLBP) and high pain catastrophizing. 20 participants were recruited and randomly allocated into the active tDCS + PNE (n = 10) or sham tDCS + PNE (n = 10) groups. All participants received five sessions of their assigned interventions over a 2-week period. The active tDCS + PNE group received 20 minutes of 2 mA, anodal current applied to the left dorsolateral prefrontal cortex. Within groups, both interventions demonstrated significant improvement in NPRS, PCS, and TSK. The active tDCS + PNE group also demonstrated significant improvement on the SCWT, CTMT2-Inhibitory, and CTMT2-Set Shifting. Between groups, the active tDCS + PNE group showed significantly greater improvement on the PCS, SCWT, and CTMT2-Inhibitory. The results of this pilot study suggest that active tDCS + PNE appeared to provide greater improvement than sham tDCS + PNE on levels of pain catastrophizing and attentional interference in participants with CLBP and high pain catastrophizing, consistent with both interventions targeting brain regions involved in those processes. Considering the differences between groups, tDCS appears to provide a priming effect on PNE.

Can targeting TSP-1 with gabapentin enhance survival in glioblastoma? A 20-year retrospective cohort study.

2048 Background: Molecularly-defined cellular subpopulations of glioblastoma secrete high levels of the synaptogenic protein thrombospondin-1 (TSP-1) which promotes functional integration of tumor into neural circuity. A greater extent of glioma-neuronal crosstalk portends worse survival for patients. In preclinical studies, gabapentin was shown to inhibit TSP-1, in turn disrupting neuronal synaptogenesis and neuronal activity-dependent glioblastoma proliferation; however, clinical survival data is lacking. We aim to determine whether treatment with gabapentin is associated with improved survival and reduced serum TSP-1 in a retrospective cohort of patients with IDH-wildtype glioblastoma. Methods: Newly-diagnosed, IDH-wildtype glioblastoma patients who received care at the UCSF Brain Tumor Center between 1997-2017 were included in this study. Kaplan-Meier curves and multivariate Cox proportional-hazards models, controlled for age, MGMT promoter methylation status, preoperative tumor volume, and extent of resection, were used for survival analyses. Differences in serum TSP-1 measured by ELISA for gabapentin treated patients and matched non-gabapentin treated controls were assessed using unpaired two-tailed student’s t-test. Control samples were matched 2:1 by age, tumor volume, and extent of resection. After 2005, patients were treated with chemoradiation with concurrent and adjuvant temodar. Results: Among 379 adult patients with glioblastoma, 36 (9.5%) were treated with gabapentin. The median daily dose of gabapentin was 600 mg (IQR: 300-900 mg). There were no significant differences between gabapentin treated and non-gabapentin treated patients by age (0.06), sex (p=0.14), or race (p=0.52). Median overall survival for gabapentin treated and non-gabapentin treated patients was 20.8 months (IQR: 11.7 - 32.1) and 14.7 months (IQR: 8.9-23.5), respectively (p= 0.02). On Kaplan-Meier survival analysis, overall survival was longer for gabapentin treated patients compared with non-gabapentin treated patients (p=0.005). In the multivariate Cox proportional-hazards model, gabapentin use was associated with decreased hazard of death (HR 0.67, p=0.030). Mean serum TSP-1 in gabapentin-treated patients was significantly lower than in the matched control group (10181 ng/ml vs 17015 ng/ml, p=0.017). Conclusions: Gabapentin use is associated with a survival benefit for patients with glioblastoma, possibly mediated through a reduction in TSP-1. This promising result lays the foundation for future prospective studies to further evaluate TSP-1 as a circulating prognostic biomarker as well as to explore the therapeutic benefits of gabapentin as a life-prolonging treatment for patients with newly diagnosed glioblastoma.

Interspecies chimerism with human embryonic stem cells generates functional human dopamine neurons at low efficiency

Interspecies chimeras offer great potential for regenerative medicine and the creation of human disease models. Whether human pluripotent stem cell-derived neurons in an interspecies chimera can differentiate into functional neurons and integrate into host neural circuity is not known. Here, we show, using Engrailed 1 (En1) as a development niche, that human naive-like embryonic stem cells (ESCs) can incorporate into embryonic and adult mouse brains. Human-derived neurons including tyrosine hydroxylase (TH)+ neurons integrate into the mouse brain at low efficiency. These TH+ neurons have electrophysiologic properties consistent with their human origin. In addition, these human-derived neurons in the mouse brain accumulate pathologic phosphorylated α-synuclein in response to α-synuclein preformed fibrils. Optimization of human/mouse chimeras could be used to study human neuronal differentiation and human brain disorders.

Deep brain stimulation (DBS) may hold substantial promise for modulating memory and neural circuity in AD?

Deep brain stimulation (DBS) may hold substantial promise for modulating memory and neural circuity in AD?

A neural pathway underlying hunger modulation of sexual receptivity in Drosophila females

Accepting or rejecting a mate is one of the most crucial decisions a female will make, especially when faced with food shortage. Previous studies have identified the core neural circuity from sensing male courtship or mating status to decision-making for sexual receptivity in Drosophila females, but how hunger and satiety states modulate female receptivity is poorly understood. Here, we identify the neural circuit and its neuromodulation underlying the hunger modulation of female receptivity. We find that adipokinetic hormone receptor (AkhR)-expressing neurons inhibit sexual receptivity in a starvation-dependent manner. AkhR neurons are octopaminergic and act on a subset of Octβ1R-expressing LH421 neurons. Knocking down Octβ1R expression in LH421 neurons eliminates starvation-induced suppression of female receptivity. We further find that LH421 neurons inhibit the sex-promoting pC1 neurons via GABA-resistant to dieldrin (Rdl) signaling. pC1 neurons also integrate courtship stimulation and mating status and thus serve as a common integrator of multiple internal and external cues for decision-making.

Incorporating Auditory Cortex Potentials and Gap Pre-pulse Inhibition of Acoustic Startle: A Probable Way to Objectively Assess Tinnitus

Background and Objectives: Tinnitus is a complex condition that varies in loudness, quality, location, and distress. Different definitions, heterogeneity, and lack of objective measuring have challenged the understanding the mechanisms involved and definitive cure. The integrative model correlates each of these characteristics to separate parallel and overlapping subnetworks that process tinnitus’s perception and emotional reaction. Many of these networks are common with the gap pre-pulse inhibition of acoustic startle (GPIAS) neural circuity. GPIAS, which measures tinnitus in animals, has recently been used for humans with various recording methods. The present study aimed to review the evidence achieved with gap stimuli in patients with tinnitus to support the potential of cortical responses recorded with the GPIAS stimulus and to objectively detect tinnitus in humans. Methods: Studies were identified by searching electronic databases with relevant keywords. Results: The role of the auditory cortex in processing short gaps, the possibility of evaluating the gap detection ability with GPIAS, and the advantage of cortical responses in reflecting both stimulus properties and different aspects of tinnitus emphasize the importance of this issue. The results of most studies have proven the gap detection deficiency in tinnitus. However, the validity of the auditory startle reflex still needs to be verified due to the inherent variability and different methods. Conclusion: Further human studies are recommended because the perception of tinnitus can be controlled. An appealing research line in this area is multi-channel cortical evoked potentials. Defects of GPIAS with cortical recording can indicate tinnitus.

Identification of a Glutamatergic Claustrum-Anterior Cingulate Cortex Circuit for Visceral Pain Processing.

Chronic visceral pain is a major challenge for both patients and health providers. Although the central sensitization of the brain is thought to play an important role in the development of visceral pain, the detailed neural circuits remain largely unknown. Using a well-established chronic visceral hypersensitivity model induced by neonatal maternal deprivation (NMD) in male mice, we identified a distinct pathway whereby the claustrum (CL) glutamatergic neuron projecting to the anterior cingulate cortex (ACC) is critical for visceral pain but not for CFA-evoked inflammatory pain. By a combination of in vivo circuit-dissecting extracellular electrophysiological approaches and visceral pain related electromyographic (EMG) recordings, we demonstrated that optogenetic inhibition of CL glutamatergic activity suppressed the ACC neural activity and visceral hypersensitivity of NMD mice whereas selective activation of CL glutamatergic activity enhanced the ACC neural activity and evoked visceral pain of control mice. Further, optogenetic studies demonstrate a causal link between such neuronal activity and visceral pain behaviors. Chemogenetic activation or inhibition of ACC neural activities reversed the effects of optogenetic manipulation of CL neural activities on visceral pain responses. Importantly, molecular detection showed that NMD significantly enhances the expression of NMDA receptors and activated CaMKIIα in the ACC postsynaptic density (PSD) region. Together, our data establish a functional role for CL→ACC glutamatergic neurons in gating visceral pain, thus providing a potential treatment strategy for visceral pain.SIGNIFICANCE STATEMENT Studies have shown that sensitization of anterior cingulate cortex (ACC) plays an important role in chronic pain. However, it is as yet unknown whether there is a specific brain region and a distinct neural circuit that helps the ACC to distinguish visceral and somatic pain. The present study demonstrates that claustrum (CL) glutamatergic neurons maybe responding to colorectal distention (CRD) rather than somatic stimulation and that a CL glutamatergic projection to ACC glutamatergic neuron regulates visceral pain in mice. Furthermore, excessive NMDA receptors and overactive CaMKIIα in the ACC postsynaptic density (PSD) region were observed in mice with chronic visceral pain. Together, these findings reveal a novel neural circuity underlying the central sensitization of chronic visceral pain.

Functional Neuroimaging of Human Hypothalamus in Socioemotional Behavior: A Systematic Review.

There exist extensive animal research and lesion studies in humans demonstrating a tight association between the hypothalamus and socioemotional behavior. However, human neuroimaging literature in this direction is still rather limited. In order to reexamine the functional role of this region in regulating human social behavior, we here provided a synthesis of neuroimaging studies showing hypothalamic activation during affiliative, cooperative interactions, and in relation to ticklish laughter and humor. In addition, studies reporting involvement of the hypothalamus during aggressive and antisocial interactions were also considered. Our systematic review revealed a growing number of investigations demonstrating that the evolutionary conserved hypothalamic neural circuity is involved in multiple and diverse aspects of human socioemotional behavior. On the basis of the observed heterogeneity of hypothalamus-mediated socioemotional responses, we concluded that the hypothalamus might play an extended functional role for species survival and preservation, ranging from exploratory and approaching behaviors promoting social interactions to aggressive and avoidance responses protecting and defending the established social bonds.

The yellow gene regulates behavioural plasticity by repressing male courtship in Bicyclus anynana butterflies.

Seasonal plasticity in male courtship in Bicyclus anynana butterflies is due to variation in levels of the steroid hormone 20E (20-hydroxyecdysone) during pupation. Wet season (WS) males have high levels of 20E and become active courters. Dry season (DS) males have lower levels of 20E and reduced courtship rates. However, WS courtship rates can be achieved if DS male pupae are injected with 20E at 30% of pupation. Here, we investigated the genes involved in male courtship plasticity and examined whether 20E plays an organizational role in the pupal brain that later influences the sexual behaviour of adults. We show that DS pupal brains have a sevenfold upregulation of the yellow gene relative to the WS brains, and that knocking out yellow leads to increased male courtship. We find that injecting 20E into DS pupa reduced yellow expression although not significantly. Our results show that yellow is a repressor of the neural circuity for male courtship behaviour in B. anynana. 20E levels experienced during pupation could play an organizational role during pupal brain development by regulating yellow expression, however, other factors might also be involved. Our findings are in striking contrast to Drosophila where yellow is required for male courtship.

Does the Application of Deep Brain Stimulation to Modulate Memory and Neural Circuity in AD Hold Substantial Promise?

Does the Application of Deep Brain Stimulation to Modulate Memory and Neural Circuity in AD Hold Substantial Promise?

Adolescent stress experience–expression–physiology correspondence: Links to depression, self-injurious thoughts and behaviors, and frontolimbic neural circuity

BackgroundDysregulated stress responsivity is implicated in adolescent risk for depression and self-injurious thoughts and behaviors (STBs). However, studies often examine levels of the stress response in isolation, precluding understanding of how coordinated disturbance across systems confers risk. The current study utilized a novel person-centered approach to identify stress correspondence profiles and linked them to depressive symptoms, STBs, and neural indices of self-regulatory capacity. MethodAdolescents with and without a major depressive disorder diagnosis (N = 162, Mage = 16.54, SD = 1.96, 72.8% White, 66.5% female) completed the Trier Social Stress Test (TSST), questionnaires, and clinical interviews. Stress experience (self-report), expression (observed), and physiology (salivary cortisol) were assessed during the experimental protocol. Adolescents also underwent a magnetic resonance imaging scan. ResultsMultitrajectory modeling revealed four profiles. High Experience–High Expression–Low Physiology (i.e., lower stress correspondence) adolescents were more likely to report depressive symptoms, lifetime nonsuicidal self-injury, and suicidal ideation relative to all other subgroups reflecting higher stress correspondence: Low Experience–Low Expression–Low Physiology, Moderate Experience–Moderate Expression–Moderate Physiology, High Experience–High Expression–High Physiology. High Experience–High Expression–Low Physiology adolescents also exhibited less positive amygdala–ventromedial prefrontal cortex resting state functional connectivity relative to Moderate Experience–Moderate Expression–Moderate Physiology. LimitationsData were cross-sectional, precluding inference about our profiles as etiological risk factors or mechanisms of risk. ConclusionsFindings illustrate meaningful heterogeneity in adolescent stress correspondence with implications for multimodal, multilevel assessment and outcome monitoring in depression prevention and intervention efforts.

Functional selectivity for social interaction perception in the human superior temporal sulcus during natural viewing

Recognizing others’ social interactions is a crucial human ability. Using simple stimuli, previous studies have shown that social interactions are selectively processed in the superior temporal sulcus (STS), but prior work with movies has suggested that social interactions are processed in the medial prefrontal cortex (mPFC), part of the theory of mind network. It remains unknown to what extent social interaction selectivity is observed in real world stimuli when controlling for other covarying perceptual and social information, such as faces, voices, and theory of mind. The current study utilizes a functional magnetic resonance imaging (fMRI) movie paradigm and advanced machine learning methods to uncover the brain mechanisms uniquely underlying naturalistic social interaction perception. We analyzed two publicly available fMRI datasets, collected while both male and female human participants (n = 17 and 18) watched two different commercial movies in the MRI scanner. By performing voxel-wise encoding and variance partitioning analyses, we found that broad social-affective features predict neural responses in social brain regions, including the STS and mPFC. However, only the STS showed robust and unique selectivity specifically to social interactions, independent from other covarying features. This selectivity was observed across two separate fMRI datasets. These findings suggest that naturalistic social interaction perception recruits dedicated neural circuity in the STS, separate from the theory of mind network, and is a critical dimension of human social understanding.

Mobile Electroencephalography for Studying Neural Control of Human Locomotion.

Walking or running in real-world environments requires dynamic multisensory processing within the brain. Studying supraspinal neural pathways during human locomotion provides opportunities to better understand complex neural circuity that may become compromised due to aging, neurological disorder, or disease. Knowledge gained from studies examining human electrical brain dynamics during gait can also lay foundations for developing locomotor neurotechnologies for rehabilitation or human performance. Technical barriers have largely prohibited neuroimaging during gait, but the portability and precise temporal resolution of non-invasive electroencephalography (EEG) have expanded human neuromotor research into increasingly dynamic tasks. In this narrative mini-review, we provide a (1) brief introduction and overview of modern neuroimaging technologies and then identify considerations for (2) mobile EEG hardware, (3) and data processing, (4) including technical challenges and possible solutions. Finally, we summarize (5) knowledge gained from human locomotor control studies that have used mobile EEG, and (6) discuss future directions for real-world neuroimaging research.

Mapping the Microstructure and Striae of the Human Olfactory Tract with Diffusion MRI.

The human sense of smell plays an important role in appetite and food intake, detecting environmental threats, social interactions, and memory processing. However, little is known about the neural circuity supporting its function. The olfactory tracts project from the olfactory bulb along the base of the frontal cortex, branching into several striae to meet diverse cortical regions. Historically, using diffusion magnetic resonance imaging (dMRI) to reconstruct the human olfactory tracts has been prevented by susceptibility and motion artifacts. Here, we used a dMRI method with readout segmentation of long variable echo-trains (RESOLVE) to minimize image distortions and characterize the human olfactory tracts in vivo. We collected high-resolution dMRI data from 25 healthy human participants (12 male and 13 female) and performed probabilistic tractography using constrained spherical deconvolution (CSD). At the individual subject level, we identified the lateral, medial, and intermediate striae with their respective cortical connections to the piriform cortex and amygdala (AMY), olfactory tubercle (OT), and anterior olfactory nucleus (AON). We combined individual results across subjects to create a normalized, probabilistic atlas of the olfactory tracts. We then investigated the relationship between olfactory perceptual scores and measures of white matter integrity, including mean diffusivity (MD). Importantly, we found that olfactory tract MD negatively correlated with odor discrimination performance. In summary, our results provide a detailed characterization of the connectivity of the human olfactory tracts and demonstrate an association between their structural integrity and olfactory perceptual function.SIGNIFICANCE STATEMENT This study provides the first detailed in vivo description of the cortical connectivity of the three olfactory tract striae in the human brain, using diffusion magnetic resonance imaging (dMRI). Additionally, we show that tract microstructure correlates with performance on an odor discrimination task, suggesting a link between the structural integrity of the olfactory tracts and odor perception. Lastly, we generated a normalized probabilistic atlas of the olfactory tracts that may be used in future research to study its integrity in health and disease.

A Multisensory Deficit in the Perception of Pleasantness in Parkinson's Disease.

There is growing interest in non-motor symptoms in Parkinson's disease (PD), due to the impact on quality of life. Anhedonia, the inability to experience joy and lust, has a prevalence of up to 46% in PD. The perception of pleasantness of an odor is reduced in anhedonia without PD. We previously showed a reduced hedonic olfactory perception in PD, i.e., patients evaluated odors as less pleasant or unpleasant compared to controls. This deficit correlated with anhedonia. We aimed to confirm these findings. Moreover, we hypothesized that the perception of pleasantness in PD is affected on a multisensory level and correlates with anhedonia. Therefore, we assessed olfactory, visual and acoustic evaluation of pleasantness in PD and healthy individuals. Participants had to rate the pleasantness of 22 odors, pictures, and sounds on a nine-point Likert scale. Depression, anhedonia, and apathy were assessed by means of questionnaires. Results of the pleasantness-rating were compared between groups and correlated to scores of the questionnaires. In particular pleasant and unpleasant stimuli across all three modalities are perceived less intense in PD, suggesting that a reduced range of perception of pleasantness is a multisensory phenomenon. However, only a reduction of visual hedonic perception correlated with anhedonia in PD. A correlation of reduced perception of pleasantness with apathy or depression was not present. We provide evidence for a multisensory deficit in the perception of pleasantness. Further studies should delineate the underlying neural circuity and the diagnostic value to detect neuropsychiatric symptoms in PD.

Trace Amine‐Associated Receptor Intracellular Localization and Trafficking

Trace amine-associated receptor 1 (TAAR1) is a G-protein coupled receptor (GPCR) found in monoaminergic neurons of the central nervous system. Amphetamine-like psychostimulants activate TAAR1, which couples to Gαs and Gα13 downstream signaling cascades, and the latter regulates the RhoA-mediated internalization of neurotransmitter transporters. TAAR1 stimulation is crucial to methamphetamine (MA) mechanism of action, and a common variant of TAAR1 is associated with increased MA craving in MA users. Although the impact of TAAR1 on behavior has been characterized, the molecular mechanisms underlying TAAR1 pharmacology are incompletely understood. TAAR1 is a unique GPCR as it resides inside the cell rather than at the cell surface, though the precise location of TAAR1 within the cell is unknown. Understanding the intracellular localization, orientation, and trafficking of TAAR1 will further inform the molecular mechanisms of TAAR1 signaling. However, available antibodies and fluorescent fusion proteins for imaging TAAR1 are inadequate for such studies. Therefore, we have developed a novel method for imaging human TAAR1 (hTAAR1) through both light and electron microscopy using the miniVIPER peptide labeling system for multiscale microscopy. The hTAAR1-miniVIPER system has been applied to in vitro systems and has been used in conjunction with light microscopy to explore subcellular localization of the recombinant receptor in Chinese hamster ovary cells. Further investigation with electron microscopy will be carried out to determine the orientation of hTAAR1 on internal membranes and will indicate how TAAR1 mobilizes spatially distinct signaling cascades within the cell. In order to study the receptor in native tissue, AAV constructs will be employed to express the hTAAR1-miniVIPER construct in the dopamine neurons of mice. Tissue from these animals will be imaged through correlative light and electron microscopy to determine the subcellular localization and orientation of TAAR1. Animals expressing hTAAR1-miniR will be subjected to acute and chronic drug treatments to determine how TAAR1 agonism affects receptor localization and trafficking. Together these studies will expand our current understanding of molecular mechanisms of TAAR1 signaling and will inform future work concerning the role TAAR1 plays in the modulation of neural circuity relevant to addiction and methamphetamine use disorder.

Neuroligin-1-Modified Electrodes for Specific Coupling with a Presynaptic Neuronal Membrane.

Coordination of synapses onto electrodes with high specificity and maintaining a stable and long-lasting interface have importance in the field of neural interfaces. One potential approach is to present ligands on the surface of electrodes that would be bound through a protein-protein interaction to specific areas of neuronal cells. Here, we functionalize electrode surfaces with genetically engineered neuroligin-1 protein and demonstrate the formation of a nascent presynaptic bouton upon binding to neurexin-1 β on the presynaptic membrane of neurons. The resulting synaptically connected electrode shows an assembly of presynaptic proteins and comparable exocytosis kinetics to that of native synapses. Importantly, a neuroligin-1-induced synapse-electrode interface exhibits type specificity and structural robustness. We envision that the use of synaptic adhesion proteins in modified neural electrodes may lead to new approaches in the interfacing of neural circuity and electronics.

The neurocognitive basis of skilled reading in prelingually and profoundly deaf adults.

Deaf individuals have unique sensory and linguistic experiences that influence how they read and become skilled readers. This review presents our current understanding of the neurocognitive underpinnings of reading skill in deaf adults. Key behavioural and neuroimaging studies are integrated to build a profile of skilled adult deaf readers and to examine how changes in visual attention and reduced access to auditory input and phonology shape how they read both words and sentences. Crucially, the behaviours, processes, and neural circuity of deaf readers are compared to those of hearing readers with similar reading ability to help identify alternative pathways to reading success. Overall, sensitivity to orthographic and semantic information is comparable for skilled deaf and hearing readers, but deaf readers rely less on phonology and show greater engagement of the right hemisphere in visual word processing. During sentence reading, deaf readers process visual word forms more efficiently and may have a greater reliance on and altered connectivity to semantic information compared to their hearing peers. These findings highlight the plasticity of the reading system and point to alternative pathways to reading success.