The primary motor cortex hand area (M1HAND) and adjacent dorsal premotor cortex (PMd) form the so-called motor hand knob in the precentral gyrus. M1HAND and PMd are critical for dexterous hand use and are densely interconnected via corticocortical axons, lacking a sharp demarcating border. In 24 young right-handed volunteers, we performed multimodal mapping to delineate the relationship between structure and function in the right motor hand knob. Quantitative structural magnetic resonance imaging (MRI) at 3 tesla yielded regional R1 maps as a proxy of cortical myelin content. Participants also underwent functional MRI (fMRI). We mapped task-related activation and temporal precision, while they performed a visuomotor synchronization task requiring visually cued abduction movements with the left index or little finger. We also performed sulcus-aligned transcranial magnetic stimulation of the motor hand knob to localize the optimal site (hotspot) for evoking a motor evoked potential (MEP) in two intrinsic han...

Inhibitory interneurons expressing parvalbumin (PV) are central to cortical network dynamics, generation of γ oscillations, and cognition. Dysfunction of PV interneurons disrupts cortical information processing and cognitive behavior. Brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase B (trkB) signaling regulates the maturation of cortical PV interneurons but is also implicated in their adult multidimensional functions. Using a novel viral strategy for cell-type-specific and spatially restricted expression of a dominant-negative trkB (trkB.DN), we show that BDNF/trkB signaling is essential to the integrity and maintenance of prefrontal PV interneurons in adult male and female mice. Reduced BDNF/trkB signaling in PV interneurons in the medial prefrontal cortex (mPFC) resulted in deficient PV inhibition and increased baseline local field potential (LFP) activity in a broad frequency band. The altered network activity was particularly pronounced during increased activation of the prefrontal net...

Behavioral and internal-state modulation of sensory processing has been described in several organisms. In insects, visual neurons in the optic lobe are modulated by locomotion, but the degree to which visual–motor feedback modulates these neurons remains unclear. Moreover, it also remains unknown whether self-generated and externally generated visual motion are processed differently. Here, we implemented a virtual reality system that allowed fine-scale control over visual stimulation in relation to animal motion, in combination with multichannel recording of neural activity in the medulla of a female honeybee ( Apis mellifera ). We found that this activity was modulated by locomotion, although, in most cases, only when the bee had behavioral control over the visual stimulus (i.e., in a closed-loop system). Moreover, closed-loop control modulated a third of the recorded neurons, and the application of octopamine (OA) evoked similar changes in neural responses that were observed in a closed loop. Additional...

Perceptual decision-making is increasingly being understood to involve an interaction between bottom-up sensory-driven signals and top-down choice-driven signals, but how these signals interact to mediate perception is not well understood. The parieto-insular vestibular cortex (PIVC) is an area with prominent vestibular responsiveness, and previous work has shown that inactivating PIVC impairs vestibular heading judgments. To investigate the nature of PIVC's contribution to heading perception, we recorded extracellularly from PIVC neurons in two male rhesus macaques during a heading discrimination task, and compared findings with data from previous studies of dorsal medial superior temporal (MSTd) and ventral intraparietal (VIP) areas using identical stimuli. By computing partial correlations between neural responses, heading, and choice, we find that PIVC activity reflects a dynamically changing combination of sensory and choice signals. In addition, the sensory and choice signals are more balanced in PIV...

Successful investing is challenging since stock prices are difficult to consistently forecast. Recent neuroimaging evidence suggests, however, that activity in brain regions associated with anticipatory affect may not only predict individual choice, but also forecast aggregate behavior out-of-sample. Thus, in two experiments, we specifically tested whether anticipatory affective brain activity in healthy humans could forecast aggregate changes in stock prices. Using functional magnetic resonance imaging, we found in a first experiment ( n = 34, 6 females; 140 trials/subject) that nucleus accumbens activity forecast stock price direction, whereas anterior insula (AIns) activity forecast stock price inflections. In a second preregistered replication experiment ( n = 39, 7 females) that included different subjects and stocks, AIns activity still forecast stock price inflections. Importantly, AIns activity forecast stock price movement even when choice behavior and conventional stock indicators did not (e.g., ...

Vision begins when light is captured by the outer segment organelle of photoreceptor cells in the retina. Outer segments are modified cilia filled with hundreds of flattened disk-shaped membranes. Disk membranes are separated from the surrounding plasma membrane, and each membrane type has unique protein components. The mechanisms underlying this protein sorting remain entirely unknown. In this study, we investigated the outer segment delivery of the rod cyclic nucleotide-gated (CNG) channel, which is located in the outer segment plasma membrane, where it mediates the electrical response to light. Using Xenopus and mouse models of both sexes, we now show that the targeted delivery of the CNG channel to the outer segment uses the conventional secretory pathway, including protein processing in both ER and Golgi, and requires preassembly of its constituent α1 and β1 subunits. We further demonstrate that the N-terminal glutamic acid-rich protein (GARP) domain of CNGβ1 contains two distinct functional regions. ...

Interneurons contribute to the complexity of neural circuits and maintenance of normal brain function. Rodent interneurons originate in embryonic ganglionic eminences, but developmental origins in other species are less understood. Here, we show that transcription factor expression patterns in porcine embryonic subpallium are similar to rodents, delineating a distinct medial ganglionic eminence (MGE) progenitor domain. On the basis of Nkx2.1, Lhx6, and Dlx2 expression, in vitro differentiation into neurons expressing GABA, and robust migratory capacity in explant assays, we propose that cortical and hippocampal interneurons originate from a porcine MGE region. Following xenotransplantation into adult male and female rat hippocampus, we further demonstrate that porcine MGE progenitors, like those from rodents, migrate and differentiate into morphologically distinct interneurons expressing GABA. Our findings reveal that basic rules for interneuron development are conserved across species, and that porcine em...

Hyperglycemia is a key determinant for development of diabetic retinopathy (DR). Inadequate glycemic control exacerbates retinopathy, while normalization of glucose levels delays its progression. In hyperglycemia, hexokinase is saturated and excess glucose is metabolized to sorbitol by aldose reductase via the polyol pathway. Therapies to reduce retinal polyol accumulation for the prevention of DR have been elusive because of low sorbitol dehydrogenase levels in the retina and inadequate inhibition of aldose reductase. Using systemic and conditional genetic inactivation, we targeted the primary facilitative glucose transporter in the retina, Glut1, as a preventative therapeutic in diabetic male and female mice. Unlike WT diabetics, diabetic Glut1 +/− mice did not display elevated Glut1 levels in the retina. Furthermore, diabetic Glut1 +/− mice exhibited ameliorated ERG defects, inflammation, and oxidative stress, which was correlated with a significant reduction in retinal sorbitol accumulation. Retinal pi...

Protein phosphatases, by counteracting protein kinases, regulate the reversible phosphorylation of many substrates involved in synaptic plasticity, a cellular model for learning and memory. A prominent phosphatase regulating synaptic plasticity and neurologic disorders is the serine/threonine protein phosphatase 1 (PP1). PP1 has three isoforms (α, β, and γ, encoded by three different genes), which are regulated by a vast number of interacting subunits that define their enzymatic substrate specificity. In this review, we discuss evidence showing that PP1 regulates synaptic transmission and plasticity, as well as presenting novel models of PP1 regulation suggested by recent experimental evidence. We also outline the required targeting of PP1 by neurabin and spinophilin to achieve substrate specificity at the synapse to regulate AMPAR and NMDAR function. We then highlight the role of inhibitor-2 in regulating PP1 function in plasticity, including its positive regulation of PP1 function in vivo in memory forma...