Concept: Nervous system
Mammalian sleep consists of distinct rapid eye movement (REM) and non-REM (NREM) states. The midbrain region ventrolateral periaqueductal gray (vlPAG) is known to be important for gating REM sleep, but the underlying neuronal mechanism is not well understood. Here, we show that activating vlPAG GABAergic neurons in mice suppresses the initiation and maintenance of REM sleep while consolidating NREM sleep, partly through their projection to the dorsolateral pons. Cell-type-specific recording and calcium imaging reveal that most vlPAG GABAergic neurons are strongly suppressed at REM sleep onset and activated at its termination. In addition to the rapid changes at brain state transitions, their activity decreases gradually between REM sleep and is reset by each REM episode in a duration-dependent manner, mirroring the accumulation and dissipation of REM sleep pressure. Thus, vlPAG GABAergic neurons powerfully gate REM sleep, and their firing rate modulation may contribute to the ultradian rhythm of REM/NREM alternation.
- Proceedings of the National Academy of Sciences of the United States of America
- Published about 4 years ago
The ability to acquire large-scale recordings of neuronal activity in awake and unrestrained animals is needed to provide new insights into how populations of neurons generate animal behavior. We present an instrument capable of recording intracellular calcium transients from the majority of neurons in the head of a freely behaving Caenorhabditis elegans with cellular resolution while simultaneously recording the animal’s position, posture, and locomotion. This instrument provides whole-brain imaging with cellular resolution in an unrestrained and behaving animal. We use spinning-disk confocal microscopy to capture 3D volumetric fluorescent images of neurons expressing the calcium indicator GCaMP6s at 6 head-volumes/s. A suite of three cameras monitor neuronal fluorescence and the animal’s position and orientation. Custom software tracks the 3D position of the animal’s head in real time and two feedback loops adjust a motorized stage and objective to keep the animal’s head within the field of view as the animal roams freely. We observe calcium transients from up to 77 neurons for over 4 min and correlate this activity with the animal’s behavior. We characterize noise in the system due to animal motion and show that, across worms, multiple neurons show significant correlations with modes of behavior corresponding to forward, backward, and turning locomotion.
Here, we report the existence of meningeal lymphatic vessels in human and nonhuman primates (common marmoset monkeys) and the feasibility of noninvasively imaging and mapping them in vivo with high-resolution, clinical MRI. On T2-FLAIR and T1-weighted black-blood imaging, lymphatic vessels enhance with gadobutrol, a gadolinium-based contrast agent with high propensity to extravasate across a permeable capillary endothelial barrier, but not with gadofosveset, a blood-pool contrast agent. The topography of these vessels, running alongside dural venous sinuses, recapitulates the meningeal lymphatic system of rodents. In primates, meningeal lymphatics display a typical panel of lymphatic endothelial markers by immunohistochemistry. This discovery holds promise for better understanding the normal physiology of lymphatic drainage from the central nervous system and potential aberrations in neurological diseases.
- Proceedings of the National Academy of Sciences of the United States of America
- Published almost 3 years ago
Criminal convictions require proof that a prohibited act was performed in a statutorily specified mental state. Different legal consequences, including greater punishments, are mandated for those who act in a state of knowledge, compared with a state of recklessness. Existing research, however, suggests people have trouble classifying defendants as knowing, rather than reckless, even when instructed on the relevant legal criteria. We used a machine-learning technique on brain imaging data to predict, with high accuracy, which mental state our participants were in. This predictive ability depended on both the magnitude of the risks and the amount of information about those risks possessed by the participants. Our results provide neural evidence of a detectable difference in the mental state of knowledge in contrast to recklessness and suggest, as a proof of principle, the possibility of inferring from brain data in which legally relevant category a person belongs. Some potential legal implications of this result are discussed.
The primate visual system achieves remarkable visual object recognition performance even in brief presentations, and under changes to object exemplar, geometric transformations, and background variation (a.k.a. core visual object recognition). This remarkable performance is mediated by the representation formed in inferior temporal (IT) cortex. In parallel, recent advances in machine learning have led to ever higher performing models of object recognition using artificial deep neural networks (DNNs). It remains unclear, however, whether the representational performance of DNNs rivals that of the brain. To accurately produce such a comparison, a major difficulty has been a unifying metric that accounts for experimental limitations, such as the amount of noise, the number of neural recording sites, and the number of trials, and computational limitations, such as the complexity of the decoding classifier and the number of classifier training examples. In this work, we perform a direct comparison that corrects for these experimental limitations and computational considerations. As part of our methodology, we propose an extension of “kernel analysis” that measures the generalization accuracy as a function of representational complexity. Our evaluations show that, unlike previous bio-inspired models, the latest DNNs rival the representational performance of IT cortex on this visual object recognition task. Furthermore, we show that models that perform well on measures of representational performance also perform well on measures of representational similarity to IT, and on measures of predicting individual IT multi-unit responses. Whether these DNNs rely on computational mechanisms similar to the primate visual system is yet to be determined, but, unlike all previous bio-inspired models, that possibility cannot be ruled out merely on representational performance grounds.
Neonatal abstinence syndrome (NAS) is a postnatal drug withdrawal syndrome that occurs primarily among opioid-exposed infants shortly after birth, often manifested by central nervous system irritability, autonomic overreactivity, and gastrointestinal tract dysfunction (1). During 2000-2012, the incidence of NAS in the United States significantly increased (2,3). Several recent publications have provided national estimates of NAS (2,3); however, data describing incidence at the state level are limited. CDC examined state trends in NAS incidence using all-payer, hospital inpatient delivery discharges compiled in the State Inpatient Databases of the Healthcare Cost and Utilization Project (HCUP) during 1999-2013. Among 28 states with publicly available data in HCUP during 1999-2013, the overall NAS incidence increased 300%, from 1.5 per 1,000 hospital births in 1999, to 6.0 per 1,000 hospital births in 2013. During the study period, significant increases in NAS incidence occurred in 25 of 27 states with at least 3 years of data, with annual incidence rate changes ranging from 0.05 (Hawaii) to 3.6 (Vermont) per 1,000 births. In 2013, NAS incidence ranged from 0.7 cases per 1,000 hospital births (Hawaii) to 33.4 cases per 1,000 hospital births (West Virginia). The findings underscore the importance of state-based public health programs to prevent unnecessary opioid use and to treat substance use disorders during pregnancy, as well as decrease the incidence of NAS.
Synaesthesia is a neurodevelopmental condition in which a sensation in one modality triggers a perception in a second modality. Autism (shorthand for Autism Spectrum Conditions) is a neurodevelopmental condition involving social-communication disability alongside resistance to change and unusually narrow interests or activities. Whilst on the surface they appear distinct, they have been suggested to share common atypical neural connectivity.
Many organisms spanning from bacteria to mammals orient to the earth’s magnetic field. For a few animals, central neurons responsive to earth-strength magnetic fields have been identified; however, magnetosensory neurons have yet to be identified in any animal. We show that the nematode Caenorhabditis elegans orients to the earth’s magnetic field during vertical burrowing migrations. Well-fed worms migrated up, while starved worms migrated down. Populations isolated from around the world, migrated at angles to the magnetic vector that would optimize vertical translation in their native soil, with northern- and southern-hemisphere worms displaying opposite migratory preferences. Magnetic orientation and vertical migrations required the TAX-4 cyclic nucleotide-gated ion channel in the AFD sensory neuron pair. Calcium imaging showed that these neurons respond to magnetic fields even without synaptic input. C. elegans may have adapted magnetic orientation to simplify their vertical burrowing migration by reducing the orientation task from three dimensions to one.
Patients with spinal cord injury lack the connections between brain and spinal cord circuits that are essential for voluntary movement. Clinical systems that achieve muscle contraction through functional electrical stimulation (FES) have proven to be effective in allowing patients with tetraplegia to regain control of hand movements and to achieve a greater measure of independence in daily activities. In existing clinical systems, the patient uses residual proximal limb movements to trigger pre-programmed stimulation that causes the paralysed muscles to contract, allowing use of one or two basic grasps. Instead, we have developed an FES system in primates that is controlled by recordings made from microelectrodes permanently implanted in the brain. We simulated some of the effects of the paralysis caused by C5 or C6 spinal cord injury by injecting rhesus monkeys with a local anaesthetic to block the median and ulnar nerves at the elbow. Then, using recordings from approximately 100 neurons in the motor cortex, we predicted the intended activity of several of the paralysed muscles, and used these predictions to control the intensity of stimulation of the same muscles. This process essentially bypassed the spinal cord, restoring to the monkeys voluntary control of their paralysed muscles. This achievement is a major advance towards similar restoration of hand function in human patients through brain-controlled FES. We anticipate that in human patients, this neuroprosthesis would allow much more flexible and dexterous use of the hand than is possible with existing FES systems.
Animal studies demonstrate a clear link between prenatal exposure to glucocorticoids (GC) and altered offspring brain development. We aim to examine whether prenatal GC exposure programs long-term mental health in humans.