Detection thresholds of macaque otolith afferents

The vestibular system is our sixth sense and is important for spatial perception functions, yet the sensory detection and discrimination properties of vestibular neurons remain relatively unexplored. Here we have used signal detection theory to measure detection thresholds of otolith afferents using 1 Hz linear accelerations delivered along three cardinal axes. Direction detection thresholds were measured by comparing mean firing rates centered on response peak and trough (full-cycle thresholds) or by comparing peak/trough firing rates with spontaneous activity (half-cycle thresholds). Thresholds were similar for utricular and saccular afferents, as well as for lateral, fore/aft, and vertical motion directions. When computed along the preferred direction, full-cycle direction detection thresholds were 7.54 and 3.01 cm/s(2) for regular and irregular firing otolith afferents, respectively. Half-cycle thresholds were approximately double, with excitatory thresholds being half as large as inhibitory thresholds. The variability in threshold among afferents was directly related to neuronal gain and did not depend on spike count variance. The exact threshold values depended on both the time window used for spike count analysis and the filtering method used to calculate mean firing rate, although differences between regular and irregular afferent thresholds were independent of analysis parameters. The fact that minimum thresholds measured in macaque otolith afferents are of the same order of magnitude as human behavioral thresholds suggests that the vestibular periphery might determine the limit on our ability to detect or discriminate small differences in head movement, with little noise added during downstream processing

Population-scale organization of cerebellar granule neuron signaling during a visuomotor behavior.

Granule cells at the input layer of the cerebellum comprise over half the neurons in the human brain and are thought to be critical for learning. However, little is known about granule neuron signaling at the population scale during behavior. We used calcium imaging in awake zebrafish during optokinetic behavior to record transgenically identified granule neurons throughout a cerebellar population. A significant fraction of the population was responsive at any given time. In contrast to core precerebellar populations, granule neuron responses were relatively heterogeneous, with variation in the degree of rectification and the balance of positive versus negative changes in activity. Functional correlations were strongest for nearby cells, with weak spatial gradients in the degree of rectification and the average sign of response. These data open a new window upon cerebellar function and suggest granule layer signals represent elementary building blocks under-represented in core sensorimotor pathways, thereby enabling the construction of novel patterns of activity for learning

Vestibular heading discrimination and sensitivity to linear acceleration in head and world coordinates

Effective navigation and locomotion depend critically on an observer\u27s ability to judge direction of linear self-motion, i.e., heading. The vestibular cue to heading is the direction of inertial acceleration that accompanies transient linear movements. This cue is transduced by the otolith organs. The otoliths also respond to gravitational acceleration, so vestibular heading discrimination could depend on (1) the direction of movement in head coordinates (i.e., relative to the otoliths), (2) the direction of movement in world coordinates (i.e., relative to gravity), or (3) body orientation (i.e., the direction of gravity relative to the otoliths). To quantify these effects, we measured vestibular and visual discrimination of heading along azimuth and elevation dimensions with observers oriented both upright and side-down relative to gravity. We compared vestibular heading thresholds with corresponding measurements of sensitivity to linear motion along lateral and vertical axes of the head (coarse direction discrimination and amplitude discrimination). Neither heading nor coarse direction thresholds depended on movement direction in world coordinates, demonstrating that the nervous system compensates for gravity. Instead, they depended similarly on movement direction in head coordinates (better performance in the horizontal plane) and on body orientation (better performance in the upright orientation). Heading thresholds were correlated with, but significantly larger than, predictions based on sensitivity in the coarse discrimination task. Simulations of a neuron/anti-neuron pair with idealized cosine-tuning properties show that heading thresholds larger than those predicted from coarse direction discrimination could be accounted for by an amplitude-response nonlinearity in the neural representation of inertial motion

Prepontine non-giant neurons drive flexible escape behavior in zebrafish

Many species execute ballistic escape reactions to avoid imminent danger. Despite fast reaction times, responses are often highly regulated, reflecting a trade-off between costly motor actions and perceived threat level. However, how sensory cues are integrated within premotor escape circuits remains poorly understood. Here, we show that in zebrafish, less precipitous threats elicit a delayed escape, characterized by flexible trajectories, which are driven by a cluster of 38 prepontine neurons that are completely separate from the fast escape pathway. Whereas neurons that initiate rapid escapes receive direct auditory input and drive motor neurons, input and output pathways for delayed escapes are indirect, facilitating integration of cross-modal sensory information. These results show that rapid decision-making in the escape system is enabled by parallel pathways for ballistic responses and flexible delayed actions and defines a neuronal substrate for hierarchical choice in the vertebrate nervous system

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 145

This bibliography lists 301 reports, articles, and other documents introduced into the NASA scientific and technical information system in August 1975

Alpha9 nicotinic acetylcholine receptors and the treatment of pain

Chronic pain is a vexing worldwide problem that causes substantial disability and consumes significant medical resources. Although there are numerous analgesic medications, these work through a small set of molecular mechanisms. Even when these medications are used in combination, substantial amounts of pain often remain. It is therefore highly desirable to develop treatments that work through distinct mechanisms of action. While agonists of nicotinic acetylcholine receptors (nAChRs) have been intensively studied, new data suggest a role for selective antagonists of nAChRs. α-Conotoxins are small peptides used offensively by carnivorous marine snails known as Conus. A subset of these peptides known as α-conotoxins RgIA and Vc1.1 produces both acute and long lasting analgesia. In addition, these peptides appear to accelerate the recovery of function after nerve injury, possibly through immune mediated mechanisms. Pharmacological analysis indicates that RgIA and Vc1.1 are selective antagonists of α9α10 nAChRs. A recent study also reported that these α9α10 antagonists are also potent GABA-B agonists. In the current study, we were unable to detect RgIA or Vc1.1 binding to or action on cloned GABA-B receptors expressed in HEK cells or Xenopus oocytes. We review the background, findings and implications of use of compounds that act on α9* nAChRs.11* indicates the possible presence of additional subunits.Fil: McIntosh, J. Michael. University of Utah; Estados UnidosFil: Absalom, Nathan. The University of Sydney; AustraliaFil: Chebib, Mary. The University of Sydney; AustraliaFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; ArgentinaFil: Vincler, Michelle. Wake Forest University Health Sciences; Estados Unido

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 165, March 1977

This bibliography lists 198 reports, articles, and other documents introduced into the NASA scientific and technical information system in February 1977

Aerospace Medicine and Biology. A continuing bibliography with indexes

This bibliography lists 244 reports, articles, and other documents introduced into the NASA scientific and technical information system in February 1981. Aerospace medicine and aerobiology topics are included. Listings for physiological factors, astronaut performance, control theory, artificial intelligence, and cybernetics are included

Integrated Research Plan to Assess the Combined Effects of Space Radiation, Altered Gravity, and Isolation and Confinement on Crew Health and Performance: Problem Statement

Future crewed exploration missions to Mars could last up to three years and will expose astronauts to unprecedented environmental challenges. Challenges to the nervous system during these missions will include factors of: space radiation that can damage sensitive neurons in the central nervous system (CNS); isolation and confinement can affect cognition and behavior; and altered gravity that will change the astronauts perception of their environment and their spatial orientation, and will affect their coordination, balance, and locomotion. In the past, effects of spaceflight stressors have been characterized individually. However, long-term, simultaneous exposure to multiple stressors will produce a range of interrelated behavioral and biological effects that have the potential to adversely affect operationally relevant crew performance. These complex environmental challenges might interact synergistically and increase the overall risk to the health and performance of the astronaut. Therefore, NASAs Human Research Program (HRP) has directed an integrated approach to characterize and mitigate the risk to the CNS from simultaneous exposure to these multiple spaceflight factors. The proposed research strategy focuses on systematically evaluating the relationships among three existing research risks associated with spaceflight: Risk of Acute (In-flight) and Late Central Nervous System Effects from Radiation (CNS), Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders (BMed), and Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Spaceflight (SM). NASAs HRP approach is intended to identify the magnitude and types of interactions as they affect behavior, especially as it relates to operationally relevant performance (e.g., performance that depends on reaction time, procedural memory, etc.). In order to appropriately characterize this risk of multiple spaceflight environmental stressors, there is a recognition of the need to leverage research approaches using appropriate animal models and behavioral constructs. Very little has been documented on the combined effects of altered gravity, space radiation, and other psychological and cognitive stressors on the CNS. Preliminary evidence from rodents suggest that a combination of a minimum of exposures to even two of three stressors of: simulated space radiation, simulated microgravity, and simulated isolation and confinement, have produced different and more pronounced biological and performance effects than exposure to these same stressors individually. Structural and functional changes to the CNS of rodents exposed to transdisciplinary combined stressors indicate that important processes related to information processing are likely altered including impairment of exploratory and risk taking behaviors, as well as executive function including learning, memory, and cognitive flexibility all of which may be linked to changes in related operational relevant performance. The fully integrated research plan outlines approaches to evaluate how combined, potentially synergistic, impacts of simultaneous exposures to spaceflight hazards will affect an astronauts CNS and their operationally relevant performance during future exploration missions, including missions to the Moon and Mars. The ultimate goals are to derive risk estimates for the combined, potentially synergistic, effects of the three major spaceflight hazards that will establish acceptable maximum decrement or change in a physiological or behavioral parameters during or after spaceflight, the acceptable limit of exposure to a spaceflight factor, and to evaluate strategies to mitigate any associated decrements in operationally relevant performance