Boring's formulation: a scheme for identifying functional neuron groups in a sensory system

In 1935 Edwin Boring proposed that each attribute of sensation reflects the activity of a different neural circuit. If this idea is valid, it could facilitate both psychophysical and neurophysiological research on sensory systems. We think it likely that Boring's formulation is correct for three reasons: 1) Different sensory attributes reflect conscious information about different parameters of a stimulus. To be measured by any device, each of these parameters must be individually computed. Different neural circuits would appear to be necessary for the nervous system to carry out these different computations. 2) Perceived information about different sensory attributes can be made to diverge by appropriate manipulations of the stimuli. If there is a rigorous relationship between conscious sensory experience and neural activity, such a divergence implies that different sensory attributes are served by different neural circuits. 3) Accurate information about a sensory attribute requires that a human observer's attention be focused on that attribute. Changes in direction of attention are thought to involve a process of switching from one neural circuit to another, and provide another way to cause perceived information about different sensory attributes to diverge.     

Musings on the wanderer: what's new in our understanding of vago-vagal reflexes? III. Activity-dependent plasticity in vago-vagal reflexes controlling the stomach

Vago-vagal reflex circuits modulate digestive functions from the oral cavity to the transverse colon. Previous articles in this series have described events at the level of the sensory receptors encoding the peripheral stimuli, the transmission of information in the afferent vagus, and the conversion of this data within the dorsal vagal complex (DVC) to impulses in the preganglionic efferents. The control by vagal efferents of the postganglionic neurons impinging on the glands and smooth muscles of the target organs has also been illustrated. Here we focus on some of the mechanisms by which these apparently static reflex circuits can be made quite plastic as a consequence of the action of modulatory inputs from other central nervous system sources. A large body of evidence has shown that the neuronal elements that constitute these brain stem circuits have nonuniform properties and function differently according to status of their target organs and the level of activity in critical modulatory inputs. We propose that DVC circuits undergo a certain amount of short-term plasticity that allows the brain stem neuronal elements to act in harmony with neural systems that control behavioral and physiological homeostasis.     

Real-time multimodal optical control of neurons and muscles in freely behaving Caenorhabditis elegans

The ability to optically excite or silence specific cells using optogenetics has become a powerful tool to interrogate the nervous system. Optogenetic experiments in small organisms have mostly been performed using whole-field illumination and genetic targeting, but these strategies do not always provide adequate cellular specificity. Targeted illumination can be a valuable alternative but it has only been shown in motionless animals without the ability to observe behavior output. We present a real-time, multimodal illumination technology that allows both tracking and recording the behavior of freely moving C. elegans while stimulating specific cells that express channelrhodopsin-2 or MAC. We used this system to optically manipulate nodes in the C. elegans touch circuit and study the roles of sensory and command neurons and the ultimate behavioral output. This technology enhances our ability to control, alter, observe and investigate how neurons, muscles and circuits ultimately produce behavior in animals using optogenetics.     

Cortical maps: a role for astrocytes?

Astrocytes are a multifunctional cell type in the nervous system that can influence neurons and synapses in numerous ways. Astrocytes have been suggested to play important roles in synapse formation during development, as well as in multiple forms of synaptic plasticity in the developing and adult brain. Astrocytes respond to nearby neural activity with elevations in cytosolic calcium concentration, and in sensory cortex these calcium responses have been shown to be topographically aligned to neuronal sensory maps. Here, we review recent evidence for astrocyte interactions with neural circuits, with particular emphasis on how these interactions may shape the development, arrangement and plasticity of cortical sensory maps.     

Neuromechanics of muscle synergies for posture and movement

Recent research suggests that the nervous system controls muscles by activating flexible combinations of muscle synergies to produce a wide repertoire of movements. Muscle synergies are like building blocks, defining characteristic patterns of activation across multiple muscles that may be unique to each individual, but perform similar functions. The identification of muscle synergies has strong implications for the organization and structure of the nervous system, providing a mechanism by which task-level motor intentions are translated into detailed, low-level muscle activation patterns. Understanding the complex interplay between neural circuits and biomechanics that give rise to muscle synergies will be crucial to advancing our understanding of neural control mechanisms for movement.     

Plasticity of central autonomic neural circuits in diabetes

Regulation of energy metabolism is controlled by the brain, in which key central neuronal circuits process a variety of information reflecting nutritional state. Special sensory and gastrointestinal afferent neural signals, along with blood-borne metabolic signals, impinge on parallel central autonomic circuits located in the brainstem and hypothalamus to signal changes in metabolic balance. Specifically, neural and humoral signals converge on the brainstem vagal system and similar signals concentrate in the hypothalamus, with significant overlap between both sensory and motor components of each system and extensive cross-talk between the systems. This ultimately results in production of coordinated regulatory autonomic and neuroendocrine cues to maintain energy homeostasis. Therapeutic metabolic adjustments can be accomplished by modulating viscerosensory input or autonomic motor output, including altering parasympathetic circuitry related to GI, pancreas, and liver regulation. These alterations can include pharmacological manipulation, but surgical modification of neural signaling should also be considered. In addition, central control of visceral function is often compromised by diabetes mellitus, indicating that circuit modification should be studied in the context of its effect on neurons in the diabetic state. Diabetes has traditionally been handled as a peripheral metabolic disease, but the central nervous system plays a crucial role in regulating glucose homeostasis. This review focuses on key autonomic brain areas associated with management of energy homeostasis and functional changes in these areas associated with the development of diabetes.     

The remapping of space in motor learning and human–machine interfaces

Studies of motor adaptation to patterns of deterministic forces have revealed the ability of the motor control system to form and use predictive representations of the environment. One of the most fundamental elements of our environment is space itself. This article focuses on the notion of Euclidean space as it applies to common sensory motor experiences. Starting from the assumption that we interact with the world through a system of neural signals, we observe that these signals are not inherently endowed with metric properties of the ordinary Euclidean space. The ability of the nervous system to represent these properties depends on adaptive mechanisms that reconstruct the Euclidean metric from signals that are not Euclidean. Gaining access to these mechanisms will reveal the process by which the nervous system handles novel sophisticated coordinate transformation tasks, thus highlighting possible avenues to create functional human–machine interfaces that can make that task much easier. A set of experiments is presented that demonstrate the ability of the sensory-motor system to reorganize coordination in novel geometrical environments. In these environments multiple degrees of freedom of body motions are used to control the coordinates of a point in a two-dimensional Euclidean space. We discuss how practice leads to the acquisition of the metric properties of the controlled space. Methods of machine learning based on the reduction of reaching errors are tested as a means to facilitate learning by adaptively changing he map from body motions to controlled device. We discuss the relevance of the results to the development of adaptive human–machine interfaces and optimal control.     

Rhythmic behaviour and pattern-generating circuits in the locust: Key concepts and recent updates

There is growing recognition that rhythmic activity patterns are widespread in our brain and play an important role in all aspects of the functioning of our nervous system, from sensory integration to central processing and motor control. The study of the unique properties that enable central circuits to generate their rhythmic output in the absence of any patterned, sensory or descending, inputs, has been very rewarding in the relatively simple invertebrate preparations. The locust, specifically, is a remarkable example of an organism in which central pattern generator (CPG) networks have been suggested and studied in practically all aspects of their behaviour. Here we present an updated overview of the various rhythmic behaviours in the locust and aspects of their neural control. We focus on the fundamental concepts of multifunctional neuronal circuits, neural centre interactions and neuromodulation of CPG networks. We are certain that the very broad and solid knowledge base of locust rhythmic behaviour and pattern-generating circuits will continue to expand and further contribute to our understanding of the principles behind the functioning of the nervous system and, indeed, the brain.     

Functions of microglia in the central nervous system--beyond the immune response

Microglia cells are the immune cells of the central nervous system and consequently play important roles in brain infections and inflammation. Recent in vivo imaging studies have revealed that in the resting healthy brain, microglia are highly dynamic, moving constantly to actively survey the brain parenchyma. These active microglia can rapidly respond to pathological insults, becoming activated to induce a range of effects that may contribute to both pathogenesis, or to confer neuronal protection. However, interactions between microglia and neurons are being recognized as important in shaping neural circuit activity under more normal, physiological conditions. During development and neurogenesis, microglia interactions with neurons help to shape the final patterns of neural circuits important for behavior and with implications for diseases. In the mature brain, microglia can respond to changes in sensory activity and can influence neuronal activity acutely and over the long term. Microglia seem to be particularly involved in monitoring the integrity of synaptic function. In this review, we discuss some of these new insights into the involvement of microglia in neural circuits.     

Smelling on the fly: sensory cues and strategies for olfactory navigation in Drosophila

Navigating toward (or away from) a remote odor source is a challenging problem that requires integrating olfactory information with visual and mechanosensory cues. Drosophila melanogaster is a useful organism for studying the neural mechanisms of these navigation behaviors. There are a wealth of genetic tools in this organism, as well as a history of inventive behavioral experiments. There is also a large and growing literature in Drosophila on the neural coding of olfactory, visual, and mechanosensory stimuli. Here we review recent progress in understanding how these stimulus modalities are encoded in the Drosophila nervous system. We also discuss what strategies a fly might use to navigate in a natural olfactory landscape while making use of all these sources of sensory information. We emphasize that Drosophila are likely to switch between multiple strategies for olfactory navigation, depending on the availability of various sensory cues. Finally, we highlight future research directions that will be important in understanding the neural circuits that underlie these behaviors.     

Corollary discharge across the animal kingdom

Our movements can hinder our ability to sense the world. Movements can induce sensory input (for example, when you hit something) that is indistinguishable from the input that is caused by external agents (for example, when something hits you). It is critical for nervous systems to be able to differentiate between these two scenarios. A ubiquitous strategy is to route copies of movement commands to sensory structures. These signals, which are referred to as corollary discharge (CD), influence sensory processing in myriad ways. Here we review the CD circuits that have been uncovered by neurophysiological studies and suggest a functional taxonomic classification of CD across the animal kingdom. This broad understanding of CD circuits lays the groundwork for more challenging studies that combine neurophysiology and psychophysics to probe the role of CD in perception.     

The neural circuits and synaptic mechanisms underlying motor initiation in C. elegans

C. elegans is widely used to dissect how neural circuits and genes generate behavior. During locomotion, worms initiate backward movement to change locomotion direction spontaneously or in response to sensory cues; however, the underlying neural circuits are not well defined. We applied a multidisciplinary approach to map neural circuits in freely behaving worms by integrating functional imaging, optogenetic interrogation, genetic manipulation, laser ablation, and electrophysiology. We found that a disinhibitory circuit and a stimulatory circuit together promote initiation of backward movement and that circuitry dynamics is differentially regulated by sensory cues. Both circuits require glutamatergic transmission but depend on distinct glutamate receptors. This dual mode of motor initiation control is found in mammals, suggesting that distantly related organisms with anatomically distinct nervous systems may adopt similar strategies for motor control. Additionally, our studies illustrate how a multidisciplinary approach facilitates dissection of circuit and synaptic mechanisms underlying behavior in a genetic model organism.     

Structure and metamorphic remodeling of the larval nervous system and musculature of Phoronis pallida (Phoronida)

The structure of the larval nervous system and the musculature of Phoronis pallida were studied, as well as the remodeling of these systems at metamorphosis. The serotonergic portion of the apical ganglion is a U-shaped field of cell bodies that send projections into a central neuropil. The majority of the serotonergic cells are (at least) bipolar sensory cells, and a few are nonsensory cells. Catecholaminergic cell bodies border the apical ganglion. The second (hood) sense organ develops at competence and is composed of bipolar sensory cells that send projections into a secondary neuropil. Musculature of the competent larva includes circular and longitudinal muscle fibers of the body wall, as well as elevators and depressors of the tentacles and hood. The juvenile nervous system and musculature are developed prior to metamorphosis and are integrated with those of the larva. Components of the juvenile nervous system include a diffuse neural net of serotonergic cell bodies and fibers and longitudinal catecholaminergic fibers. The juvenile body wall musculature consists of longitudinal fibers that overlie circular muscle fibers, except in the cincture regions, where this pattern is reversed. Metamorphosis is initiated by the larval neuromuscular system but is completed by the juvenile neuromuscular system. During metamorphosis, the larval nervous system and the musculature undergo cell death, and the larval tentacles and gut are remodeled into the juvenile arrangement. Although the phoronid nervous system has often been described as deuterostome-like, these data show that several cytological aspects of the larval and juvenile neuromuscular systems also have protostome (lophotrochozoan) characteristics.     

Control and modulation of canal driven vestibulo-ocular reflex.

It has been well known that the canal driven vestibulo-ocular reflex (VOR) is controlled and modulated through the central nervous system by external sensory information (e.g. visual, otolithic and somatosensory inputs) and by mental conditions. Because the origin of retinal image motion exists both in the subjects (eye, head and body motions) and in the external world (object motion), the head motion should be canceled and/or the object should be followed by smooth eye movements. Human has developed a lot of central nervous mechanisms for smooth eye movements (e.g. VOR, optokinetic reflex and smooth pursuit eye movements). These mechanisms are thought to work for the purpose of better seeing. Distinct mechanism will work in appropriate self motion and/or object motion. As the results, whole mechanisms are controlled in a purpose-directed manner. This can be achieved by a self-organizing holistic system. Holistic system is very useful for understanding human oculomotor behavior.     

Studies of stimulus-evoked responses in single motoneurones in humans.

Surface electromyography (EMG) has been a powerful technique for studying reflex and other stimulus-evoked responses in the human nervous system. However, important additional insights can be gained into the operation of neural circuits by studying the responses of single motor units to various stimuli. In this paper, some of the advantages of single motor unit recording will be canvassed, and some examples of the application to this method to the study of reflex responses to sensory stimuli and brain stimulation will be presented.     

Abnormalities in the awareness and control of action

Much of the functioning of the motor system occurs without awareness. Nevertheless, we are aware of some aspects of the current state of the system and we can prepare and make movements in the imagination. These mental representations of the actual and possible states of the system are based on two sources: sensory signals from skin and muscles, and the stream of motor commands that have been issued to the system. Damage to the neural substrates of the motor system can lead to abnormalities in the awareness of action as well as defects in the control of action. We provide a framework for understanding how these various abnormalities of awareness can arise. Patients with phantom limbs or with anosognosia experience the illusion that they can move their limbs. We suggest that these representations of movement are based on streams of motor commands rather than sensory signals. Patients with utilization behaviour or with delusions of control can no longer properly link their intentions to their actions. In these cases the impairment lies in the representation of intended movements. The location of the neural damage associated with these disorders suggests that representations of the current and predicted state of the motor system are in parietal cortex, while representations of intended actions are found in prefrontal and premotor cortex.     

The Sense Organs and Ventral Ganglion of Sagitta (Chaetognatha)

This paper describes some features of the chaetognath nervous system from ultrastructural observations and observations on material stained with specific techniques for nervous tissue, and from records of the activity of the locomotor muscles and ventral ganglion. Sensory cells grouped on the ventral surface of the head bear ciliary processes (some with multiple tubules), and are probably in connexion with the central nervous system by their own axons, unlike the sensory cells of the hair fan vibration receptors of head and body. The ventral ganglion is motor to the locomotor muscles of the body, and controls the rhythmic locomotor activity of the animal. Electrical events associated with contraction of these muscles are compound non-overshooting spike-like potentials. The ventral ganglion contains several large nerve fibres constant in position and connexions in different individuals. Some of these arise from cells in the ganglia of the head, and pass to the ventral ganglion, others from cells within the ventral ganglion, and probably supply the ciliary hair fan receptors of the body, whilst the motor axons issuing from the ventral ganglion are smaller in diameter. The ganglion is arranged on a ladder-like plan, and axons of the lateral cell bodies cross the central neuropil transversely before they contribute to the longitudinal tracts or pass out in the radial nerves. Synapses in the neuropil contain 30–40 nm electron lucent vesicles; the transmitter is unknown, but is unlikely to be either acetylcholine or l -glutamate. Occasional larger electron dense vesicles up to 70 nm in diameter are also found within nerve fibres of the neuropil. It is concluded that the arrangement of the peripheral nervous system is unlike that of several groups which have been suggested as related to chaetognaths.     

Contributions of electric fish to the understanding of sensory processing by reafferent systems.

Sensory systems must solve the inverse problem of determining environmental events based on patterns of neural activity in the central nervous system that are affected by those environmental events. Different environmental events can give rise to indistinguishable patterns of neural activity, so that there will often, perhaps even always, be multiple solutions to a sensory inverse problem. Imaging strategies and brain organization confine these multiple solutions within a bounded set. Three different active strategies may be employed by animals to constrain the number of solutions to the sensory inverse problem: active generation of the energy (carrier) that stimulates receptors; reorientation of the point of view; and control of signal conditioning before transduction (pre-receptor mechanisms). This paper describes how these strategies are used in sensory-motor systems, using electric fish as a paradigmatic example. Carrier generation and receptor tuning to the carrier improve signal to noise ratio. Receptor tuning to different frequency bands of the carrier spectrum allows a sensory system to evaluate different kinds of carrier modulations and to extract the different features of objects in the environment. Pre-receptor mechanisms condition the signals, optimizing their detection at a foveal region where the sensory resolution is maximum. Active orientation of the sensory surface redirects the fovea to explore in detail the source of interesting signals. Sensory input generated by these active exploration mechanisms ('reafference') has two components: one, necessary, derived from the self-generated actions and another, contingent, consisting of the information obtained from the external world. Extracting environmental information ('exafference') requires that the self generated afference be subtracted from the sensory inflow. Such subtraction is often associated with the generation and storage of expectations about sensory inputs. It can be concluded that an animal's perceptual world and its ability to transform the world are inextricably linked. Understanding sensory systems must, therefore, always require understanding the organization of motor behavior.