Activation of Parallel Fiber Feedback by Spatially Diffuse Stimuli Reduces Signal and Noise Correlations via Independent Mechanisms in a Cerebellum-Like Structure

Correlations between the activities of neighboring neurons are observed ubiquitously across systems and species and are dynamically regulated by several factors such as the stimulus'' spatiotemporal extent as well as by the brain''s internal state. Using the electrosensory system of gymnotiform weakly electric fish, we recorded the activities of pyramidal cell pairs within the electrosensory lateral line lobe (ELL) under spatially localized and diffuse stimulation. We found that both signal and noise correlations were markedly reduced (>40%) under the latter stimulation. Through a network model incorporating key anatomical features of the ELL, we reveal how activation of diffuse parallel fiber feedback from granule cells by spatially diffuse stimulation can explain both the reduction in signal as well as the reduction in noise correlations seen experimentally through independent mechanisms. First, we show that burst-timing dependent plasticity, which leads to a negative image of the stimulus and thereby reduces single neuron responses, decreases signal but not noise correlations. Second, we show trial-to-trial variability in the responses of single granule cells to sensory input reduces noise but not signal correlations. Thus, our model predicts that the same feedback pathway can simultaneously reduce both signal and noise correlations through independent mechanisms. To test this prediction experimentally, we pharmacologically inactivated parallel fiber feedback onto ELL pyramidal cells. In agreement with modeling predictions, we found that inactivation increased both signal and noise correlations but that there was no significant relationship between magnitude of the increase in signal correlations and the magnitude of the increase in noise correlations. The mechanisms reported in this study are expected to be generally applicable to the cerebellum as well as other cerebellum-like structures. We further discuss the implications of such decorrelation on the neural coding strategies used by the electrosensory and by other systems to process natural stimuli.     

Information-processing demands in electrosensory and mechanosensory lateral line systems.

The electrosensory and mechanosensory lateral line systems of fish exhibit many common features in their structural and functional organization, both at the sensory periphery as well as in central processing pathways. These two sensory systems also appear to play similar roles in many behavioral tasks such as prey capture, orientation with respect to external environmental cues, navigation in low-light conditions, and mediation of interactions with nearby animals. In this paper, we briefly review key morphological, physiological, and behavioral aspects of these two closely related sensory systems. We present arguments that the information processing demands associated with spatial processing are likely to be quite similar, due largely to the spatial organization of both systems and the predominantly dipolar nature of many electrosensory and mechanosensory stimulus fields. Demands associated with temporal processing may be quite different, however, due primarily to differences in the physical bases of electrosensory and mechanosensory stimuli (e.g. speed of transmission). With a better sense of the information processing requirements, we turn our attention to an analysis of the functional organization of the associated first-order sensory nuclei in the hindbrain, including the medial octavolateral nucleus (MON), dorsal octavolateral nucleus (DON), and electrosensory lateral line lobe (ELL). One common feature of these systems is a set of neural mechanisms for improving signal-to-noise ratios, including mechanisms for adaptive suppression of reafferent signals. This comparative analysis provides new insights into how the nervous system extracts biologically significant information from dipolar stimulus fields in order to solve a variety of behaviorally relevant problems faced by aquatic animals.     

Distribution of Kv1-like potassium channels in the electromotor and electrosensory systems of the weakly electric fish Apteronotus leptorhynchus

The electromotor and electrosensory systems of the weakly electric fish Apteronotus leptorhynchus are model systems for studying mechanisms of high-frequency motor pattern generation and sensory processing. Voltage-dependent ionic currents, including low-threshold potassium currents, influence excitability of neurons in these circuits and thereby regulate motor output and sensory filtering. Although Kv1-like potassium channels are likely to carry low-threshold potassium currents in electromotor and electrosensory neurons, the distribution of Kv1 alpha subunits in A. leptorhynchus is unknown. In this study, we used immunohistochemistry with six different antibodies raised against specific mammalian Kv1 alpha subunits (Kv1.1-Kv1.6) to characterize the distribution of Kv1-like channels in electromotor and electrosensory structures. Each Kv1 antibody labeled a distinct subset of neurons, fibers, and/or dendrites in electromotor and electrosensory nuclei. Kv1-like immunoreactivity in the electrosensory lateral line lobe (ELL) and pacemaker nucleus are particularly relevant in light of previous studies suggesting that potassium currents carried by Kv1 channels regulate neuronal excitability in these regions. Immunoreactivity of pyramidal cells in the ELL with several Kv1 antibodies is consistent with Kv1 channels carrying low-threshold outward currents that regulate spike waveform in these cells (Fernandez et al., J Neurosci 2005;25:363-371). Similarly, Kv1-like immunoreactivity in the pacemaker nucleus is consistent with a role of Kv1 channels in spontaneous high-frequency firing in pacemaker neurons. Robust Kv1-like immunoreactivity in several other structures, including the dorsal torus semicircularis, tuberous electroreceptors, and the electric organ, indicates that Kv1 channels are broadly expressed and are likely to contribute significantly to generating the electric organ discharge and processing electrosensory inputs.     

Developmental origin of shark electrosensory organs

Vertebrates have evolved electrosensory receptors that detect electrical stimuli on the surface of the skin and transmit them somatotopically to the brain. In chondrichthyans, the electrosensory system is composed of a cephalic network of ampullary organs, known as the ampullae of Lorenzini, that can detect extremely weak electric fields during hunting and navigation. Each ampullary organ consists of a gel-filled epidermal pit containing sensory hair cells, and synaptic connections with primary afferent neurons at the base of the pit that facilitate detection of voltage gradients over large regions of the body. The developmental origin of electroreceptors and the mechanisms that determine their spatial arrangement in the vertebrate head are not well understood. We have analyzed electroreceptor development in the lesser spotted catshark (Scyliorhinus canicula) and show that Sox8 and HNK1, two markers of the neural crest lineage, selectively mark sensory cells in ampullary organs. This represents the first evidence that the neural crest gives rise to electrosensory cells. We also show that pathfinding by cephalic mechanosensory and electrosensory axons follows the expression pattern of EphA4, a well-known guidance cue for axons and neural crest cells in osteichthyans. Expression of EphrinB2, which encodes a ligand for EphA4, marks the positions at which ampullary placodes are initiated in the epidermis, and EphA4 is expressed in surrounding mesenchyme. These results suggest that Eph-Ephrin signaling may establish an early molecular map for neural crest migration, axon guidance and placodal morphogenesis during development of the shark electrosensory system.     

Design principles of sensory processing in cerebellum-like structures

Cerebellum-like structures are compared for two sensory systems: electrosensory and auditory. The electrosensory lateral line lobe of mormyrid electric fish is reviewed and the neural representation of electrosensory objects in this structure is modeled and discussed. The dorsal cochlear nucleus in the auditory brainstem of mammals is reviewed and new data are presented that characterize the responses of neurons in this structure in the mouse. Similarities between the electrosensory and auditory cerebellum-like structures are shown, in particular adaptive processes that may reduce responses to predictable stimuli. We suggest that the differences in the types of sensory objects may drive the differences in the anatomical and physiological characteristics of these two cerebellum-like structures.     

SK channel subtypes enable parallel optimized coding of behaviorally relevant stimulus attributes: A review

Ion channels play essential roles toward determining how neurons respond to sensory input to mediate perception and behavior. Small conductance calcium-activated potassium (SK) channels are found ubiquitously throughout the brain and have been extensively characterized both molecularly and physiologically in terms of structure and function. It is clear that SK channels are key determinants of neural excitability as they mediate important neuronal response properties such as spike frequency adaptation. However, the functional roles of the different known SK channel subtypes are not well understood. Here we review recent evidence from the electrosensory system of weakly electric fish suggesting that the function of different SK channel subtypes is to optimize the processing of independent but behaviorally relevant stimulus attributes. Indeed, natural sensory stimuli frequently consist of a fast time-varying waveform (i.e., the carrier) whose amplitude (i.e., the envelope) varies slowly and independently. We first review evidence showing how somatic SK2 channels mediate tuning and responses to carrier waveforms. We then review evidence showing how dendritic SK1 channels instead determine tuning and optimize responses to envelope waveforms based on their statistics as found in the organism's natural environment in an independent fashion. The high degree of functional homology between SK channels in electric fish and their mammalian orthologs, as well as the many important parallels between the electrosensory system and the mammalian visual, auditory, and vestibular systems, suggest that these functional roles are conserved across systems and species.     

Spatiotemporal burst coding for extracting features of spatiotemporally varying stimuli

Encoding features of spatiotemporally varying stimuli is quite important for understanding the neural mechanisms of various sensory coding. Temporal coding can encode features of time-varying stimulus, and population coding with temporal coding is adequate for encoding spatiotemporal correlation of stimulus features into spatiotemporal activity of neurons. However, little is known about how spatiotemporal features of stimulus are encoded by spatiotemporal property of neural activity. To address this issue, we propose here a population coding with burst spikes, called here spatiotemporal burst (STB) coding. In STB coding, the temporal variation of stimuli is encoded by the precise onset timing of burst spike, and the spatiotemporal correlation of stimuli is emphasized by one specific aspect of burst firing, or spike packet followed by silent interval. To show concretely the role of STB coding, we study the electrosensory system of a weakly electric fish. Weakly electric fish must perceive the information about an object nearby by analyzing spatiotemporal modulations of electric field around it. On the basis of well-characterized circuitry, we constructed a neural network model of the electrosensory system. Here we show that STB coding encodes well the information of object distance and size by extracting the spatiotemporal correlation of the distorted electric field. The burst activity of electrosensory neurons is also affected by feedback signals through synaptic plasticity. We show that the control of burst activity caused by the synaptic plasticity leads to extracting the stimulus features depending on the stimulus context. Our results suggest that sensory systems use burst spikes as a unit of sensory coding in order to extract spatiotemporal features of stimuli from spatially distributed stimuli.     

Adaptive processing in electrosensory systems: Links to cerebellar plasticity and learning

The first central stage of electrosensory processing in fish takes place in structures with local circuitry that resembles the cerebellum. Cerebellum-like structures and the cerebellum itself share common patterns of gene expression and may also share developmental and evolutionary origins. Given these similarities it is natural to ask whether insights gleaned from the study of cerebellum-like structures might be useful for understanding aspects of cerebellar function and vice versa. Work from electrosensory systems has shown that cerebellum-like circuitry acts to generate learned predictions about the sensory consequences of the animals’ own behavior through a process of associative plasticity at parallel fiber synapses. Subtraction of these predictions from the actual sensory input serves to highlight unexpected and hence behaviorally relevant features. Learning and prediction are also central to many current ideas regarding the function of the cerebellum itself. The present review draws comparisons between cerebellum-like structures and the cerebellum focusing on the properties and sites of synaptic plasticity in these structures and on connections between plasticity and learning. Examples are drawn mainly from the electrosensory lobe (ELL) of mormyrid fish and from extensive work characterizing the role of the cerebellum in Pavlovian eyelid conditioning and vestibulo-ocular reflex (VOR) modification. Parallels with other cerebellum-like structures, including the gymnotid ELL, the elasmobranch dorsal octavolateral nucleus (DON), and the mammalian dorsal cochlear nucleus (DCN) are also discussed.     

Encoding and processing biologically relevant temporal information in electrosensory systems

Wave-type weakly electric fish are specialists in time-domain processing: behaviors in these animals are often tightly correlated with the temporal structure of electrosensory signals. Behavioral responses in these fish can be dependent on differences in the temporal structure of electrosensory signals alone. This feature has facilitated the study of temporal codes and processing in central nervous system circuits of these animals. The temporal encoding and mechanisms used to transform temporal codes in the brain have been identified and characterized in several species, including South American gymnotid species and in the African mormyrid genus Gymnarchus. These distantly related groups use similar strategies for neural computations of information on the order of microseconds, milliseconds, and seconds. Here, we describe a suite of mechanisms for behaviorally relevant computations of temporal information that have been elucidated in these systems. These results show the critical role that behavioral experiments continue to have in the study of the neural control of behavior and its evolution.     

Phantoms in the brain: Ambiguous representations of stimulus amplitude and timing in weakly electric fish

In wave-type weakly electric fish, two distinct types of primary afferent fibers are specialized for separately encoding modulations in the amplitude and phase (timing) of electrosensory stimuli. Time-coding afferents phase lock to periodic stimuli and respond to changes in stimulus phase with shifts in spike timing. Amplitude-coding afferents fire sporadically to periodic stimuli. Their probability of firing in a given cycle, and therefore their firing rate, is proportional to stimulus amplitude. However, the spike times of time-coding afferents are also affected by changes in amplitude; similarly, the firing rates of amplitude-coding afferents are also affected by changes in phase. Because identical changes in the activity of an individual primary afferent can be caused by modulations in either the amplitude or phase of stimuli, there is ambiguity regarding the information content of primary afferent responses that can result in ‘phantom’ modulations not present in an actual stimulus. Central electrosensory neurons in the hindbrain and midbrain respond to these phantom modulations. Phantom modulations can also elicit behavioral responses, indicating that ambiguity in the encoding of amplitude and timing information ultimately distorts electrosensory perception. A lack of independence in the encoding of multiple stimulus attributes can therefore result in perceptual illusions. Similar effects may occur in other sensory systems as well. In particular, the vertebrate auditory system is thought to be phylogenetically related to the electrosensory system and it encodes information about amplitude and timing in similar ways. It has been well established that pitch perception and loudness perception are both affected by the frequency and intensity of sounds, raising the intriguing possibility that auditory perception may also be affected by ambiguity in the encoding of sound amplitude and timing.     

From sparks to spikes: information processing in the electrosensory systems of fish

Recent work on electrosensory systems in fish has combined traditional neuroethological approaches with quantitative methods for characterizing neural coding. These studies have shed light on general issues in sensory processing, including how peripheral sensory receptors encode external stimuli and how these representations are transformed at subsequent stages of processing.     

Ionic and neuromodulatory regulation of burst discharge controls frequency tuning

Sensory neurons encode natural stimuli by changes in firing rate or by generating specific firing patterns, such as bursts. Many neural computations rely on the fact that neurons can be tuned to specific stimulus frequencies. It is thus important to understand the mechanisms underlying frequency tuning. In the electrosensory system of the weakly electric fish, Apteronotus leptorhynchus, the primary processing of behaviourally relevant sensory signals occurs in pyramidal neurons of the electrosensory lateral line lobe (ELL). These cells encode low frequency prey stimuli with bursts of spikes and high frequency communication signals with single spikes. We describe here how bursting in pyramidal neurons can be regulated by intrinsic conductances in a cell subtype specific fashion across the sensory maps found within the ELL, thereby regulating their frequency tuning. Further, the neuromodulatory regulation of such conductances within individual cells and the consequences to frequency tuning are highlighted. Such alterations in the tuning of the pyramidal neurons may allow weakly electric fish to preferentially select for certain stimuli under various behaviourally relevant circumstances.     

Sensory control of behavior in electric fish

The electrosensory system is ideally suited for the integration of behavioral and cellular approaches and, therefore, has led to the most detailed explanations of natural behaviors at the single-cell level. The electric sense shares basic principles in the coding of sensory information with more advanced sensory modalities and thus provides a convenient model system for studying neuronal mechanisms of information processing in general.     

Electrolocation and electrocommunication in pulse gymnotids: signal carriers, pre-receptor mechanisms and the electrosensory mosaic.

Constraints introduced by signal carriers, pre-receptor mechanisms and receptor transduction are fundamental for shaping the signals used by the brain to build up perceptual images. This review analyses some of these constraints in the electrosensory system of pulse Gymnotids. First, it describes the characteristics and differences of electrolocation and electrocommunication carriers. Second, it analyses the role of electrogenic and non-electrogenic tissues of the fish body in the generation and conditioning of these carriers. Two pre-receptor mechanisms are discussed: (a) the funneling of currents to the perioral region and (b) a Mexican-hat profile involved in edge detection. Finally, some characteristics of the electroreceptor structure and the sensory mosaic are examined. We conclude that there is an electrosensory fovea at the perioral region where a large density and variety of receptors is stimulated by self- and conspecific-generated currents funneled there by non electrogenic tissues. Differences in carrier waveform may be used to distinguish between reafferent and communication signals.     

Neural simulations of adaptive reafference suppression in the elasmobranch electrosensory system

The electrosensory system of elasmobranchs is extremely sensitive to weak electric fields, with behavioral thresholds having been reported at voltage gradients as low as 5 nV/cm. To achieve this amazing sensitivity, the electrosensory system must extract weak extrinsic signals from a relatively large reafferent background signal associated with the animal's own movements. Ventilatory movements, in particular, strongly modulate the firing rates of primary electrosensory afferent nerve fibers, but this modulation is greatly suppressed in the medullary electrosensory processing nucleus, the dorsal octavolateral nucleus. Experimental evidence suggests that the neural basis of reafference suppression involves a common-mode rejection mechanism supplemented by an adaptive filter that fine tunes the cancellation. We present a neural model and computer simulation results that support the hypothesis that the adaptive component may involve an anti-Hebbian form of synaptic plasticity at molecular layer synapses onto ascending efferent neurons, the principal output neurons of the nucleus. Parallel fibers in the molecular layer carry a wealth of proprioceptive, efference copy, and sensory signals related to the animal's own movements. The proposed adaptive mechanism acts by canceling out components of the electrosensory input signal that are consistently correlated with these internal reference signals.Abbreviations AEN ascending efferent neuron - AFF primary afferent nerve fiber - DGR dorsal granular ridge - DON dorsal octavolateral nucleus - ELL electrosensory lateral line lobe - GABA -aminobutyric acid - IN inhibitory interneuron - ISI interspike interval - ST stellate cell     

A comparison of the electrosensory morphology of a euryhaline and a marine stingray

The electrosensory system is found in all chondrichthyan fishes and is used for several biological functions, most notably prey detection. Variation in the physical parameters of a habitat type, i.e. water conductivity, may influence the morphology of the electrosensory system. Thus, the electrosensory systems of freshwater rays are considerably different from those of fully marine species; however, little research has so far examined the morphology and distribution of these systems in euryhaline elasmobranchs. The present study investigates and compares the morphology and distribution of electrosensory organs in two sympatric stingray species: the (euryhaline) estuary stingray, Dasyatis fluviorum, and the (marine) blue-spotted maskray, Neotrygon kuhlii. Both species possess a significantly higher number of ventral electrosensory pores than previously assessed elasmobranchs. This correlates with a diet consisting of benthic infaunal and epifaunal prey, where the electrosensory pore distribution patterns are likely to be a function of both ecology and phylogeny. The gross morphology of the electrosensory system in D. fluviorum is more similar to that of other marine elasmobranch species, rather than that of freshwater species. Both D. fluviorum and N. kuhlii possess ‘macro-ampullae’ with branching canals leading to several alveoli. The size of the pores and the length of the canals in D. fluviorum are smaller than in N. kuhlii, which is likely to be an adaptation to habitats with lower conductivity. This study indicates that the morphology of the electrosensory system in a euryhaline elasmobranch species seems very similar to that of their fully marine counterparts. However, some morphological differences are present between these two sympatric species, which are thought to be linked to their habitat type.     

Are mushroom bodies cerebellum-like structures?

The mushroom bodies are distinctive neuropils in the protocerebral brain segments of many protostomes. A defining feature of mushroom bodies is their intrinsic neurons, masses of cytoplasm-poor globuli cells that form a system of lobes with their densely-packed, parallel-projecting axon-like processes. In insects, the role of the mushroom bodies in olfactory processing and associative learning and memory has been studied in depth, but several lines of evidence suggest that the function of these higher brain centers cannot be restricted to these roles. The present account considers whether insight into an underlying function of mushroom bodies may be provided by cerebellum-like structures in vertebrates, which are similarly defined by the presence of masses of tiny granule cells that emit thin parallel fibers forming a dense molecular layer. In vertebrates, the shared neuroarchitecture of cerebellum-like structures has been suggested to underlie a common functional role as adaptive filters for the removal of predictable sensory elements, such as those arising from reafference, from the total sensory input. Cerebellum-like structures include the vertebrate cerebellum, the electrosensory lateral line lobe, dorsal and medial octavolateral nuclei of fish, and the dorsal cochlear nucleus of mammals. The many architectural and physiological features that the insect mushroom bodies share with cerebellum-like structures suggest that it might be fruitful to consider mushroom body function in light of a possible role as adaptive sensory filters. The present account thus presents a detailed comparison of the insect mushroom bodies with vertebrate cerebellum-like structures.     

Gain control in the electrosensory system: a role for the descending projections to the electrosensory lateral line lobe

The responses of E-cells, basilar pyramidal cells, of the electrosensory lateral line lobe (ELLL) were studied in normal animals (Apteronotus leptorhynchus) and in fish in which a component of the descending input from the midbrain n. praeeminentialis to the ELLL was interrupted by lesions or by application of local anesthetics. This treatment increased the responsiveness of these neurons by 100 to 300%. A method is described by which the animal's electric organ discharge (EOD) can be increased or decreased in amplitude. Responses of E-cells to a brief stationary electrosensory stimulus and to moving electrolocation targets were studied in normal and in lesioned animals with normal and altered EOD amplitudes. Large reductions in EOD amplitude, approximately 50%, result in no significant changes in the average size of E-cells' responses to either type of electrosensory stimulus in normal animals. Interruption of the descending input, however, results in a loss of the E-cells' ability to maintain constant response size when the EOD amplitude is reduced. Increases in EOD amplitude cause reductions in the size of E-cell responses to the moving electrolocation targets and to the stationary stimulus. The effects of increased EOD amplitude are present in normal animals and in animals in which the descending input is interrupted. The descending input to the ELLL seems to function as a gain control mechanism that is capable of compensating for losses in stimulus strength resulting from reduced EOD amplitude. The component of the descending input studied here does not seem to play a role in the response of the system to increases in EOD amplitude. These results are discussed in conjunction with the known details of the ELLL circuitry and its connections with other brain areas.     

Short-term depression and transient memory in sensory cortex

Persistent neuronal activity is usually studied in the context of short-term memory localized in central cortical areas. Recent studies show that early sensory areas also can have persistent representations of stimuli which emerge quickly (over tens of milliseconds) and decay slowly (over seconds). Traditional positive feedback models cannot explain sensory persistence for at least two reasons: (i) They show attractor dynamics, with transient perturbations resulting in a quasi-permanent change of system state, whereas sensory systems return to the original state after a transient. (ii) As we show, those positive feedback models which decay to baseline lose their persistence when their recurrent connections are subject to short-term depression, a common property of excitatory connections in early sensory areas. Dual time constant network behavior has also been implemented by nonlinear afferents producing a large transient input followed by much smaller steady state input. We show that such networks require unphysiologically large onset transients to produce the rise and decay observed in sensory areas. Our study explores how memory and persistence can be implemented in another model class, derivative feedback networks. We show that these networks can operate with two vastly different time courses, changing their state quickly when new information is coming in but retaining it for a long time, and that these capabilities are robust to short-term depression. Specifically, derivative feedback networks with short-term depression that acts differentially on positive and negative feedback projections are capable of dynamically changing their time constant, thus allowing fast onset and slow decay of responses without requiring unrealistically large input transients.