Reversible associative depression and nonassociative potentiation at a parallel fiber synapse

The electrosensory lobe (ELL) of mormyrid electric fish is one of several cerebellum-like sensory structures in fish that remove predictable features of the sensory inflow. This adaptive process obeys anti-Hebbian rules and appears to be mediated by associative depression at the synapses between parallel fibers and Purkinje-like cells of ELL. We show here that there is also a nonassociative potentiation at this synapse that depends only on the repeated occurrence of the EPSP. The depression can be reversed by the potentiation and vice versa. Finally, we show that the associative depression requires NMDA receptor activation, changes in postsynaptic calcium, and the occurrence of a postsynaptic dendritic spike within a few milliseconds following EPSP onset.     

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.     

Sensory expectations and anti-Hebbian synaptic plasticity in cerebellum-like structures

Cerebellum-like sensory structures in different groups of fish have been shown to generate a negative image of predictable features of the sensory input. We show here that anti-Hebbian plasticity is present at the synapse between parallel fibers and Purkinje-like cells which could mediate the generation of these negative images. We also show that this synapse is capable of bidirectional changes in synaptic efficacy with the direction of change depending on the precise temporal relation of presynaptic input and postsynaptic spike during pairing. Parallel fiber-evoked EPSPs are depressed after pairings in which the EPSP begins between 0 and 60 ms before the postsynaptic spike but are enhanced at other delays, including those in which the postsysnaptic spike occurs just before the EPSP.     

Timing actions to avoid refractoriness: a simple solution for streaming sensory signals

Segmenting self- from allo-generated signals is crucial for active sensory processing. We report a dynamic filter used by South American pulse electric fish to distinguish active electro-sensory signals carried by their own electric discharges from other concomitant electrical stimuli (i.e. communication signals). The filter has a sensory component, consisting of an onset type central electro-sensory neuron, and a motor component, consisting of a change in the fish's discharge rate when allo-generated electrical events occur in temporal proximity to the fish's own discharge. We investigated the sensory component of the filter by in vitro mimicking synaptic inputs occurring during behavioral responses to allo-generated interfering signals. We found that active control of the discharge enhances self-generated over allo-generated responses by forcing allo-generated signals into a central refractory period. This hypothesis was confirmed by field potential recordings in freely discharging fish. Similar sensory-motor mechanisms may also contribute to signal segmentation in other sensory systems.     

Stimulus-Timing Dependent Multisensory Plasticity in the Guinea Pig Dorsal Cochlear Nucleus

Multisensory neurons in the dorsal cochlear nucleus (DCN) show long-lasting enhancement or suppression of sound-evoked responses when stimulated with combined somatosensory-auditory stimulation. By varying the intervals between sound and somatosensory stimuli we show for the first time in vivo that DCN bimodal responses are influenced by stimulus-timing dependent plasticity. The timing rules and time courses of the observed stimulus-timing dependent plasticity closely mimic those of spike-timing dependent plasticity that have been demonstrated in vitro at parallel-fiber synapses onto DCN principal cells. Furthermore, the degree of inhibition in a neuron influences whether that neuron has Hebbian or anti-Hebbian timing rules. As demonstrated in other cerebellar-like circuits, anti-Hebbian timing rules reflect adaptive filtering, which in the DCN would result in suppression of sound-evoked responses that are predicted by activation of somatosensory inputs, leading to the suppression of body-generated signals such as self-vocalization.     

Omnidirectional sensory and motor volumes in electric fish

Active sensing organisms, such as bats, dolphins, and weakly electric fish, generate a 3-D space for active sensation by emitting self-generated energy into the environment. For a weakly electric fish, we demonstrate that the electrosensory space for prey detection has an unusual, omnidirectional shape. We compare this sensory volume with the animal's motor volume—the volume swept out by the body over selected time intervals and over the time it takes to come to a stop from typical hunting velocities. We find that the motor volume has a similar omnidirectional shape, which can be attributed to the fish's backward-swimming capabilities and body dynamics. We assessed the electrosensory space for prey detection by analyzing simulated changes in spiking activity of primary electrosensory afferents during empirically measured and synthetic prey capture trials. The animal's motor volume was reconstructed from video recordings of body motion during prey capture behavior. Our results suggest that in weakly electric fish, there is a close connection between the shape of the sensory and motor volumes. We consider three general spatial relationships between 3-D sensory and motor volumes in active and passive-sensing animals, and we examine hypotheses about these relationships in the context of the volumes we quantify for weakly electric fish. We propose that the ratio of the sensory volume to the motor volume provides insight into behavioral control strategies across all animals.     

Roles for short-term synaptic plasticity in behavior.

Short-term synaptic plasticity is phylogenetically widespread in ascending sensory systems of vertebrate brains. Such plasticity is found at all levels of sensory processing, including in sensory cortices. The functional roles of this apparently ubiquitous short-term synaptic plasticity, however, are not well understood. Data obtained in midbrain electrosensory neurons of Eigenmannia suggest that this plasticity has at least two roles in sensory processing; enhancing low-pass temporal filtering and generating phase shifts used in processing moving sensory images. Short-term synaptic plasticity may serve similar roles in other sensory modalities, including vision.     

Memory-based expectations in electrosensory systems

Adaptive processing of electrosensory information occurs in the cerebellum-like structures of three distinct groups of fish. Associations within each of these structures result in the generation of negative images of predictable features of the sensory inflow. Addition of these negative images to the actual inflow removes the predictable features, allowing the unpredictable, information-rich sensory signals to stand out. Evidence from all three groups of fish indicates that the negative images are mediated by plasticity at parallel fiber synapses.     

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.     

Functional origins of the vertebrate cerebellum from a sensory processing antecedent

The structure of the cerebellar cortex is remarkably similar across vertebrate phylogeny. It is well developed in basaljawed fishes, such as sharks and rays with many of the same cell types and organizational features found in other vertebrategroups, including mammals. In particular, the lattice-like organization of cerebellar cortex (with a molecular layer of parallel fibres,interneurons, spiny Purkinje cell dendrites, and climbing fires) is a common defining characteristic. In addition to the cerebell...     

Coactivation of pre- and postsynaptic signaling mechanisms determines cell-specific spike-timing-dependent plasticity

Synapses may undergo long-term increases or decreases in synaptic strength dependent on critical differences in the timing between pre-and postsynaptic activity. Such spike-timing-dependent plasticity (STDP) follows rules that govern how patterns of neural activity induce changes in synaptic strength. Synaptic plasticity in the dorsal cochlear nucleus (DCN) follows Hebbian and anti-Hebbian patterns in a cell-specific manner. Here we show that these opposing responses to synaptic activity result from differential expression of two signaling pathways. Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling underlies Hebbian postsynaptic LTP in principal cells. By contrast, in interneurons, a temporally precise anti-Hebbian synaptic spike-timing rule results from the combined effects of postsynaptic CaMKII-dependent LTP and endocannabinoid-dependent presynaptic LTD. Cell specificity in the circuit arises from selective targeting of presynaptic CB1 receptors in different axonal terminals. Hence, pre- and postsynaptic sites of expression determine both the sign and timing requirements of long-term plasticity in interneurons.     

Computational Consequences of Temporally Asymmetric Learning Rules: II. Sensory Image Cancellation

The electrosensory lateral line lobe (ELL) of mormyrid electric fish is a cerebellum-like structure that receives primary afferent input from electroreceptors in the skin. Purkinje-like cells in ELL store and retrieve a temporally precise negative image of prior sensory input. The stored image is derived from the association of centrally originating predictive signals with peripherally originating sensory input. The predictive signals are probably conveyed by parallel fibers. Recent in vitro experiments have demonstrated that pairing parallel fiber-evoked excitatory postsynaptic potentials (epsps) with postsynaptic spikes in Purkinje-like cells depresses the strength of these synapses. The depression has a tight dependence on the temporal order of pre- and postsynaptic events. The postsynaptic spike must follow the onset of the epsp within a window of about 60 msec for the depression to occur and pairings at other delays yield a nonassociative enhancement of the epsp. Mathematical analyses and computer simulations are used here to test the hypothesis that synaptic plasticity of the type established in vitro could be responsible for the storage of temporal patterns that is observed in vivo. This hypothesis is confirmed. The temporally asymmetric learning rule established in vitro results in the storage of activity patterns as observed in vivo and does so with significantly greater fidelity than other types of learning rules. The results demonstrate the importance of precise timing in pre- and postsynaptic activity for accurate storage of temporal information.     

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.     

Is there a thalamic component to experience-dependent cortical plasticity?

Sensory deprivation and injury to the peripheral nervous system both induce plasticity in the somatosensory system of adult animals, but in different places. While injury induces plasticity at several locations within the ascending somatosensory pathways, sensory deprivation appears only to affect the somatosensory cortex. Experiments have been performed to detect experience-dependent plasticity in thalamic receptive fields, thalamic domain sizes and convergence of thalamic receptive fields onto cortical cells. So far, plasticity has not been detected with sensory deprivation paradigms that cause substantial cortical plasticity. Part of the reason for the lack of thalamic plasticity may lie in the synaptic properties of afferent systems to the thalamus. A second factor may lie in the differences in the organization of cortical and thalamic circuits. Many deprivation paradigms induce plasticity by decreasing phasic lateral inhibition. Since lateral inhibition appears to be far weaker in the thalamus than the cortex, sensory deprivation may not cause large enough imbalances in thalamic activity to induce plasticity in the thalamus.     

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.     

Electric field interactions in pairs of electric fish: modeling and mimicking naturalistic inputs

Weakly electric fish acquire information about their surroundings by detecting and interpreting the spatial and temporal patterns of electric potential across their skin, caused by perturbations in a self-generated, oscillating electric field. Computational and experimental studies have focused on understanding the electric images due to simple, passive objects. The present study considers electric images of a conspecific fish. It is known that the electric fields of two fish interact to produce beats with spatially varying profiles of amplitude and phase. Such patterns have been shown to be critical for electrosensory-mediated behaviours, such as the jamming avoidance response, but they have yet to be well described. We have created a biophysically realistic model of a wave-type weakly electric fish by using a genetic algorithm to calibrate the parameters to the electric field of a real fish. We use the model to study a pair of fish and compute the electric images of one fish onto the other at three representative phases within a beat cycle. Analysis of the images reveals rostral/caudal and ipsilateral/contralateral patterns of amplitude and phase that have implications for localization of conspecifics (both position and orientation) and communication between conspecifics. We then show how the common stimulation paradigm used to mimic a conspecific during in vivo electrophysiological experiments, based on a transverse arrangement of two electrodes, can be improved in order to more accurately reflect the important qualitative features of naturalistic inputs, as revealed by our model.     

Electric images of two low resistance objects in weakly electric fish

Electroreceptive fish detect nearby objects by processing the information contained in the pattern of electric currents through their skin. In weakly electric fish, these currents arise from a self-generated field (the electric organ discharge), depending on the electrical properties of the surrounding medium. The electric image can be defined as the pattern of transepidermal voltage distributed over the receptive surface. To understand electrolocation it is necessary to know how electric image of objects are generated. In pulse mormyrids, the electric organ is localized at the tail, far from the receptors and fires a short biphasic pulse. Consequently, if all the elements in the environment are resistive, the stimulus at every point on the skin has the same waveform. Then, any measure of the amplitude (for example, the peak to peak amplitude) could be the unique parameter of the stimulus at any point of the skin. We have developed a model to calculate the image, corroborating that images are spread over the whole sensory surface and have an opposite center-surround, "Mexican-hat" shape. As a consequence, the images of different objects superimpose. We show theoretically and by simulation that the image of a pair of objects is not the simple addition of the individual images of these objects.     

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.     

A Developmental Switch for Hebbian Plasticity

Hebbian forms of synaptic plasticity are required for the orderly development of sensory circuits in the brain and are powerful modulators of learning and memory in adulthood. During development, emergence of Hebbian plasticity leads to formation of functional circuits. By modeling the dynamics of neurotransmitter release during early postnatal cortical development we show that a developmentally regulated switch in vesicle exocytosis mode triggers associative (i.e. Hebbian) plasticity. Early in development spontaneous vesicle exocytosis (SVE), often considered as ''synaptic noise'', is important for homogenization of synaptic weights and maintenance of synaptic weights in the appropriate dynamic range. Our results demonstrate that SVE has a permissive, whereas subsequent evoked vesicle exocytosis (EVE) has an instructive role in the expression of Hebbian plasticity. A timed onset for Hebbian plasticity can be achieved by switching from SVE to EVE and the balance between SVE and EVE can control the effective rate of Hebbian plasticity. We further show that this developmental switch in neurotransmitter release mode enables maturation of spike-timing dependent plasticity. A mis-timed or inadequate SVE to EVE switch may lead to malformation of brain networks thereby contributing to the etiology of neurodevelopmental disorders.