Curtis C. Bell

Cerebellum-Like Structures and Their Implications for Cerebellar Function

The nervous systems of most vertebrates include both the cerebellum and structures that are architecturally similar to the cerebellum. The cerebellum-like structures are sensory structures that receive input from the periphery in their deep layers and parallel fiber input in their molecular layers. This review describes these cerebellum-like structures and compares them with the cerebellum itself. The cerebellum-like structures in three groups of fish act as adaptive sensory processors in which the signals conveyed by parallel fibers in the molecular layer predict the patterns of sensory input to the deep layers through a process of associative synaptic plasticity. Similarities between the cerebellum-like structures and the cerebellum suggest that the cerebellum may also generate predictions about expected sensory inputs or states of the system, as suggested also by clinical, experimental, and theoretical studies of the cerebellum. Understanding the process of predicting sensory patterns in cerebellum-like structures may therefore be a source of insight into cerebellar function.

Spike timing dependent synaptic plasticity in biological systems

Abstract.u2002Association of a presynaptic spike with a postsynaptic spike can lead to changes in synaptic efficacy that are highly dependent on the relative timing of the pre- and postsynaptic spikes. Different synapses show varying forms of such spike-timing dependent learning rules. This review describes these different rules, the cellular mechanisms that may be responsible for them, and the computational consequences of these rules for information processing and storage in the nervous system.

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.

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.

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.

Evolution of Cerebellum-Like Structures

All vertebrate brains have a cerebellum, and most of them have one or more additional structures that are histologically similar to the cerebellum. The cerebellum-like structures include the medial octavolateral nucleus in most aquatic vertebrates; the dorsal octavolateral nucleus in many aquatic vertebrates with an electrosensory system; the marginal layer of the optic tectum in ray-finned fishes; electrosensory lobes in the few groups of advanced bony fish with an electrosensory system; the rostrolateral nucleus of the thalamus in a few widely scattered groups of bony fish; and the dorsal cochlear nucleus in all mammals except monotremes. All of these structures receive topographically organized sensory input in their deep layers. Purkinje-like cells receive the sensory input near their cell bodies. These cells extend apical dendrites up into the molecular layer where they receive synaptic input from parallel fibers. The cerebellum itself can be included within this characterization by considering the climbing fiber as at least in part a conveyor of sensory information and by recalling that climbing fibers in more basal vertebrates terminate on smooth dendrites close to the soma. Physiological findings from three different systems suggest the hypothesis that cerebellum-like structures remove predictable features from the sensory inflow. Phylogenetic homology can explain the similarities across different taxa for some types of cerebellum-like structures, but similarities within other types cannot be explained in this way. Moreover, phylogenetic homology cannot explain the similarities among different types of cerebellum-like structures. Evolutionary convergence provides the best explanation for all these similarities that cannot be explained by homology. The convergence is almost surely constrained by the availability of a genetic-developmental program for creating cerebellum-like circuitry and by the need within many different systems for the type of information processing that cerebellum-like circuitry can provide.

The Mormyrid Electrosensory Lobe In Vitro: Physiology and Pharmacology of Cells and Circuits

This paper is concerned with the electrosensory lobe (ELL) of mormyrid electric fish as examined in in vitro slices. Intracellular recordings from morphologically identified cells and field potential recordings were used to characterize the physiology and pharmacology of ELL cells. Most intracellular recordings were from the Purkinje-like interneurons that are known as medium ganglion cells and from the two types of efferent neurons, large ganglion and large fusiform cells. Stimulation of primary afferent fibers elicits both excitatory and inhibitory effects in these cells, with the excitatory effects being mediated by both the AMPA and NMDA types of glutamate receptors and the inhibitory effects being mediated by both GABAA and glycine receptors. Parallel-fiber stimulation evokes an EPSP–IPSP sequence, with the EPSPs being mediated by both AMPA and NMDA receptors and the IPSPs being mediated by GABAA receptors only. The parallel fiber-evoked EPSPs and IPSPs show marked paired-pulse facilitation. A large and unusually broad spike is recorded inside medium ganglion cells, and field potential responses suggest that this spike is propagated into the apical dendrites. The results provide essential information for understanding how peripheral and central inputs are integrated in ELL.

Central Control of Dendritic Spikes Shapes the Responses of Purkinje-Like Cells through Spike Timing-Dependent Synaptic Plasticity

Cerebellum-like structures process peripheral sensory information in combination with parallel fiber inputs that convey information about sensory and motor contexts. Activity-dependent changes in the strength of parallel fiber synapses act as an adaptive filter, removing predictable features of the sensory input. In the electrosensory lobe (ELL) of mormyrid fish, a main cellular site for this adaptive processing is the Purkinje-like medium ganglion (MG) cell. MG cells exhibit two types of spikes: narrow axon spikes (N spikes) and broad dendritic spikes (B spikes). N spikes shape ELL output by inhibiting efferent cells, whereas B spikes drive plasticity at parallel fiber synapses. Despite their critical role in plasticity, little is known about the relative importance of various classes of MG cell inputs in driving B spikes or to what extent B spikes can be controlled independently of N spikes. Using in vivo intracellular recordings, measurements of synaptic conductance, and pharmacological blockade of inhibition, we provide evidence for corollary discharge-evoked inhibition that exerts potent control over the timing and probability of B spikes with little apparent effect on N spikes. The timing of this inhibition corresponds to the period during which repeated occurrence of B spikes causes depression of corollary discharge-evoked synaptic responses and a reduction in N spikes. B spikes occurring before or after the period of inhibition lead to increases in corollary discharge-evoked excitation. Thus, by controlling the timing of B spikes, central inhibition shapes the output of MG cells through spike timing-dependent synaptic plasticity. Our findings are consistent with a model of ELL function in which feedback guides adaptive processing by regulating B spikes.

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.

Immunocytochemical identification of cell types in the mormyrid electrosensory lobe

The electrosensory lobes (ELLs) of mormyrid and gymnotid fish are useful sites for studying plasticity and descending control of sensory processing. This study used immunocytochemistry to examine the functional circuitry of the mormyrid ELL. We used antibodies against the following proteins and amino acids: the neurotransmitters glutamate and γ‐aminobutyric acid (GABA); the GABA‐synthesizing enzyme glutamic acid decarboxylase (GAD); GABA transporter 1; the anchoring protein for GABA and glycine receptors, gephyrin; the calcium binding proteins calbindin and calretinin; the NR1 subunit of the N‐methyl‐D‐aspartate glutamate receptor; the metabotropic glutamate receptors mGluR1α, mGluR2/3, and mGluR5; and the intracellular signaling molecules calcineurin, calcium calmodulin kinase IIα (CAMKIIα) and the receptor for inositol triphosphate (IP3R1α). Selective staining allowed for identification of new cell types including a deep granular layer cell that relays sensory information from primary afferent fibers to higher order cells of ELLS. Selective staining also allowed for estimates of relative numbers of different cell types. Dendritic staining of Purkinje‐like medium ganglion cells with antibodies against metabotropic glutamate receptors and calcineurin suggests hypotheses concerning mechanisms of the previously demonstrated synaptic plasticity in these cells. Finally, several cell types including the above‐mentioned granular cells, thick‐smooth dendrite cells, and large multipolar cells of the intermediate layer were present in the two zones of ELL that receive input from mormyromast electroreceptors but were absent in the zone of ELL that receives input from ampullary electroreceptors, indicating markedly different processing for these two types of input. J. Comp. Neurol. 483:124–142, 2005.