Biomedical subjects

Leonard Maler

Publications and source records attributed to Leonard Maler.

At least 19 recordsLinked to original sources

PubMed2005

A C-terminal domain directs Kv3.3 channels to dendrites.

Pyramidal neurons of the electrosensory lateral line lobe (ELL) of Apteronotus leptorhynchus express Kv3-type voltage-gated potassium channels that give rise to high-threshold currents at the somatic and dendritic levels. Two members of the Kv3 channel family, AptKv3.1 and AptKv3.3, are coexpressed in these neurons. AptKv3.3 channels are expressed at uniformly high levels in each of four ELL segments, whereas AptKv3.1 channels appear to be expressed in a graded manner with higher levels of expression in segments that process high-frequency electrosensory signals. Immunohistochemical and recombinant channel expression studies show a differential distribution of these two channels in the dendrites of ELL pyramidal neurons. AptKv3.1 is concentrated in somas and proximal dendrites, whereas AptKv3.3 is distributed throughout the full extent of the large dendritic tree. Recombinant channel expression of AptKv3 channels through in vivo viral injections allowed directed retargeting of AptKv3 subtypes over the somadendritic axis, revealing that the sequence responsible for targeting channels to distal dendrites lies within the C-terminal domain of the AptKv3.3 protein. The targeting domain includes a consensus sequence predicted to bind to a PDZ (postsynaptic density-95/Discs large/zona occludens-1)-type protein-protein interaction motif. These findings reveal that different functional roles for Kv3 potassium channels at the somatic and dendritic level of a sensory neuron are attained through specific targeting that selectively distributes Kv3.3 channels to the dendritic compartment.

Amino Acid Sequence↗

PubMed2005

Delayed excitatory and inhibitory feedback shape neural information transmission.

Feedback circuitry with conduction and synaptic delays is ubiquitous in the nervous system. Yet the effects of delayed feedback on sensory processing of natural signals are poorly understood. This study explores the consequences of delayed excitatory and inhibitory feedback inputs on the processing of sensory information. We show, through numerical simulations and theory, that excitatory and inhibitory feedback can alter the firing frequency response of stochastic neurons in opposite ways by creating dynamical resonances, which in turn lead to information resonances (i.e., increased information transfer for specific ranges of input frequencies). The resonances are created at the expense of decreased information transfer in other frequency ranges. Using linear response theory for stochastically firing neurons, we explain how feedback signals shape the neural transfer function for a single neuron as a function of network size. We also find that balanced excitatory and inhibitory feedback can further enhance information tuning while maintaining a constant mean firing rate. Finally, we apply this theory to in vivo experimental data from weakly electric fish in which the feedback loop can be opened. We show that it qualitatively predicts the observed effects of inhibitory feedback. Our study of feedback excitation and inhibition reveals a possible mechanism by which optimal processing may be achieved over selected frequency ranges.

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PubMed2005

Deterministic multiplicative gain control with active dendrites.

Multiplicative gain control is a vital component of many theoretical analyses of neural computations, conferring the ability to scale neuronal firing rate in response to synaptic inputs. Many theories of gain control in single cells have used precisely balanced noisy inputs. Such noisy inputs can degrade signal processing. We demonstrate a deterministic method for the control of gain without the use of noise. We show that a depolarizing afterpotential (DAP), arising from active dendritic spike backpropagation, leads to a multiplicative increase in gain. Reduction of DAP amplitude by dendritic inhibition dilutes the multiplicative effect, allowing for divisive scaling of the firing rate. In contrast, somatic inhibition acts in a subtractive manner, allowing spatially distinct inhibitory inputs to perform distinct computations. The simplicity of this mechanism and the ubiquity of its elementary components suggest that many cell types have the potential to display a dendritic division of neuronal output.

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PubMed2005

Feedback and feedforward control of frequency tuning to naturalistic stimuli.

Sensory neurons must respond to a wide variety of natural stimuli that can have very different spatiotemporal characteristics. Optimal responsiveness to subsets of these stimuli can be achieved by devoting specialized neural circuitry to different stimulus categories, or, alternatively, this circuitry can be modulated or tuned to optimize responsiveness to current stimulus conditions. This study explores the mechanisms that enable neurons within the initial processing station of the electrosensory system of weakly electric fish to shift their tuning properties based on the spatial extent of the stimulus. These neurons are tuned to low frequencies when the stimulus is restricted to a small region within the receptive field center but are tuned to higher frequencies when the stimulus impinges on large regions of the sensory epithelium. Through a combination of modeling and in vivo electrophysiology, we reveal the respective contributions of the filtering characteristics of extended dendritic structures and feedback circuitry to this shift in tuning. Our results show that low-frequency tuning can result from the cable properties of an extended dendrite that conveys receptor-afferent information to the cell body. The shift from low- to high-frequency tuning, seen in response to spatially extensive stimuli, results from increased wide-band input attributable to activation of larger populations of receptor afferents, as well as the activation of parallel fiber feedback from the cerebellum. This feedback provides a cancellation signal with low-pass characteristics that selectively attenuates low-frequency responsiveness. Thus, with spatially extensive stimuli, these cells preferentially respond to the higher-frequency components of the receptor-afferent input.

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PubMed2005

Electroreceptor neuron dynamics shape information transmission.

The gymnotiform weakly electric fish Apteronotus leptorhynchus can capture prey using electrosensory cues that are dominated by low temporal frequencies. However, conventional tuning curves predict poor electroreceptor afferent responses to low-frequency stimuli. We compared conventional tuning curves with information tuning curves and found that the latter predicted substantially improved responses to these behaviorally relevant stimuli. Analysis of receptor afferent baseline activity showed that negative correlations reduced low-frequency noise levels, thereby increasing information transmission. Multiunit recordings from receptor afferents showed that this increased information transmission could persist at the population level. Finally, we verified that this increased low-frequency information is preserved in the spike trains of central neurons that receive receptor afferent input. Our results demonstrate that conventional tuning curves can be misleading when certain noise reduction strategies are used by the nervous system.

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PubMed2004

Oscillatory activity in electrosensory neurons increases with the spatial correlation of the stochastic input stimulus.

We present results from a novel experimental paradigm to investigate the influence of spatial correlations of stimuli on electrosensory neural network dynamics. Further, a new theoretical analysis for the dynamics of a model network of stochastic leaky integrate-and-fire neurons with delayed feedback is proposed. Experiment and theory for this system both establish that spatial correlations induce a network oscillation, the strength of which is proportional to the degree of stimulus correlation at constant total stimulus power.

Animals↗

PubMed2004

Parallel processing of sensory input by bursts and isolated spikes.

Burst firing is commonly observed in many sensory systems and is proposed to transmit information reliably. Although a number of biophysical burst mechanisms have been identified, the relationship between burst dynamics and information transfer is uncertain. Electrosensory pyramidal cells have a well defined backpropagation-dependent burst mechanism. We used in vivo, in vitro, and modeling approaches to investigate pyramidal cell responses to mimics of behaviorally relevant sensory input. We found that within a given spike train, bursts are biased toward low-frequency events while isolated spikes simultaneously code for the entire frequency range. We also demonstrated that burst dynamics are essential for optimal feature detection but are not required for stimulus estimation. We conclude that burst and spike dynamics can segregate a single spike train into two parallel and complementary streams of information transfer.

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PubMed2004

Plastic and nonplastic pyramidal cells perform unique roles in a network capable of adaptive redundancy reduction.

Pyramidal cells show marked variation in their morphology, including dendritic structure, which is correlated with physiological diversity; however, it is not known how this variation is related to a cell's role within neural networks. In this report, we describe correlations among electrosensory lateral line lobe (ELL) pyramidal cells' highly variable dendritic morphology and their ability to adaptively cancel redundant inputs via an anti-Hebbian form of synaptic plasticity. A subset of cells, those with the largest apical dendrites, are plastic, but those with the smallest dendrites are not. A model of the network's connectivity predicts that efficient redundancy reduction requires that nonplastic cells provide feedback input to those that are plastic. Anatomical results confirm the model's prediction of optimal network architecture. These results provide a demonstration of different roles for morphological/physiological variants of a single cell type within a neural network performing a well-defined function.

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PubMed2003

Synaptic dynamics on different time scales in a parallel fiber feedback pathway of the weakly electric fish.

Synaptic dynamics comprise a variety of interacting processes acting on a wide range of time scales. This enables a synapse to perform a large array of computations, from temporal and spatial filtering to associative learning. In this study, we describe how changing synaptic gain via long-term plasticity can act to shape the temporal filtering of a synapse through modulation of short-term plasticity. In the weakly electric fish, parallel fibers from cerebellar granule cells provide massive feedback inputs to the pyramidal neurons of the electrosensory lateral line lobe. We demonstrate a long-term synaptic enhancement (LTE) of these synapses that is biochemically similar to the presynaptic long-term potentiation expressed by parallel fibers in the mammalian cerebellum. Using a novel stimulation protocol and a simple modeling paradigm, we then quantify the changes in short-term plasticity during the induction of LTE and show that these changes can be explained by gradual changes in only one model parameter, that which is associated with the baseline probability of transmitter release. These changes lead to a shift in the spike frequency preference of the synapse, suggesting that long-term plasticity is not only involved in controlling the gain of the parallel fiber synapse, but also provides a means of controlling synaptic filtering over multiple time scales.

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PubMed2003

Non-classical receptive field mediates switch in a sensory neuron's frequency tuning.

Animals have developed stereotyped communication calls to which specific sensory neurons are well tuned. These communication calls must be discriminated from environmental signals such as those produced by prey. Sensory systems might have evolved neural circuitry to encode both categories. In weakly electric fish, prey and communication signals differ in their spatial extent and frequency content. Here we show that stimuli of different spatial extents mimicking prey and communication signals cause a switch in the frequency tuning and spike-timing precision of electrosensory pyramidal neurons, resulting in the selective and optimal encoding of both stimulus categories. As in other sensory systems, pyramidal neurons respond only to stimuli located within a restricted region of space known as the classical receptive field (CRF). In some systems, stimulation outside the CRF but within a non-classical receptive field (nCRF) can modulate the neural response to CRF stimulation even though nCRF stimulation alone fails to elicit responses. We show that pyramidal neurons possess a nCRF and that it can modulate the response to CRF stimuli to induce this neurobiological switch in frequency tuning.

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PubMed2003

Inhibitory feedback required for network oscillatory responses to communication but not prey stimuli.

Stimulus-induced oscillations occur in visual, olfactory and somatosensory systems. Several experimental and theoretical studies have shown how such oscillations can be generated by inhibitory connections between neurons. But the effects of realistic spatiotemporal sensory input on oscillatory network dynamics and the overall functional roles of such oscillations in sensory processing are poorly understood. Weakly electric fish must detect electric field modulations produced by both prey (spatially localized) and communication (spatially diffuse) signals. Here we show, through in vivo recordings, that sensory pyramidal neurons in these animals produce an oscillatory response to communication-like stimuli, but not to prey-like stimuli. On the basis of well-characterized circuitry, we construct a network model of pyramidal neurons that predicts that diffuse delayed inhibitory feedback is required to achieve oscillatory behaviour only in response to communication-like stimuli. This prediction is experimentally verified by reversible blockade of feedback inhibition that removes oscillatory behaviour in the presence of communication-like stimuli. Our results show that a sensory system can use inhibitory feedback as a mechanism to 'toggle' between oscillatory and non-oscillatory firing states, each associated with a naturalistic stimulus.

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PubMed2003

The effects of spontaneous activity, background noise, and the stimulus ensemble on information transfer in neurons.

Information theory is playing an increasingly important role in the analysis of neural data as it can precisely quantify the reliability of stimulus-response functions. Estimating the mutual information between a neural spike train and a time varying stimulus is, however, not trivial in practice and requires assumptions about the specific computations being performed by the neuron under study. Consequently, estimates of the mutual information depend on these assumptions and their validity must be ascertained in the particular physiological context in which experiments are carried out. Here we compare results obtained using different information measures that make different assumptions about the neural code (i.e. the way information is being encoded and decoded) and the stimulus ensemble (i.e. the set of stimuli that the animal can encounter in nature). Our comparisons are carried out in the context of spontaneously active neurons. However, some of our results are also applicable to neurons that are not spontaneously active. We first show conditions under which a single stimulus provides a good sample of the entire stimulus ensemble. Furthermore, we use a recently introduced information measure that is based on the spontaneous activity of the neuron rather than on the stimulus ensemble. This measure is compared to the Shannon information and it is shown that the two differ only by a constant. This constant is shown to represent the information that the neuron's spontaneous activity transmits about the fact that no stimulus is present in the animal's environment. As a consequence, the mutual information measure based on spontaneous activity is easily applied to stimuli that mimic those seen in nature, as it does not require a priori knowledge of the stimulus ensemble. Finally, we consider the effect of noise in the animal's environment on information transmission about sensory stimuli. Our results show that, as expected, such 'background' noise will increase the trial-to-trial variability of the neural response to repeated presentations of a stimulus. However, the same background noise can also increase the variability of the spike train and hence can lead to increased information transfer in the presence of background noise. Our study emphasizes how different assumptions can lead to different predictions for the information transmission of a neuron. Assumptions about the computations being performed by the system under study as well as the stimulus ensemble and background noise should therefore be carefully considered when applying information theory.

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PubMed2002

Receptive field organization determines pyramidal cell stimulus-encoding capability and spatial stimulus selectivity.

Sensory systems must operate over a wide range of spatial scales, and single neuron receptive field (RF) organization may contribute to the ability of a neuron to encode information about stimuli having different spatial characteristics. Here we relate the RF organization of sensory neurons to their ability to encode time-varying stimuli, using linear stimulus estimation, measures of information transfer, and more conventional analysis techniques. The electrosensory systems of weakly electric fish are recognized as very tractable model systems for studies of sensory processing because behaviorally relevant stimuli are generated easily and related to known behaviors and because a detailed anatomical database is available to guide the design and interpretation of experiments. Receptive fields of neurons within the first central electrosensory-processing region have an antagonistic center-surround organization; the RF area varies with cell type, with dendritic morphology, and with the spontaneous activity patterns of the cell. Functional consequences of variations in center-surround organization were assessed by comparing responses to two spatial stimulus patterns that mimic naturalistic stimuli and that provide input to the center alone or to the center plus surround. Measures of the quality of stimulus estimation (coding fraction) and information transmission (mutual information) as well as traditional measures of responsiveness consistently demonstrate that, for cells having large surrounds, the activation of both receptive field components degrades the ability to encode time-varying stimuli. The loss of coding efficiency with center-surround stimulation probably results from cancellation of balanced excitatory and inhibitory inputs. However, cells with small surrounds relative to centers perform well under all spatial stimulus regimes.

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PubMed2002

Dynamically interacting processes underlie synaptic plasticity in a feedback pathway.

Descending feedback is a common feature of sensory systems. Characterizing synaptic plasticity in feedback inputs is essential for delineating the role of feedback in sensory processing. In this study, we demonstrate that multiple interacting processes underlie the dynamics of synaptic potentiation in one such sensory feedback pathway. We use field recording and modeling to investigate the interaction between the transient high-magnitude potentiation (200-300%) elicited during tetanic stimulation of the feedback pathway and the lower magnitude posttetanic potentiation (PTP; ~30%) that slowly decays on cessation of the tetanus. The amplitude of the observed transient potentiation is graded with stimulus frequency. In contrast, the induction of PTP has a stimulus frequency threshold between 1 and 5 Hz, and its amplitude is independent of stimulus frequency. We suggest that the threshold for PTP induction may be linked to a minimum level of sustained potentiation (MSP) during repetitive trains of stimuli. We have developed a novel model that describes the interaction between the transient plasticity observed during train stimulation and the generation of PTP. The model combines a multiplicative, facilitation-depression-type (FD) model that describes the transient plasticity, with an enzymatic network that describes the dynamics of PTP. The model links transient plasticity to PTP through an input term that reflects MSP. The stratum fibrosum-pyramidal cell (StF-PC) synapse investigated in this study is the terminus of a feedback pathway to the electrosensory lateral line lobe (ELL) of a weakly electric gymnotiform fish. Dynamic plasticity at the StF-PC synapse may contribute to the putative role of this feedback pathway as a sensory searchlight.

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PubMed2002

Dynamics of electrosensory feedback: short-term plasticity and inhibition in a parallel fiber pathway.

The dynamics of neuronal feedback pathways are generally not well understood. This is due to the complexity arising from the combined dynamics of closed-loop feedback systems and the synaptic plasticity of feedback connections. Here, we investigate the short-term synaptic dynamics underlying the parallel fiber feedback pathway to a primary electrosensory nucleus in the weakly electric fish, Apteronotus leptorhynchus. In open-loop conditions, the dynamics of this pathway arise from a monosynaptic excitatory connection and a disynaptic (feed-forward) inhibitory connection to pyramidal neurons in the electrosensory lateral line lobe (ELL). In a brain slice preparation of the ELL, we characterized the synaptic responses of pyramidal neurons to short trains of electrical stimuli delivered to the parallel fibers of the dorsal molecular layer. Stimulus trains consisted of 20 pulses, at either random intervals or constant intervals, with varying mean frequencies. With random trains, pyramidal neuron responses were well described by a single exponential function of the inter-stimulus interval-suggesting a single facilitation-like process underlies these synaptic dynamics. However, responses to periodic (constant interval) trains deviated from this simple description. Random and periodic stimulus trains delivered when the feed-forward inhibitory component of this pathway was pharmacologically blocked revealed that inhibition and depression also contribute to the observed dynamics. We formulated a simple model of the parallel fiber synaptic dynamics that provided an accurate description of our data. The model dynamics resulted from a combination of three distinct processes. Two of the processes are the classically-described synaptic facilitation and depression, and the third is a novel description of feed-forward inhibition. An analysis of this model suggests that synaptic pathways combining plasticity with feed-forward inhibition can be easily tuned to signal different types of transient stimuli and thus lead to diverse and nonintuitive filtering properties.

Animals↗

PubMedDate not supplied

Oscillatory burst discharge generated through conditional backpropagation of dendritic spikes.

Gamma frequencies of burst discharge (>40 Hz) have become recognized in select cortical and non-cortical regions as being important in feature extraction, neural synchrony and oscillatory discharge. Pyramidal cells of the electrosensory lateral line lobe (ELL) of Apteronotus leptorhynchus generate burst discharge in relation to specific features of sensory input in vivo that resemble those recognized as gamma frequency discharge when examined in vitro. We have shown that these bursts are generated by an entirely novel mechanism termed conditional backpropagation that involves an intermittent failure of dendritic Na+ spike conduction. Conditional backpropagation arises from a frequency-dependent broadening of dendritic spikes during repetitive discharge, and a mismatch between the refractory periods of somatic and dendritic spikes. A high threshold class of K+ channel, AptKv3.3, is expressed at high levels and distributed over the entire soma-dendritic axis of pyramidal cells. AptKv3.3 channels are shown to contribute to the repolarization of both somatic and dendritic spikes, with pharmacological blockade of dendritic Kv3 channels revealing an important role in controlling the threshold for burst discharge. The entire process of conditional back-propagation and burst output is successfully simulated using a new compartmental model of pyramidal cells that incorporates a cumulative inactivation of dendritic K+ channels during repetitive discharge. This work is important in demonstrating how the success of spike backpropagation can control the output of a principle sensory neuron, and how this process is regulated by the distribution and properties of voltage-dependent K+ channels.

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PubMedDate not supplied

Ghostbursting: a novel neuronal burst mechanism.

Pyramidal cells in the electrosensory lateral line lobe (ELL) of weakly electric fish have been observed to produce high-frequency burst discharge with constant depolarizing current (Turner et al., 1994). We present a two-compartment model of an ELL pyramidal cell that produces burst discharges similar to those seen in experiments. The burst mechanism involves a slowly changing interaction between the somatic and dendritic action potentials. Burst termination occurs when the trajectory of the system is reinjected in phase space near the "ghost" of a saddle-node bifurcation of fixed points. The burst trajectory reinjection is studied using quasi-static bifurcation theory, that shows a period doubling transition in the fast subsystem as the cause of burst termination. As the applied depolarization is increased, the model exhibits first resting, then tonic firing, and finally chaotic bursting behavior, in contrast with many other burst models. The transition between tonic firing and burst firing is due to a saddle-node bifurcation of limit cycles. Analysis of this bifurcation shows that the route to chaos in these neurons is type I intermittency, and we present experimental analysis of ELL pyramidal cell burst trains that support this model prediction. By varying parameters in a way that changes the positions of both saddle-node bifurcations in parameter space, we produce a wide gallery of burst patterns, which span a significant range of burst time scales.

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PubMedDate not supplied

Type I burst excitability.

We introduce the concept of "type I burst excitability", which is a generalization of the "normal" excitability that is well-known in cardiac and neural systems. We demonstrate this type of burst excitability in a specific model system, a pyramidal cell from the electrosensory lateral line lobe of the weakly electric fish Apteronotus leptorhynchus. As depolarizing current is increased, a saddle-node bifurcation of periodic orbits occurs, which separates tonic and burst activity. This bifurcation is responsible for the excitable nature of the system, and is the basis for the "type I" designation. We verify the existence of this transition from in vitro recordings of a number of actual pyramidal cells. A scaling relationship between the magnitude and duration of a current pulse required to induce a burst is derived. We also observe this type of burst excitability and the scaling relationships in a multicompartmental model that is driven by realistic stochastic synaptic inputs mimicking sensory input. We conclude by discussing the relevance of burst excitability to communication between weakly electric fish.

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