Electrosensory Lateral Line Lobe Pyramidal Cells Research Articles

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.

Analysis of the electrosensory pyramidal cell bursting model for weakly electric fish: Model prediction under low levels of dendritic potassium conductance

Pyramidal cells in the electrosensory lateral line lobe (ELL) of weakly electric fish produce burst discharge. A Hodgkin-Huxley-type model, called ghostburster, consisting of two compartments (soma and dendrite) reproduces ELL pyramidal cell bursting observed in vitro. A previous study analyzed the ghostburster by treating Is and gDr,d as bifurcation parameters (Is: current injected into the somatic compartment and gDr,d: maximal conductance of the delayed rectifying potassium current in the dendritic compartment) and indicated that when both Is and gDr,d are set at particular values, the ghostburster shows a codimension-two bifurcation at which both saddle-node bifurcation of fixed points and saddle-node bifurcation of limit cycles occur simultaneously. In the present study, the ghostburster was investigated to clarify the bursting that occurred at gDr,d values smaller than that at the codimension-two bifurcation. Based on the number of spikes per burst, various burst patterns were observed depending on the (Is, gDr,d) values. Depending on the (Is, gDr,d) values, the burst trajectory in a phase space of the ghostburster showed either a high or a low degree of periodicity. Compared to the previous study, the present findings contribute to a more detailed understanding of ghostburster bursting.

Neural Heterogeneity and Efficient Population Codes for Communication Signals

Efficient sensory coding implies that populations of neurons should represent information-rich aspects of a signal with little redundancy. Recent studies have shown that neural heterogeneity in higher brain areas enhances the efficiency of encoding by reducing redundancy across the population. Here, we study how neural heterogeneity in the early stages of sensory processing influences the efficiency of population codes. Through the analysis of in vivo recordings, we contrast the encoding of two types of communication signals of electric fishes in the most peripheral sensory area of the CNS, the electrosensory lateral line lobe (ELL). We show that communication signals used during courtship (big chirps) and during aggressive encounters (small chirps) are encoded by different populations of ELL pyramidal cells, namely I-cells and E-cells, respectively. Most importantly, we show that the encoding strategy differs for the two signals and we argue that these differences allow these cell types to encode specifically information-rich features of the signals. Small chirps are detected, and their timing is accurately signaled through stereotyped spike bursts, whereas the shape of big chirps is accurately represented by variable increases in firing rate. Furthermore, we show that the heterogeneity across I-cells enhances the efficiency of the population code and thus permits the accurate discrimination of different quality courtship signals. Our study shows the importance of neural heterogeneity early in a sensory system and that it initiates the sparsification of sensory representation thereby contributing to the efficiency of the neural code.

Burst-Induced Anti-Hebbian Depression Acts through Short-Term Synaptic Dynamics to Cancel Redundant Sensory Signals

Weakly electric fish can enhance the detection and localization of important signals such as those of prey in part by cancellation of redundant spatially diffuse electric signals due to, e.g., their tail bending. The cancellation mechanism is based on descending input, conveyed by parallel fibers emanating from cerebellar granule cells, that produces a negative image of the global low-frequency signals in pyramidal cells within the first-order electrosensory region, the electrosensory lateral line lobe (ELL). Here we demonstrate that the parallel fiber synaptic input to ELL pyramidal cell undergoes long-term depression (LTD) whenever both parallel fiber afferents and their target cells are stimulated to produce paired burst discharges. Paired large bursts (4-4) induce robust LTD over pre-post delays of up to +/-50 ms, whereas smaller bursts (2-2) induce weaker LTD. Single spikes (either presynaptic or postsynaptic) paired with bursts did not induce LTD. Tetanic presynaptic stimulation was also ineffective in inducing LTD. Thus, we have demonstrated a form of anti-Hebbian LTD that depends on the temporal correlation of burst discharge. We then demonstrated that the burst-induced LTD is postsynaptic and requires the NR2B subunit of the NMDA receptor, elevation of postsynaptic Ca(2+), and activation of CaMKIIbeta. A model incorporating local inhibitory circuitry and previously identified short-term presynaptic potentiation of the parallel fiber synapses further suggests that the combination of burst-induced LTD, presynaptic potentiation, and local inhibition may be sufficient to explain the generation of the negative image and cancellation of redundant sensory input by ELL pyramidal cells.

Neural heterogeneities and stimulus properties affect burst coding in vivo

Many neurons tend to fire clusters of action potentials called bursts followed by quiescence in response to sensory input. While the mechanisms that underlie burst firing are generally well understood in vitro, the functional role of these bursts in generating behavioral responses to sensory input in vivo are less clear. Pyramidal cells within the electrosensory lateral line lobe (ELL) of weakly electric fish offer an attractive model system for studying the coding properties of burst firing, because the anatomy and physiology of the electrosensory circuitry are well understood, and the burst mechanism of ELL pyramidal cells has been thoroughly characterized in vitro. We investigated the coding properties of bursts generated by these cells in vivo in response to mimics of behaviorally relevant sensory input. We found that heterogeneities within the pyramidal cell population had quantitative but not qualitative effects on burst coding for the low frequency components of broadband time varying input. Moreover, spatially localized stimuli mimicking, for example, prey tended to elicit more bursts than spatially global stimuli mimicking conspecific-related stimuli. We also found small but significant correlations between burst attributes such as the number of spikes per burst or the interspike interval during the burst and stimulus attributes such as stimulus amplitude or slope. These correlations were much weaker in magnitude than those observed in vitro. More surprisingly, our results show that correlations between burst and stimulus attributes actually decreased in magnitude when we used low frequency stimuli that are expected to promote burst firing. We propose that this discrepancy is attributable to differences between ELL pyramidal cell burst firing under in vivo and in vitro conditions.

Regulated expression of N‐methyl‐D‐aspartate receptors and associated proteins in teleost electrosensory system and telencephalon

Several types of N-methyl-D-aspartate (NMDA) receptor-dependent synaptic plasticity are characterized by differences in polarity, induction parameters, and duration, which depend on the interactions of NMDARs with intracellular synaptic and signaling proteins. Here, we examine the NMDAR signaling components in the brain of the weakly electric fish Apteronotus leptorhynchus. Compared with mammalian orthologs, high levels of sequence conservation for known functional sites in both NMDAR subunits (NR1, NR2A-C) and signaling proteins (fyn tyrosine kinase, RasGRF-1 and -2) were found. In situ hybridization analysis demonstrated that, similar to the case in the adult mammal brain, NR2A and NR2B are expressed at moderate levels in most brain regions and at very high levels in the dorsal telencephalon. RasGRF-1 and fyn have a similar distribution and appear to be coexpressed with NR2B in telencephalic regions known to support learning and long-term memory. Both NR2A and NR2B are highly expressed in pyramidal cells of the electrosensory lateral line lobe (ELL) known to exhibit the short-term synaptic plasticity that underlies adaptive feedback cancellation of redundant sensory input. In contrast, nonplastic pyramidal cells expressed only the NR2A subunit. Furthermore, field recordings show that ifenprodil-sensitive NR2B-containing NMDARs predominate for the plastic feedback input to ELL pyramidal cells. However, RasGRF-1 and fyn are expressed only at low levels in a subset of these pyramidal cells. Our data suggest that NMDAR functions are highly conserved between fish and mammals and that synaptic plasticity dynamics in different brain regions are related to the expression patterns of the synaptic signaling proteins interacting with NMDARs.

Interval Coding. II. Dendrite-Dependent Mechanisms

The rich temporal structure of neural spike trains provides multiple dimensions to code dynamic stimuli. Popular examples are spike trains from sensory cells where bursts and isolated spikes can serve distinct coding roles. In contrast to analyses of neural coding, the cellular mechanics of burst mechanisms are typically elucidated from the neural response to static input. Bridging the mechanics of bursting with coding of dynamic stimuli is an important step in establishing theories of neural coding. Electrosensory lateral line lobe (ELL) pyramidal neurons respond to static inputs with a complex dendrite-dependent burst mechanism. Here we show that in response to dynamic broadband stimuli, these bursts lack some of the electrophysiological characteristics observed in response to static inputs. A simple leaky integrate-and-fire (LIF)-style model with a dendrite-dependent depolarizing afterpotential (DAP) is sufficient to match both the output statistics and coding performance of experimental spike trains. We use this model to investigate a simplification of interval coding where the burst interspike interval (ISI) codes for the scale of a canonical upstroke rather than a multidimensional stimulus feature. Using this stimulus reduction, we compute a quantization of the burst ISIs and the upstroke scale to show that the mutual information rate of the interval code is maximized at a moderate DAP amplitude. The combination of a reduced description of ELL pyramidal cell bursting and a simplification of the interval code increases the generality of ELL burst codes to other sensory modalities.

Pings the Body Electric (and Means It Too). Focus on “Interval Coding. I. Burst Interspike Intervals as Indicators of Stimulus Intensity” and “Interval Coding. II. Dendrite-Dependent Mechanisms”

Structure/function questions are at the forefront of research in biological sensory systems. These questions are very elegantly addressed by Oswald et al. and Doiron et al. in a pair of articles on signal representation in electric fish in this issue of Journal of Neurophysiology (p. 2731–2743 and

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.

Function of NMDA receptors and persistent sodium channels in a feedback pathway of the electrosensory system.

Voltage-dependent amplification of ionotropic glutamatergic excitatory postsynaptic potentials (EPSPs) can, in many vertebrate neurons, be due either to the intrinsic voltage dependence of N-methyl-D-aspartate (NMDA) receptors, or voltage-dependent persistent sodium channels expressed on postsynaptic dendrites or somata. In the electrosensory lateral line lobe (ELL) of the gymnotiform fish Apteronotus leptorhynchus, glutamatergic inputs onto pyramidal cell apical dendrites provide a system where both amplification mechanisms are possible. We have now examined the roles for both NMDA receptors and sodium channels in the control of EPSP amplitude at these synapses. An antibody specific for the A. leptorhynchus NR1 subunit reacted strongly with ELL pyramidal cells and were particularly abundant in the spines of pyramidal cell apical dendrites. We have also shown that NMDA receptors contributed strongly to the late phase of EPSPs evoked by stimulation of the feedback fibers terminating on the apical dendritic spines; further, these EPSPs were voltage dependent. Blockade of NMDA receptors did not, however, eliminate the voltage dependence of these EPSPs. Blockade of somatic sodium channels by local somatic ejection of tetrodotoxin (TTX), or inclusion of QX314 (an intracellular sodium channel blocker) in the recording pipette, reduced the evoked EPSPs and completely eliminated their voltage dependence. We therefore conclude that, in the subthreshold range, persistent sodium currents are the main contributor to voltage-dependent boosting of EPSPs, even when they have a large NMDA receptor component.

Dendritic modulation of burst-like firing in sensory neurons.

This report describes the variability of spontaneous firing characteristics of sensory neurons, electrosensory lateral line lobe (ELL) pyramidal cells, within the electrosensory lateral line lobe of weakly electric fish in vivo. We show that these cells' spontaneous firing frequency, measures of spike train regularity (interspike interval coefficient of variation), and the tendency of these cells to produce bursts of action potentials are correlated with the size of the cell's apical dendritic arbor. We also show that bursting behavior may be influenced or controlled by descending inputs from higher centers that provide excitatory and inhibitory inputs to the pyramidal cells' apical dendrites. Pyramidal cells were classified as "bursty" or "nonbursty" according to whether or not spike trains deviated significantly from the expected properties of random (Poisson) spike trains of the same average firing frequency, and, in the case of bursty cells, the maximum within-burst interspike interval characteristic of bursts was determined. Each cell's probability of producing bursts above the level expected for a Poisson spike train was determined and related to spontaneous firing frequency and dendritic morphology. Pyramidal cells with large apical dendritic arbors have lower rates of spontaneous activity and higher probabilities of producing bursts above the expected level, while cells with smaller apical dendrites fire at higher frequencies and are less bursty. The effect of blocking non-N-methyl-D-aspartate (non-NMDA) glutamatergic synaptic inputs to the apical dendrites of these cells, and to local inhibitory interneurons, significantly reduced the spontaneous occurrence of spike bursts and intracellular injection of hyperpolarizing current mimicked this effect. The results suggest that bursty firing of ELL pyramidal cells may be under descending control allowing activity in electrosensory feedback pathways to influence the firing properties of sensory neurons early in the processing hierarchy.

Oscillatory and burst discharge in the apteronotid electrosensory lateral line lobe

Oscillatory and burst discharge is recognized as a key element of signal processing from the level of receptor to cortical output cells in most sensory systems. The relevance of this activity for electrosensory processing has become increasingly apparent for cells in the electrosensory lateral line lobe (ELL) of gymnotiform weakly electric fish. Burst discharge by ELL pyramidal cells can be recorded in vivo and has been directly associated with feature extraction of electrosensory input. In vivo recordings have also shown that pyramidal cells are differentially tuned to the frequency of amplitude modulations across three ELL topographic maps of electroreceptor distribution. Pyramidal cell recordings in vitro reveal two forms of oscillatory discharge with properties consistent with pyramidal cell frequency tuning in vivo. One is a slow oscillation of spike discharge arising from local circuit interactions that exhibits marked changes in several properties across the sensory maps. The second is a fast, intrinsic form of burst discharge that incorporates a newly recognized interaction between somatic and dendritic membranes. These findings suggest that a differential regulation of oscillatory discharge properties across sensory maps may underlie frequency tuning in the ELL and influence feature extraction in vivo.

Interaction of GABAB-mediated inhibition with voltage-gated currents of pyramidal cells: computational mechanism of a sensory searchlight.

Interaction of GABAB-mediated inhibition with voltage-gated currents of pyramidal cells: computational mechanism of a sensory searchlight. J. Neurophysiol. 80: 3197-3213, 1998. This study examines, in the in vitro electrosensory lateral line lobe (ELL) slice preparation, mono- and disynaptic inhibition in pyramidal cells evoked by stimulation of the direct descending pathway from nucleus praeminentialis (Pd). The pathway forms the stratum fibrosum (StF) in the ELL and consists of excitatory fibers from Pd stellate cells that make monosynaptic contact with pyramidal cells and disynaptic inhibitory contacts via local interneurons and of GABAergic inhibitory fibers from Pd bipolar cells. Single or tetanic stimulation (physiological rates of 100-200 Hz) of the StF produced excitatory postsynaptic potentials (EPSPs) or compound EPSPs in ELL pyramidal cells. Slow (>600 ms) and fast inhibitory postsynaptic potentials (IPSPs; 5-50 ms) also were evoked. Application of gamma-aminobutyric acid-A (GABAA) antagonists blocked the fast inhibition and dramatically increased the firing rate response to StF tetanic stimuli. GABAA antagonists also increased the amplitude of the slow IPSP. The slow IPSP was reduced by GABAB antagonists. Blockade of excitatory amino acid (EAA) synaptic transmission allowed the monosynaptic bipolar-cell-mediated inhibition to be studied in isolation: EAA antagonists blocked most of the EPSP response to StF stimulation leaving fast and (an increased amplitude) slow IPSP components. The bipolar-cell IPSPs were mediated by GABAA and GABAB receptors as they were sensitive to GABAA and GABAB antagonists. The bipolar-cell IPSPs scaled with stimulation rate (20-400 Hz), reaching a maximum amplitude at 200 Hz. Inhibitory efficacy of bipolar-cell slow IPSPs were tested by their ability to reduce spiking in the face of sustained or brief current pulses. Established spike trains (by sustained injected current) were little affected by the onset of the slow IPSP. Weak brief currents injected during the slow IPSP were strongly inhibited. Strong brief currents could overcome the slow IPSP inhibitory effect. Inhibition was observed to interact with the intrinsic IA-like K+ currents to produce a complex control of cell spiking. Hyperpolarizing inhibition removes inactivation of IA to prevent subsequent inputs from driving the cell to threshold. Established depolarizing inputs, having allowed IA to inactivate, enable the cell to be highly sensitive to further depolarizing input. The term "conditional inhibition" is proposed to describe the general phenomenon where synaptic inhibition interacts with voltage-sensitive intrinsic currents.

Distal versus proximal inhibitory shaping of feedback excitation in the electrosensory lateral line lobe: implications for sensory filtering.

Distal versus proximal inhibitory shaping of feedback excitation in the electrosensory lateral line lobe: implications for sensory filtering. J. Neurophysiol. 80: 3214-3232, 1998. The inhibition controlling the indirect descending feedback (parallel fibers originating from cerebellar granule cells in the eminentia posterior pars granularis) to electrosensory lateral line lobe (ELL) pyramidal cells was studied using intracellular recording techniques in vitro. Parallel fibers (PF) contact stellate cells and dendrites of ventral molecular layer (VML) GABAergic interneurons. Stellate cells provide local input to pyramidal cell distal dendrites, whereas VML cells contact their somata and proximal dendrites. Single-pulse stimulation of PF evoked graded excitatory postsynaptic potentials (EPSPs) that were blocked by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl--aspartate (NMDA) antagonists. The EPSPs peaked at 6.4 +/- 1.8 ms (mean +/- SE; n = 11) but took >50 ms to decay completely. Tetanic stimulation (100 ms, 100 Hz) produced a depolarizing wave with individual EPSPs superimposed. The absolute amplitude of the individual EPSPs decreased during the train. Spike rates, established by injected current, mostly were increased, but in some cells were decreased, by tetanic stimulation. Global application of a gamma-aminobutyric acid-A (GABAA) antagonist to the recorded cell's soma and apical dendritic region increased the EPSP peak and decay phase amplitudes. Tetanic stimulation always increased current-evoked spike rates after GABAA blockade during, and for several hundred milliseconds after, the stimulus. Application of a GABAB antagonist did not have any significant effects on the PF-evoked response. This, and the lack of any long hyperpolarizing inhibitory postsynaptic potentials, suggests that VML and stellate cell inhibition does not involve GABAB receptors. Focal GABAA antagonist applications to the dorsal molecular layer (DML) and pyramidal cell layer (PCL) had contrasting effects on PF-evoked EPSPs. DML GABAA blockade significantly increased the EPSP peak amplitude but not the decay phase of the EPSP, whereas PCL GABAA-blockade significantly increased the decay phase, but not the EPSP peak, amplitude. The order of antagonist application did not affect the outcome. On the basis of the known circuitry of the ELL, we conclude that the distal inhibition originated from GABAergic molecular layer stellate cells and the proximal inhibition originated from GABAergic cells of the ventral molecular layer (VML cells). Computer modeling of distal and proximal inhibition suggests that intrinsic differences in IPSP dynamics between the distal and proximal sites may be amplified by voltage-dependent NMDA receptor and persistent sodium currents. We propose that the different time courses of stellate cell and VML cell inhibition allows them to act as low- and high-pass filters respectively on indirect descending feedback to ELL pyramidal cells.

Logarithmic time course of sensory adaptation in electrosensory afferent nerve fibers in a weakly electric fish.

1. We recorded single unit activity from individual primary electrosensory afferent axons in the posterior branch of the anterior lateral line nerve of gymnotid weakly electric fish, Apteronotus leptorhynchus. We analyzed the responses of P-type (probability-coding) afferent fibers to externally applied amplitude step changes in the quasi-sinusoidal transdermal potential established by the fish's own electric organ discharge (EOD). 2. In response to AM step increases in transdermal potential, the firing rate of P-type afferents exhibited an abrupt increase followed by an initially rapid and subsequently more gradual decay back toward the baseline level. Afferent responses continued to adapt slowly throughout the duration of prolonged step stimuli lasting > 100 s. The time course of sensory adaptation was similar for all units tested. 3. We introduce a new functional form for describing the time course of sensory adaptation in which the change in firing rate delta r decays logarithmically with time: delta r(t) = A/[B In (t) + 1]. This logarithmic form accurately describes the adaptation time course of P-type afferents over five decades in time, from milliseconds to hundreds of seconds, with only two free parameters. Using a nonlinear least-squares fitting technique, we obtained a mean value of the parameter B, which characterizes the adaptation time course, of 0.149 +/- 0.028 (mean +/- SD, n = 49). 4. We compare logarithmic fits with traditional multiexponential and power law forms and demonstrate that the logarithmic form yields a better characterization of P-type afferent responses. This analysis helps explain the variability in previously reported adaptation time constants, which have ranged from 0.2 to 3.4 s, in gymnotid P-type afferents. 5. We tested the linearity of P-type afferent responses using positive and negative AM steps of varying amplitudes. Aside from nonlinearities associated with rectification (firing rates cannot be negative) and saturation (firing rates cannot exceed the EOD frequency), we found that P-type afferent responses scaled linearly with stimulus amplitude. 6. Based on the observed linearity, we predict the frequency domain response characteristics of P-type afferents and find that the predicted gain and phase are in good agreement with experimental measurements using sinusoidal AM stimuli over a range of AM frequencies from 1 to 100 Hz. Thus the logarithmic parameterization of the step appears to accurately capture the response dynamics of P-type afferents over a wide range of behaviorally relevant AM frequencies. 7. We conclude that the temporal filtering properties of pyramidal cells in the medullary electrosensory nucleus, the electrosensory lateral line lobe (ELL), need to be reevaluated in light of the logarithmic adaptation time course in the periphery, and we discuss implications for the role of P-type afferents in driving a feedback gain control mechanism that regulated ELL pyramidal cell responsiveness.