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The Journal of Neurophysiology Vol. 79 No. 4 April 1998, pp. 1839-1857
Copyright ©1998 by the American Physiological Society
Department of Zoology, University of Oklahoma, Norman, Oklahoma 73019
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ABSTRACT |
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 Abstract
 Introduction
Methods
Results
Discussion
References
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Bastian, J. Plasticity in an electrosensory system. III. Contrasting properties of spatially segregated dendritic inputs. J. Neurophysiol. 79: 1839-1857, 1998. Efferent neurons of the first-order electrosensory processing center of the brain, the electrosensory lateral line lobe (ELL), receive electroreceptor afferent input as well as feedback inputs descending from higher centers. These ELL efferents, pyramidal cells, adaptively filter predictable patterns of sensory input while preserving sensitivity to novel stimuli. The filter mechanism involves integration of centrally generated predictive inputs with the afferent inputs being canceled. The predictive inputs, referred to as "negative image" inputs, terminate on pyramidal cell apical dendrites and generate responses that are opposite those resulting from the predictable afference, hence integration of these signals results in attenuation of pyramidal cell responses. The system also shows a robust form of plasticity; the pyramidal cells learn, with a time course of a few minutes, to cancel new patterns of repetitive inputs. This is accomplished by adjusting the strength of excitatory and inhibitory apical dendritic inputs according to an anti-Hebbian learning rule. This study focuses on the properties of two separate pathways that convey descending information to pyramidal cell apical dendrites. One pathway terminates proximally, nearer to the pyramidal cell body, whereas the other terminates distally. Recordings of ELL evoked potentials, extracellular pyramidal cell spike responses, and intracellularly recorded synaptic potentials show that the pyramidal cells respond oppositely to moderate-frequency (> ~8 Hz) single pulse stimulation or repeated (1/s) tetanic activation of these two pathways. Repetitive activation of the proximally terminating pathway results in highly facilitating responses due to potentiation of pyramidal cell excitatory postsynaptic potentials (EPSPs). These same stimuli applied to the distally terminating pathway result in a reduction of pyramidal cell responses due to depression of EPSPs and potentiation of inhibitatory postsynaptic potentials (IPSPs). Anti-Hebbian plasticity was demonstrated by pairing tetanic stimulation of either pathway with changes in the postsynaptic cell's membrane potential. After stabilization of the response potentiation due to tetanic stimulation of the proximally terminating pathway, paired postsynaptic hyperpolarization resulted in further increases in spike responses and additional potentiation of pyramidal cell EPSPs. Paired postsynaptic depolarization reduced subsequent responses to the tetanus, depressed EPSP amplitudes, and, in many cases, potentiated IPSPs. The same pattern of plasticity was observed when postsynaptic hyper- or depolarization was paired with tetanic stimulation of the distally terminating pathway except that the plasticity was superimposed on the depressed pyramidal cell responses resulting from stimulating this pathway alone. Modulation of a postsynaptic form of synaptic depression is proposed to account for the anti-Hebbian plasticity associated with both pathways.
Recent studies of several lower vertebrate acousticolateralis systems have demonstrated that adaptive filtering mechanisms exist that suppress responses to predictable patterns of sensory input without eliminating responses to novel stimuli. The rejection of predictable signals occurs in the initial processing station in the brain and the cancellation mechanism involves the integration of "negative image inputs" with the inputs from the periphery to be canceled (Bell et al. 1997a
The weakly electric fish Apteronotus leptorhynchus was used in these studies. Animals were housed in groups of 5-10 in 150 l aquaria; temperature and conductivity ranged from 25 to 27°C and 125 to 250 µS, respectively. Before surgery animals were anesthetized with tricain methanesulfonate (MS222, ~100 ppm) followed by immobilization with intramuscular injection of gallamine triethiodide (100-200 µl of 2 mg/ml solution). Fish were transferred to a 30 × 30 × 7 cm recording chamber, and the skin covering the skull was infiltrated with 2% lidocaine. After removal of the overlying skin and tissue, the rostral skull was glued to a rigid support and the ELL and cerebellum was exposed. During the course of the experiment, animals were respirated with a continuous flow of aerated water (temperature, 25-27°C; water conductivity, 100 µS).
Recording techniques
Field potential recordings were made with glass pipettes filled with 1 M NaCl (tips typically between 5 and 10 µm, electrode impedance <10 M Stimulation techniques
Electrosensory stimuli consisted of stepwise increases or decreases in the animal's EOD amplitude. Single cycles of a sinusoidal signal, having a period slightly less than that of the EOD, were synchronized to the discharge and applied as 100-ms bursts either in phase or in antiphase relative to the animal's discharge waveform to generate increases or decreases in EOD amplitude, respectively. This signal was isolated from ground via a WPI A395 linear stimulus isolation unit and applied globally to the entire fish via Ag-AgCl electrodes positioned ~15 cm from either side of the animal. Amplitude of this stimulus was set at 375 µV/cm rms. This same stimulus could be applied locally to small regions of the animal encompassing the receptive field of a given cell. In this case, the stimulus was applied between a ~1 mm silver ball electrode and a second electrode placed in the animal's mouth. The changes in EOD amplitude resulting from this stimulus were measured between a silver wire electrode, insulated except for the tip, placed on the skin surface within the receptive field of the cell studied and a second electrode implanted in the dorsal musculature. The resulting changes in EOD amplitude typically fell within the range of ±50-150 µV.
Evoked potential responses
Waveforms of evoked potentials resulting from either DML or tSF (VML) stimulation closely matched those described in studies of an in vitro preparation of the ELL of Apteronotus. Potentials were initially negative within the ELL molecular layers where activation of excitatory synapses on pyramidal cell apical dendrites creates a distributed current sink. These reversed to positive below the VML where the pyramidal cell somata and basilar dendrites provide the current source (Berman et al. 1997
Extracellular single unit responses to DML and VML stimulation
Extracellular recordings show that the responses of single ELL pyramidal cells to repeated tetanic stimulation of the DML show a progressive decay, whereas responses to the same stimulus applied to the tSF remain virtually constant. The raster diagram of Fig. 4A1 shows the responses of a nonbasilar pyramidal cell to tetanic DML stimulation; initially the cell fires in a strongly phase locked manner to the stimulus pulses but the response gradually weakens, and after ~120 s, spikes only occur on the later pulses within the train. In many cases, the initial excitatory responses to DML tetani not only decay with continuous presentation but reverse to inhibition. The histograms of Fig. 4, A2 and A4, summarize the first and last 25 1-s records, respectively, and show that the DML tetanus becomes less effective in driving this cell. The histograms of Fig. 4, A3 and A5, show the times of spike occurrence during the 10 ms after each successive stimulus within the tetanus and, as indicated by the evoked potentials, large increases in response latency occur along with the reduced responses.
Responses to DML and VML stimulation show
anti-Hebbian plasticity
Previous studies showed that pairing tetanic stimulation of the tSF with electrosensory stimuli applied to the receptive field of a given cell alters that cell's responses to subsequent tSF stimuli presented alone (Bastian 1996a
Intracellular responses to DML and tSF stimulation
Intracellular recordings were made from ELL pyramidal cells to identify the changes in postsynaptic potentials associated with the altered effectiveness of DML and VML inputs seen during tetanus and after various pairing protocols. The excitatory or inhibitory receptive field stimulation used in the experiments of Figs. 5 and 6 was replaced with hyperpolarizing or depolarizing current injection to the pyramidal cell studied. This simplifies the experiments since receptive field locations on the animal's skin no longer need to be determined and the associated mechanical disturbances are avoided. Intracellular current injection also ensures that only the cell under study is hyperpolarized or depolarized. When receptive field stimulation is used, both the recorded cell as well as a population of neurons having similarly placed receptive fields are stimulated, allowing the possibility that local circuit phenomena contribute to the plastic effects seen.
Effects of single pulse stimulation paired with postsynaptic depolarization or hyperpolarization
Single DML pulses were presented continuously at 2 Hz for 150 s to gauge the stability of intracellularly recorded EPSPs. Every other stimulus (test stimulus) was paired with weak (0.1-0.3 nA) postsynaptic hyperpolarization to block action potentials and facilitate EPSP measurement. EPSP amplitudes were measured from signal averages of successive blocks of five responses to the test stimulus and expressed as the percent of mean responses to the first 30 stimuli. Average responses of 11 pyramidal cells are shown in Fig. 8A; no significant change in EPSP amplitude was seen with continuous DML stimulation at 2 Hz. Likewise, tSF-evoked EPSPs were unchanged by similar patterns of low-frequency stimulation (data not shown).
Effects of DML and tSF tetani
Paired test stimuli were used in experiments in which tetanic stimulation of either pathway was used so that the effects on paired-pulse facilitation (PPF) could be determined. Changes in PPF often are used as an indicator of presynaptic changes in synaptic function. The twin test stimuli, 25-ms interpulse interval, were presented once per second during the 150-ms, 0.3-nA hyperpolarization used to prevent action potentials. Amplitudes of EPSPs evoked by the twin test stimuli are expressed as percent of the mean amplitude of the initial 30 responses to the first stimulus of the pair. Measurement of EPSP slopes was not attempted because in these in vivo recordings significant spontaneous synaptic activity always was present; this results in highly variable slopes. Postsynaptic potentials evoked by the DML test stimuli alone showed typical PPF averaging 170 ± 10% for 11 cells (Fig. 9A1, 0-30 s, circles). An example of EPSPs initially evoked by the paired pulses are shown in Fig. 9A2 (thin trace). After the 30 initial presentations of the test stimuli, the DML tetanus was added; its onset followed the test pulses by either 210 or 410 ms in different sets of experiments and varying this delay had no effect. The DML tetanus depressed both EPSPs evoked by test pulses (shaded region of Fig. 9A1) and examples of these recorded during the last 25 s of tetanic stimulation are shown in Fig. 9A2 (thick lines). PPF measured during the last 25 s of the tetanic stimulation fell to 144 ± 11%, and although the decrease for this data set was not statistically significant (P = 0.08, n = 11, t-test), pooling of additional data from experiments described later shows that DML tetani do cause significant reductions in PPF (see DISCUSSION). Before the tetanus, the EPSPs typically showed a steeper rise and a clear inflection, which separated the falling phase into early and late components (Fig. 9A2, arrow). The early phase of the EPSP seemed to be preferentially attenuated during the tetanus.
Effects of tetanic DML stimulation paired with postsynaptic hyper- and depolarization
The experiment described in conjunction with Fig. 9 was modified to include a phase in which the tetanic stimulation was paired with either depolarization or hyperpolarization of the postsynaptic cell to determine if plasticity in addition to that due to the tetanus itself occurred. Figure 10, A1-A5, summarizes the effects of pairing DML tetani with postsynaptic depolarization. In the first phase of these experiments ("pre tet" region of the raster of Fig. 10A1), twin test stimuli were delivered to the DML alone, at one per second, and the baseline EPSP amplitudes were measured. After this, the DML tetanus was introduced, as described in the previous section, and this continued for an additional 120 s ("tet1" region, Fig. 10A1). In the third phase of this experiment, 0.8-nA depolarizing current injection was delivered to the pyramidal cells in conjunction with the DML tetanus for 60 s ("tet + dep" region, Fig. 10A1). After this training paradigm, the DML tetanus again was delivered alone (Fig. 10A1, "tet2" region).
Effects of tetanic tSF stimulation paired with postsynaptic hyper- and depolarization
Pairing tSF tetani with postsynaptic depolarization changed responses from excitation to inhibition as was seen with DML stimulation (compare tet1 and tet2 regions of Fig. 12A1 and Fig. 13B, pre- and postspike, respectively). For the cell of Figs. 10 and 12, the change in spike response due to the paired depolarization was associated with a depression of the second test EPSP, but not the first (Fig. 12A4, compare thick and thin trace), and with a reduction in the summated depolarization seen during the tSF tetanus (Fig. 12A5, thick vs. thin trace). Figure 13A (filled symbols) shows average changes in the amplitude of the first test EPSP for 11 experiments (10 cells) of this type. As shown earlier, tetanic simulation of the tSF alone results in significant potentiation of the EPSPs evoked by the test stimuli (Fig. 13A, lightly shaded area; Fig. 13, B and C, clear and lightly shaded areas). The average effect of pairing the tSF tetanus with postsynaptic depolarization is a partial reversal of the potentiation due to the tetanus alone as shown in Fig. 13A (filled symbols and heavy shading) and Fig. 13B (black bars). Although this averaged data shows a significant decrease in the amplitude of the test EPSPs, there was some variability in the responses of individual cells. Of the 10 neurons studied, 5 showed little or no depression of the first test EPSP when averages of 25 EPSPs immediately before and after the paired stimulation were compared, however, the second test EPSP always was depressed. The remaining five cells showed larger reductions of both test EPSPs. In an earlier study of the tSF plasticity, single test stimuli were used, and no significant depression after paired tSF tetani and postsynaptic depolarization was seen (Bastian 1996a
Although the description of anti-Hebbian plasticity in the gymnotid ELL is a relatively recent event, both the anatomy of the ELL, of its efferent targets, and of its sources of feedback input are well described (Maler et al. 1981 Cancellation of reafferent and other predictable inputs
The results of earlier studies of the gymnotid ELL, and of analogous structures in other electrosensory as well as nonelectrosensory organisms, clearly demonstrate that the principal efferent neurons of these primary sensory processing nuclei cancel predictable patterns of sensory input (reviewed in Bell et al. 1997a Properties of dorsal and ventral molecular layer inputs
In studies of synaptic plasticity, the choice of the stimulation paradigm is often critically important for demonstrating the phenomenon, and even when successful stimulation techniques are used, it is frequently not known if these stimuli evoke activity similar to the natural firing patterns of the neurons involved. The nP stellate cells provide the only known excitatory input to the ELL ventral molecular layer; these cells are glutamatergic and show little or no spontaneous activity, but when stimulated with a small moving object or "electrolocation target," they generate a high-frequency burst of action potentials (Bastian and Bratton 1990 Plasticity of dorsal molecular layer inputs
Stimulation of either the DML or tSF (VML) with single pulses at frequencies below ~8 Hz evokes constant amplitude responses, but higher frequency or repeated tetanic stimulation results in progressive changes in the evoked potentials recorded in the ELL, in the spike responses of single pyramidal cells, and in the amplitudes of DML- or tSF-evoked EPSPs. The signs of these changes are opposite contingent on which pathway is studied. DML-evoked responses typically are depressed, whereas those due to high-frequency tSF stimulation rapidly potentiate and show no depression.
Plasticity of ventral molecular layer inputs
Unlike the results seen with DML stimulation, high-frequency activation of the VML inputs (tSF tetanus) results in increased pyramidal cell responses that are clearly attributable to presynaptic mechanisms. PPF was reduced significantly in the experiments of Figs. 9B1 and 13A, and when these data were pooled, PPF fell from an average initial value of 167 ± 9.6% to 110 ± 4.1% (P < 0.0001, n = 23, t-test). In vitro studies of pyramidal cell responses to similar patterns of tSF stimulation show comparable changes in field potential and pyramidal cell responses (Berman et al. 1997 Sensory searchlights and gain control
Earlier studies of the descending electrosensory inputs to the ELL dorsal and ventral molecular layers have suggested different roles for these pathways in electroreception. The nP projects directly to the ELL ventral molecular layer via the glutamatergic nP stellate cells and the GABAergic nP bipolar cells. The reciprocal topography between nP stellate neurons and ELL pyramidal cells (Maler et al. 1982
INTRODUCTION
Abstract
Introduction
Methods
Results
Discussion
References
). This phenomenon was discovered by Bell (1981, 1982). The negative image inputs supply net inhibition to their target cells when the unwanted signals are excitatory and vice versa. The negative image inputs are specific; they cancel only the predictable component of a complex sensory input leaving novel features unaltered, and they are plastic; the negative image inputs can be modified to cancel new stimulus patterns if these become predictable.
). The EOD activation of ampullary receptors, an example of a reafferent sensory input, is predictable because the animals "know" when the electric organ discharges. An EOD command related signal, generated by the circuitry that controls the electric organ, provides the negative image information to the cells implementing the cancellation (Bell and Grant 1992; Bell and von der Emde 1995; Bell et al. 1993, 1995).
; Montgomery and Bodznick 1994). Montgomery and Bodznick also have shown that cancellation of reafferent mechanosensory inputs due to gill movements occurs in teleost fish.
). As in the examples described above, the rejection of this reafferent signal results from the integration of negative image inputs with those from the periphery. Both proprioceptive inputs encoding aspects of posture as well as electrosensory inputs descending from higher centers contribute to the cancellation (Bastian 1996a).
). Sensory afferent inputs terminate on basilar or somatic dendrites of the structure's principal efferent neurons and the negative image inputs terminate on the cells' extensive apical dendrites. Integration of these signals results in strong attenuation of the input from the periphery. The plasticity underlying the adaptive characteristic of the cancellation is described as anti-Hebbian (Bell et al. 1993). That is, correlated increases in pre- and postsynaptic activity lead to reduced excitation provided by the negative image pathways and, in some cases, increases in the strength of inhibitory inputs. Presynaptic activity in conjunction with decreased afferent input leads to enhanced excitation provided by the negative image inputs. The anti-Hebbian nature of the plasticity ensures that the effects of the negative image inputs are updated to cancel optimally rather than reinforce predictable patterns of afferent input.
). Hence, basilar pyramidal cells, referred to as E cells, are excited by increased afferent activity, whereas the nonbasilar cells (I cells) are inhibited by such stimuli (Saunders and Bastian 1984). Both types of pyramidal cell send extensive apical dendrites into the ELL molecular layers. These pyramidal cells project to two higher centers, the torus semicircularis and the nucleus praeeminentialis (nP), and this latter structure is the source of descending electrosensory inputs to the ELL molecular layers (Sas and Maler 1983, 1987).
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FIG. 1.
Schematic illustration of the electrosensory lateral line lobe (ELL) of Apteronotus leptorhynchus. BP, basilar pyramidal cell; EGp, eminentia granularis posterior; nP, nucleus praeeminentialis; nVML, ventral molecular layer neuron.
). Axons terminating within the ventral molecular layer also originate in the nP, and these convey descending electrosensory information directly to the proximal regions of the pyramidal cell apical dendrites. Both excitatory (glutamatergic) and inhibitory (GABAergic) inputs have been described (Maler and Mugnaini 1994; Wang and Maler 1994), and results of earlier studies verified that the ventral molecular layer inputs are plastic and can contribute to the negative image inputs (Bastian 1996a,b).
). Comparable information about the firing characteristics of EGp granule cells, which give rise to dorsal molecular layer (DML) parallel fibers, is not available, therefore various temporal patterns of DML and VML activation were used as well as those that mimic normal VML inputs. In addition to comparing the responses of pyramidal cells to various patterns of DML and VML activation, experiments were done to determine if DML inputs are plastic and, if so, how the DML plasticity compares with the anti-Hebbian plasticity described for the VML inputs.
METHODS
Abstract
Introduction
Methods
Results
Discussion
References
), preamplified with a WPI DUO 773 electrometer and digitized at 20 kHz with Cambridge Electronic Design (CED) 1401+ data acquisition hardware and Spike2 software. Extracellular single unit recordings were made with metal filled glass microelectrodes (Frank and Becker 1964). Signals were recorded differentially via matched electrodes and amplified with a WPI DAM 70 preamplifier (300-Hz to 10-kHz filters), single spikes were isolated with a custom-built threshold detector, and spike times recorded and subsequently analyzed with the CED system. Intracellular recordings were made with alumino or borosilicate glass electrodes made with a P-87 Flaming/Brown electrode puller and filled with 3 M K-acetate. Before use electrodes were beveled (K. T. Brown BV-10 beveler, 0.05-µm alumina grinding disk) to reduce impedance to 100-150 M. Electrodes were advanced with a Burleigh piezoelectric microdrive. Judging from action potential waveforms, dendritic as well as somatic recordings were made (Turner et al. 1994), and only cells having stable resting potentials >50 mV were studied. In both extracellular and intracellular recording experiments, neurons were identified as basilar or nonbasilar pyramidal cells on the basis of stereotyped responses to stepwise changes in electric organ discharge amplitude (Saunders and Bastian 1984). Neurons were not intracellularly labeled in this study, however, based on locations of electrode penetrations, it is likely that most recordings were made from the centrolateral and centromedial subdivisions of the ELL. Intracellular records were analog tape recorded (DC-1.25 kHz bandwidth) and later A to D converted, 5-kHz sampling rate, and analyzed via the CED hardware and software.
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FIG. 2.
A1 and B1: diagrams illustrating typical dorsal molecular layer DML and tractus stratum fibrosum (tSF) stimulation sites. Brain sections correspond to levels 
8 and 1, respectively, of the A. leptorhynchus atlas (Maler et al. 1991). ALLN, anterior lateral line nerve; CCb, corpus cerebelli; cls, centrolateral segment of the ELL; cms, centromedial segment; EGa, eminentia granularis anterior; ls, lateral segment; MLF, medial longitudinal fasiculus; MOL, molecular layers; ms, medial segment; NM, nucleus medialis; PM, pacemaker nucleus; TeO, optic tectum; TS, torus semicircularis. A2: DML-evoked potential amplitudes as a function of time for different single pulse stimulation frequencies. Each point represents an average of 20 consecutive EPs. 
, 1 Hz; 
, 4 Hz; 
, 16 Hz; 
, 32 Hz. Inset: average of the 1st and last 20 responses to the 32-Hz stimulation (* and 
, respectively) B2: tSF-evoked potential amplitudes as a function of time for the same stimulation frequencies as in A2. Recording site for the waveforms shown in the inset of A2, B2 was 443 µm below the brain surface within the DML.
RESULTS
Abstract
Introduction
Methods
Results
Discussion
References
; N. J. Berman and L. Maler, unpublished observations).
and , respectively), and data from seven animals were averaged for frequencies of 16 and 32 Hz ( and , respectively). Stimulation of either pathway at frequencies <8 Hz evokes potentials of constant amplitude. Higher-frequency stimulation of the DML caused a rapidly facilitating EP which reached maximum amplitude within the first few presentations but then began a decay phase. With 32-Hz stimulation () the DML-evoked EP decays to ~50% of the steady-state amplitude seen with low-frequency stimulation. An example of the effect of continuous high-frequency DML stimulation is shown in Fig. 2A2, inset. The average of the first 20 of 500 responses to 32-Hz stimulation is indicated by (*) as is that of the last 20 responses (). The initial slope and amplitude of the latter response is significantly reduced and latency to the response peak also increased; at 32-Hz stimulation frequency, latency to peak determined from the first 20 responses averaged 6.0 ± 0.5 ms whereas that of the last 20 responses averaged 9.1 ± 0.9 ms (n = 7 animals).
) or show a delayed second phase of facilitation (32 Hz, ). Average responses to the first and last 20 presentations at 32 Hz are indicated in Fig. 2B2, inset, by * and , respectively, and the latency to the response peak increased slightly from 4.9 ± 0.56 to 6.0 ± 0.55 ms (n = 7 animals).
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FIG. 3.
A1 and A2: averages of the 1st and last 20 responses to tetanic stimulation of the DML, respectively. B1 and B2: averages of responses to the 1st and last 20 replicates of tSF stimulation. A3 and B3: average amplitudes of the 1st, 4th, and last responses evoked within each tetanus plotted over the duration of the simulation period. Each point is the average of 5 consecutive responses (pooled data from 18 animals). Recording site was within the ELL pyramidal cell layer.
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FIG. 4.
A1 and B1: raster displays of responses of a nonbasilar pyramidal cell to tetanic stimulation of the DML and tSF, respectively (100-ms train, 15-ms interpulse interval) at 1/s. A2 and A4, B2 and B4: poststimulus time histograms (PSTHs) summarizing responses to the 1st and last 25 replicates of the tetanus. A3 and A5, B3 and B5: PSTHs summarizing times of spike occurrence within the 10 ms after each stimulus of the tetanus for the 1st and last 25 replicates of the stimulus. A6 and B6: average spike frequencies ±SE computed from blocks of 5 consecutive responses and averaged for 26 pyramidal cells during tetanic stimulation of the DML and tSF, respectively. , baseline firing frequency determined from the 300-ms periods preceding the tetanus; , spike frequencies during the 100-ms tetanus.
), however, responses to the tetanus () differed contingent on the pathway stimulated. Responses to the DML tetanus decayed to near the level of spontaneous firing frequency, but the responses to tSF stimulation remained nearly constant. As suggested by the evoked potential experiments, extracellular single cell recordings show that responses to repeated tetanic stimulation of the DML decay but responses to tSF activation remain constant.
,b). This plasticity is anti-Hebbian; pairing activation of the tSF with electrosensory stimuli that excite the cell decreases the effectiveness of subsequent tSF stimuli. Often this pairing protocol reverses the net effect of tSF stimulation from excitation to inhibition. Pairing tSF stimulation with inhibitory electrosensory stimuli increases the excitatory effects of later tSF stimuli. Experiments were done using the same pairing protocols to determine if the DML inputs to pyramidal cells are also plastic. Both pathways were studied with each cell encountered.
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FIG. 5.
Responses of a basilar pyramidal cell to DML and tSF tetani before, during, and after pairing the tetanus with local electrosensory stimuli applied to the cells receptive field. Local stimulus increased or decreased electric organ discharge amplitude measured at the cell's receptive field by 117 µV. A1 and B1: effects of pairing inhibitory electrosensory stimuli with DML and tSF tetani, respectively. A2 and B2: effects of excitatory electrosensory stimuli paired with DML and tSF tetani, respectively.
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FIG. 6.
Summaries of the effects of local electrosensory stimuli applied to pyramidal receptive fields in conjunction with DML or tSF tetani. Responses were determined from blocks of 5 consecutive stimuli. Shaded regions indicate times of coincident pathway plus electrosensory stimulation ( ) or control stimulation with electrosensory stimuli alone (). A1: , DML tetanus plus inhibitory stimulation of the cells' receptive fields. Pre- and posttraining responses, determined from 25 consecutive stimulus presentations before and after the paired stimulation, averaged 4.04 ± 0.72 and 21.48 ± 1.02 spikes/s, respectively (P < 0.0001, t-test, 38 cells). , pre- and postcontrol responses (electrosensory stimulus alone): 6.05 ± 0.93 and 11.1 ± 1.1 spikes/s, respectively (P = 0.0006, t-test, 18 cells). A2: , DML tetanus plus excitatory electrosensory stimulation, pre- and posttraining responses: 5.57 ± 0.81 and 6.38 ± 0.75 spikes/s, respectively (P < 0.0001, t-test, 37 cells). , pre- and postcontrol responses: 5.34 ± 0.98 and 10.69 ± 1.04 spikes/s, respectively (P = 0.0003, t-test, 19 cells). B1: , tSF tetanus plus excitatory electrosensory stimulation, pre- and posttraining responses: 8.91 ± 0.7 and 21.6 ± 0.91 spikes/s, respectively(P < 0.0001, t-test, 38 cells). , pre- and postcontrol responses: 7.89 ± 0.93 and 8.71 ± 0.87 spikes/s, respectively (P = 0.52, t-test, 14 cells). B2: , tSF tetanus plus inhibitory electrosensory stimulation, pre- and posttraining responses: 9.72 ± 0.74 and 0.23 ± 0.67 spikes/s, respectively(P < 0.0001, t-test, 37 cells). , pre- and postcontrol responses: 5.55 ±1.03 and 5.96 ± 0.93 spikes/s, respectively (P = 0.77, t-test, 15 cells).
). The average initial response to the tetanus alone is indicated (
). Application of the inhibitory electrosensory stimulus to the cells' receptive fields (local reduction or increase in EOD amplitude for basilar and nonbasilar pyramidal cells, respectively) paired with the DML tetanus initially suppressed firing completely (shaded area) but a small recovery of responses occurred during this training period. Immediately after the training, responses to the DML tetanus were, on average, ~700% greater than the initial responses. However, these potentiated responses decayed quickly returning to baseline levels within 40 s of continued stimulation with the tetanus alone.
). The average initial responses of these cells to the tetanus is indicated (- - -). Application of the inhibitory electrosensory stimulus without the tetanus resulted in a similar suppression of responses. After the electrosensory stimulation, responses to the reapplication of the tetanus also were enhanced but significantly less so than the responses after the paired stimulation. The increased DML responses after electrosensory stimuli presented alone probably result from the pause in DML stimulation rather than the electrosensory stimulus itself. Continuous DML stimulation causes a depression of pyramidal cell responses as shown in Figs. 2-4. Removal of the tetanus during electrosensory stimulation alone allows the cell to recover from this depression, hence increased responsiveness is seen on reapplication of the DML tetanus.
. After the paired stimulation, which suppressed pyramidal cell firing, responses to the tSF tetanus also were increased significantly. The increase in tSF responses was less than that seen for the DML, 300 versus 700%, but the potentiated responses to tSF stimulation decayed significantly more slowly. Slopes of the best-fit lines to the posttraining data of Fig. 6, A1 and B1, were 0.421 and 0.223 spikes·s
1·s1,respectively, and these were significantly different as judged by a t-test of slopes (t = 4.21, P < 0.001). Control experiments (n = 14), in which the inhibitory electrosensory stimulus was presented without concomitant tSF tetani, resulted in no change in subsequent responses to tSF stimulation ().
) and 5.3 spikes/s for a subset of 19 cells subsequently presented with the excitatory electrosensory stimulus alone (). The lines indicating these initial response levels overlap. Because the DML tetanus alone caused about a 5-spikes/s increase in firing rate and responses to the electrosensory stimulus alone averaged ~80 spikes/s (, shaded region), simultaneous presentation of these stimuli should evoke increases averaging ~85 spikes/s given simple summation. Yet, when the tetanus and electrosensory stimulus were presented together, responses were only ~60 spikes/s (Fig. 6A2, , shaded area). This suggests that DML stimulation also activates an inhibitory input, however, this inhibition only becomes apparent when the pyramidal cells are driven via increased electrosensory input from the periphery. This effect is equally pronounced if a pairwise analysis is done for the subset of 19 cells stimulated with both the electrosensory stimulus alone and the electrosensory stimulus plus the DML tetanus.
). This reversal of responses from excitatory to inhibitory only occurred if the tetanus was paired with the electrosensory stimulus. After the electrosensory stimulus presented without the tetanus (), DML stimulation resulted in increased excitation, and, as suggested above, this probably represents recovery from the depression due to DML tetani.
and , shaded area). Second, after the cessation of the paired stimulation, the responses to the tSF alone also were depressed significantly, and this depression decayed with a slower time course compared with that seen in the DML experiments. The slope of the best-fit line to the average responses after the cessation of the paired tSF plus excitatory electrosensory stimuli (0.026 spikes·s1·s1) is significantly less than that fit to the responses after the paired DML stimulation (0.136 spikes·s1·s1, t = 2.22, P < 0.05).
; N. J. Berman and L. Maler, unpublished results). Additional examples of different pyramidal cells' responses to single stimuli show that the duration and relative amplitudes of the putative IPSPs are variable (Fig. 7, A3 and A4). This hyperpolarization often seemed to interrupt a longer-duration component of the EPSP, resulting in a second depolarization phase (Fig. 7A2, *). An average of four responses of the cell of Fig. 7A1 to the DML tetanus is shown in Fig. 7A5. An initial facilitation of successive EPSPs occurs followed by a relative depression of the last responses. This is similar to the changes in evoked potential amplitude seen with tetanic DML stimulation (Fig. 3, A1-A3).
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FIG. 7.
Example intracellular records from ELL pyramidal cells. A1: typical 1-s record showing the initial test stimulus occurring 50-ms after the start of a 150-ms hyperpolarization and the DML tetanus (15-ms interpulse interval) beginning 235 ms after the test stimulus. A2: average of 20 responses of this same cell to the test stimulus. A3 and A4: example postsynaptic potentials evoked by the test stimulus from 2 additional cells (averages of 20 replicates, calibration of A2 holds for A3 and A4, and B2-B4). A5: average of 4 responses of the cell of A1 to the tetanus (calibration of A5 holds for B5). B1: responses of the of the cell of A1 to tSF stimulation. B2: average of 20 responses of this same cell to the test stimulus. B3 and B4: averages of 20 responses of two additional pyramidal cells to the test stimulus. Arrows indicate the gap junction component of tSF-evoked EPSPs. B5: Average of 4 responses of the cell of A1 to the tSF tetanus.
; this very brief initial depolarization was seen in most recordings and results from a gap junction input to pyramidal cells activated by tSF stimulation. This input has been identified morphologically (Maler et al. 1981), and in vitro studies have shown it to be insensitive to blockade by low Ca2+, high Mn2+, and it persists in the presence of both N-methyl-D-aspartate (NMDA) and nonNMDA glutamate antagonists (Berman et al. 1997). The size of this initial gap junction EPSP varied among different cells, compare Fig. 7, B2 and B4, however, this component of pyramidal cell responses was not studied further. The latencies of tSF evoked EPSPs were significantly shorter than those due to DML stimulation, (4.55 ± 0.22 vs. 8.35 ± 0.35 ms, respectively, for paired latency measures to the peak of the EPSP; n = 25 pyramidal cells, P < 0.0001, t-test). Postsynaptic responses to the tSF tetanus typically consisted of a strongly facilitating EPSP, which summated and typically exceeded spike threshold (Fig. 7B5) (Bastian 1996b; Berman et al. 1997).
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FIG. 8.
Effects of postsynaptic hyper- or depolarization on responses to DML and tSF single pulse stimuli. A: average excitatory postsynaptic potential (EPSP) amplitudes evoked by continuous 2-Hz stimulation of the DML (11 cells). Each point represents the average ±SE of 5 consecutive EPSPs expressed as percent of the average of the first 30 responses. B: , average EPSP amplitudes (13 cells) before, during (shaded region), and after pairing the training stimulus with 0.8-nA postsynaptic depolarization. Training stimuli occurred 65 ms after the onset of the 100-ms change in postsynaptic membrane potential. , average EPSP amplitudes (11 cells) before, during, and after presentation of the postsynaptic depolarization alone. C: average EPSP amplitudes (9 cells) before, during (shaded area), and after pairing the training stimulus with postsynaptic hyperpolarization () or presentation of the hyperpolarization alone (). D: average tSF EPSP amplitudes (5 cells) before, during (shaded area), and after pairing the training stimulus with postsynaptic depolarization and hyperpolarization ( and , respectively). Differences in EPSP amplitudes measured over 25 s before and after postsynaptic hyper- and depolarization averaged 2.18 ± 4.94 and 1.47 ± 4.7%, respectively, (P = 0.77 and 0.68, t-tests).
. Stimulation during the first 30 s was as described for Fig. 8A. After this, each training stimulus was paired with a 100-ms, 0.8-nA depolarization, which always caused high-frequency spiking of the pyramidal cell (shaded region of Fig. 8B). EPSPs evoked by the test stimulus were depressed gradually due to the paired training stimulus plus postsynaptic depolarization. A pairwise comparison of average EPSP amplitudes determined from 25 test stimuli before and immediately after the pairing gave an average EPSP reduction of 20.7 ± 3.23% (P < 0.0001, n = 13 cells, t-test). The effects of the postsynaptic depolarization applied alone was tested for 11 of these cells (Fig. 8B, ). The training stimulus was stopped after the initial 30-s period and restarted after the 60 s during which the postsynaptic depolarization was applied alone. Analysis of each cell's responses preceding and after the depolarization alone showed an average increase in EPSP amplitude of 2.14 ± 3.21% (P = 0.52, n = 11 cells, t-test).
and , respectively; shaded area). Likewise, no differential change in EPSP amplitude was seen after the paired stimulation relative to that after the hyperpolarization alone. However, compared with the pretraining values, small increases in EPSP amplitude were seen after either treatment, averaging12.9 ± 4.5 and 13.6 ± 6.8%, respectively. The increase after the paired stimulation was significant (P = 0.02, t-test), but that after the hyperpolarization alone was not (P = 0.08, t-test).
and , respectively). Neither treatment resulted in any significant change in the amplitude of the single tSF test pulses during or after the training periods. The test stimuli used in these and subsequent experiments was routinely paired with 0.1- to 0.3-nA postsynaptic hyperpolarization to prevent the cell from producing action potentials in response to the resulting EPSP. This treatment alone did not cause any observable change in either DML-evoked EPSPs (Fig. 8A) or in the amplitude of tSF-evoked EPSPs (data not shown).
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FIG. 9.
Effects of DML and tSF tetani on pyramidal cell EPSPs. A1: EPSP amplitudes expressed as percent of initial 30 responses to the 1st test pulse before, during (shaded region), and after the addition of the DML tetanus. Circles, responses to the 1st and 2nd test stimulus, respectively. EPSP amplitudes were measured as the difference between membrane potential measured just after each stimulus artifact and at the peak of the EPSP. In some cases, the tSF-evoked EPSPs had very short latencies; in these cases, amplitude was measured as the difference between the peak and membrane potential measured just before the stimulus. Measurements were made with software which identified EPSP peaks as the largest mean of 5 consecutive voltage measurements. A2: example EPSPs evoked by the test stimuli before (thin trace) and during (thick trace) DML tetani. Records are averages of 25 replicates. Arrow, inflection point often seen separating early and late phases of DML-evoked EPSPs. B1: EPSP amplitudes before, during, and after tSF tetani. B2: EPSPs evoked by the tSF test stimuli before and during the tSF tetanus period (thin and thick lines, respectively). Calibration of A2 holds for B2.
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FIG. 10.
A1: raster display summarizing pyramidal cell spike responses to tetanic stimulation of the DML before (tet1), during (tet + dep.), and after (tet2) addition of addition of 0.8-nA depolarizing current injection. A, 2 and 3: individual records of this cell's responses to the DML twin test stimuli immediately preceding and following the paired stimulation. A4: averages of 25 responses to the test stimuli before (thin) and after (thick trace) the paired stimuli. A5: averages of 25 responses to the DML tetanus before and after the paired stimulation (thin and thick traces, respectively). Before averaging, spikes were removed from the original records. This was done with an algorithm that identified the time of occurrence and duration of the action potentials in digitized records and replaced these regions of the records with the average of membrane potential values immediately preceding and following the spikes. This technique provides a less cluttered view of slow potential changes but it also reduces the apparent amplitude of individual EPSPs within the tetanus. This procedure was not applied to any records of responses to twin test pulses. B, 1-5: responses of the same cell before, during, and after DML tetanus paired with postsynaptic hyperpolarization.
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FIG. 11.
A: changes in DML-evoked EPSP amplitudes during tetanic stimulation (circles and light shading), during tetani paired with postsynaptic depolarization (filed symbols, heavy shading, 12 replicates, 11 cells), and during tetani paired with postsynaptic hyperpolarization (open symbols, heavy shading, 13 replicates, 11 cells). For each cell, EPSP amplitudes were measured from means of successive blocks of 5 responses. Each point represents the average ± SE of responses expressed as percent of the mean response to the first 30 replicates of the test stimulus given alone. B: histograms summarizing average EPSP amplitudes evoked by the first (EPSP1) and second (EPSP2) test stimuli determined from 25 stimulation trials before the tetanus (open bars) and immediately before and after the paired tetanus plus postsynaptic depolarization (grey and black bars, respectively). Reductions in EPSP amplitudes due to the tetanus alone averaged 1.3 ± 0.26 and 2.4 ± 0.4 mV for the 1st and 2nd test EPSPs, respectively. Both reductions are significant (P 
0.0004, t-tests). Reductions in EPSP amplitudes due to addition of the postsynaptic depolarization averaged 0.73 ± 0.24 and 0.81 ± 0.22 mV, respectively, and these additional reductions also are significant (P = 0.009 and 0.003, t-tests). Hatched bars show average spike responses to the DML tetanus before (pre, open bars) and after (post, black bars) the paired stimulation. C: average EPSP amplitudes evoked by the 1st and 2nd test stimuli before the onset of the tetanus, before the tetanus plus hyperpolarization and after this treatment (open, hatched, and black bars, respectively). Reductions in the 1st and 2nd test EPSP amplitudes due to the tetanus averaged 1.7 ± 0.49 and 2.5 ± 0.32 mV, respectively (P = 0.005 and <0.0001, t-tests). After DML stimulation paired with postsynaptic hyperpolarization, EPSPs increased by 0.54 ± 0.12 and 0.43 ± 0.11 mV, respectively (P = 0.0007 and <0.0001). Hatched bars show average spikes responses before and after the paired stimulation.
). Further studies are needed to determine whether differences in tSF stimulation sites, individual variation among pyramidal cells, or some other unknown factor accounts for this variability.
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FIG. 12.
Summary of responses of the pyramidal cell of Fig. 10 to tSF stimulation paired with postsynaptic depolarization (A1-A5) and paired with postsynaptic hyperpolarization (B1-B5). Descriptions of Fig. 10 apply to these data; spikes were removed from the records averaged in A5 and B5.
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FIG. 13.
A: changes in tSF-evoked EPSP amplitudes during tetanic stimulation (circles and light shading), during tetani paired with postsynaptic depolarization (filled symbols, heavy shading, 12 replicates, 11 cells), and during tetani paired with postsynaptic hyperpolarization (open symbols, heavy shading, 16 replicates, 12 cells). B: average amplitudes of test EPSPs (EPSP1 and EPSP2) before the tetanus (open bars), during the tetanus but before postsynaptic depolarization (grey bars), and during tetanus but after the postsynaptic depolarization (black bars). Increases in EPSP amplitudes due to the tetanus averaged 1.7 ± 0.2 and 0.9 ± 0.31 mV for EPSP1 and -2, respectively (P = 0.0001 and 0.013, t-test). Reductions due to the paired depolarization averaged 0.61 ± 0.16 and 0.69 ± 0.14 mV (P = 0.003 and 0.0007, t-test). Before the tetanus PPF averaged 143 ± 13.7%, It was reduced to 114 ± 5.5% during the tetanus (P = 0.043 t-test) and after the paired depolarization PPF averaged 113 ± 6.4%. The addition of the postsynaptic depolarization had no significant effect on PPF (P = 0.99,t-test). Hatched bars show changes in spike responses before (pre) and after (post) the paired stimulation. C: average EPSP amplitudes before tetanus and before and after the tetanus paired with postsynaptic hyperpolarization (open, grey, and black bars, respectively). Increases in the 1st and 2nd test EPSP amplitudes averaged 1.33 ± 0.19 and 0.41 ± 0.15 mv, respectively (P < 0.0001 and = 0.017, t-test). Increases in EPSP amplitudes after paired tSF tetanus plus postsynaptic hyperpolarization averaged 0.41 ± 0.09 and 0.33 ± 0.07 (P = 0.0002 and <0.0001, t-test). Before the tetanus, PPF averaged 182 ± 12.1%. It was reduced to 99.9 ± 4.9% during the tetanus (P < 0.0001, t-test), and after the paired hyperpolarization, PPF averaged 98.5 ± 4.9% (P = 0.72, t-test). Hatched bars show average changes in spike response before and after the paired stimulation.
DISCUSSION
Abstract
Introduction
Methods
Results
Discussion
References
, 1982; Sas and Maler 1983, 1987). Additionally, the physiological responses of the principal ELL cell types to relatively "natural' stimuli have been studied in in vivo preparations, as have n. praeeminentialis neurons providing electrosensory feedback to the ELL molecular layers (Bastian 1981, 1986a,b; Bastian and Bratton 1990; Bratton and Bastian 1990; Saunders and Bastian 1984; Shumway 1989). In vitro studies of the ELL have contributed greatly to the understanding of the synaptic physiology and membrane specializations of the ELL pyramidal cells (Berman et al. 1997; Mathieson and Maler 1988; Turner et al. 1994; Wang and Maler 1997). Both in vivo and in vitro pharmacological experiments as well as anatomic (immunohistochemical) studies have identified the neurotransmitters used by the major afferent and efferent cell types (Bastian 1993; Maler and Mugnaini 1994; Nadi and Maler 1987; Shumway and Maler 1989; Wang and Maler 1994) and, most recently, descriptions of the distribution of important intracellular receptors and signaling molecules have appeared (Berman et al. 1995; Maler and Wang 1997). This detailed background information plus a good understanding the roles of the electrosensory system in these animals' lives (see Bullock and Heiligenberg 1986, for reviews) should facilitate efforts to understand the significance of such robust plasticity at the first stage in the sensory processing hierarchy.
). It has been demonstrated in gymnotids that changes in posture alter the amplitude of the discharge sensed by the electroreceptors, and many ELL pyramidal cells show virtually no response to this type of stimulus despite the fact that electroreceptors are strongly driven (Bastian 1995). Furthermore, by altering the pattern of electrosensory stimulation associated with postural changes, one can demonstrate that the mechanism underlying the rejection of these reafferent stimuli is plastic. The system can learn, with a time course of minutes, to cancel new patterns of stimulation.
) and the cellular mechanisms by which the cancellation is achieved also seem similar. Predictive inputs, which may include corollary discharge information, proprioceptive information, or descending sensory information of the same modality as that of the signals being canceled, are received via the apical dendrites of the neurons performing the cancellation. Because the predictive inputs provide "negative images" of the afferent input to be canceled, integration of these signals results in little or no change in the cells' output. The site of the plasticity seems to be at the apical dendritic synapses receiving the predictive information and the form of plasticity is best described as anti-Hebbian (Bell et al. 1993). Hence, when activity in the negative image or predictive pathway repeatedly occurs simultaneously with increased activity or depolarization of the postsynaptic cell, the net excitatory drive provided by the predictive pathway is reduced and often reverses to net inhibition. Conversely, when the predictive inputs repetitively coincide with reductions in postsynaptic activity or hyperpolarization, the net excitation that they provide isincreased.
). Because the DML, but not the tSF, is known to convey proprioceptive information, the DML inputs also are expected to show anti-Hebbian plasticity. The results of this study confirm that both the DML and tSF inputs display similar patterns of synaptic plasticity when they are activated synchronously with postsynaptic changes in membranepotential.
; Sas and Maler 1983). Hence, tetanic stimuli that mimic the stellate cell's normal responses were used to activate the VML inputs to pyramidal cells. The other major category of nP efferents projecting to the VML, the bipolar cells, areGABAergic but their firing pattern is unknown.
). The activity patterns of two categories of EGp afferents that provide input to the granule cells have been described. Both the nP multipolar cells, which convey descending electrosensory information to the EGp, and fibers conveying proprioceptive information to the EGp are spontaneously active at high rates averaging, 72 and 78 Hz, respectively, and both respond to natural forms of stimulation with slowly adapting or nonadapting responses that can exceed 100 spikes/s (Bastian 1995; Bratton and Bastian 1990). The high firing frequencies of these inputs to the EGp are similar to those described for mossy fiber inputs to cerebellar granule cells (Van Kan et al. 1993). The available evidence suggests that the EGp granule cells are likely to be capable of firing at high frequencies and the tetanic stimulus used probably doesn't exceed their normal dynamic range.
; Dunwiddie and Hass 1985; Simmons et al. 1994). Depletion of releaseable vesicle pools also could account for the EPSP depression seen with DML stimulation; however, such depletion is expected to result in paired-pulse depression not facilitation (Debanne et al. 1996; Thies 1965). 3) The EPSP depression resulting from DML tetani could result, at least in part, from the potentiation of DML-evoked IPSPs. Potentiation of GABAergic responses has been described in cerebellar Purkinje cells after paired presynaptic activity and postsynaptic depolarization (Kano 1996), and, if present in ELL pyramidal cells, this could contribute to the depression of EPSPs as well as account for the reversal of the effects of DML parallel fiber activity from net excitation to inhibition. Recent in vitro studies of the ELL showed that tetanus-induced depression of DML-evoked EPSPs could be reversed partially by application of 
-aminobutyric acid (GABA) antagonists (N. J. Berman and L. Maler, unpublished data).
; Ito et al. 1982; Lev-Ram et al. 1997). However, it can occur in response to strong activation of parallel fibers alone (Hartell 1996). An LTD-like mechanism recently was described in mormyrid weakly electric fish (Bell et al. 1997b), and this or a similar phenomenon also could account for the DML-evoked EPSP depression seen in response to the tetanus alone. Such a depression of DML-evoked EPSPs is expected to unmask DML-evoked IPSPs, resulting in the conversion of the net effect of DML stimulation from excitation to inhibition (e.g., Fig. 10, A1 and A5). Furthermore, modulation of postsynaptic depression resulting from the manipulation of the postsynaptic cell's membrane potential could account for the anti-Hebbian plasticity that has been observed.
) or in a cerebellar granule cell-Purkinje cell culture (Hirano 1990) results in EPSP potentiation, and the in vitro studies of the ELL (Maler and Wang 1997; D. Wang and L. Maler, unpublished results) also clearly demonstrate that PTP occurs with stimulation of the DML parallel fibers. However, the expression of this potentiation may be outweighed by the proposed postsynaptic depression that develops simultaneously. The changes in EPSP amplitudes seen therefore may result from a more complex mix of pre- and postsynaptic effects.
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FIG. 14.
Diagrammatic illustration of hypothesized pre- and postsynaptic contributions to the patterns of DML (A, 1 and 2) and VML (B, 1 and 2) plasticity seen. See text for details.
; Plant 1994), and an analysis of the time course of the changes indicates a PTP-like phenomenon (Wang and Maler 1997). Furthermore, in vitro studies of this potentiation showed that bath application of the CAMKII antagonist1 - (N , O - b i s -[5- i s o q u i n o l i n e s u l f o n y l]-N- m e t h y l-L-t y r osyl)-4-phenyl-piperazine (KN-62) blocked both PPF and PTP. Postsynaptic application of KN-62 via intracellular injection, however, did not alter PTP indicating a presynaptic locus (Wang 1997; D. Wang and L. Maler, unpublished results). Thus the potentiation of pyramidal cell responses to tSF high frequency or tetanic stimulation alone probably results from large presynaptic changes in transmitter release.
). Additionally, in vitro results of N. J. Berman and L. Maler (unpublished results) show the presence of brief bicuculline-sensitive IPSPs that also could contribute to the EPSP depression. Additional studies are needed to assess the relative contributions of the postsynaptic depression proposed here and of brief synchronously generated IPSPs in the modulation of both DML and tSF-evoked EPSP amplitudes.
).
30 min if stimulation of the system is interrupted after training (Bastian 1996a; Bell 1986; Bell et al. 1997a).
), the stellate cell's very strong responses to small moving electrolocation targets, and the fact that they provide a powerful excitatory input to pyramidal cells led to the suggestion that the stellate neurons provide positive feedback to pyramidal cells (Bratton and Bastian 1990; Maler and Mugnaini 1993). Their proposed role was to act as a sensory searchlight, as described by Crick (1984), accentuating the responses to relevant stimuli, and the results of this and of earlier studies in which the tSF is directly stimulated verifies that the nP stellate cells can provide excitatory, positive feedback input to the pyramidal cells (Bastian 1996b; Berman et al. 1997; Wang 1997). However, the VML inputs to pyramidal cells are plastic; reafferent as well as other repetitive patterns of electrosensory input are attenuated gradually if the stimulus is maintained. This attenuation of predictable inputs indicates that the proposed searchlight effects are transitory. Within ~2 min of continuous stimulation, this descending pathway does not simply cease providing positive feedback; instead a process of active cancellation develops. The neural representation of novel stimuli will be augmented initially by net positive feedback excitation from stellate to pyramidal cells, but if the stimuli persist, the synaptic strengths of descending excitatory and inhibitory inputs are adjusted to cancel the persistent afferent input. The searchlight effect can be thought of as adapting to persistent stimuli.
), and the relatively poor responses of the projection cells (nP multipolar cells) to moving electrolocation targets suggested a different role for this pathway. Pyramidal cell responses to electrolocation targets were found to be relatively insensitive to changes in the amplitude of the animal's electric organ discharge, suggesting that a gain control mechanism also may operate at the level of the ELL. Destruction of the EGp via lesions or anesthetic blockade of the electrosensory input from the nP to the EGp disrupted gain control implicating the DML parallel fibers in this function (Bastian 1986a-c). The gain control was suggested to result from the modulation of pyramidal cell inhibition provided by ELL interneurons, which are driven by DML parallel fibers, and Shumway and Maler (1989) showed that GABA antagonists also disrupted this function. Although the nP multipolar cells respond poorly to moving targets, they accurately encode the animal's electric organ discharge amplitude. They receive input from a very slowly or nonadapting population of ELL output neurons (Bastian and Courtright 1991) and also respond to long-term changes in EOD amplitude with little or no adaptation. Hence, the nP multipolar cells can provide a suitable "error signal" to adjust pyramidal cell gain as electric organ discharge amplitude changes.
). Whether the aberrant responses result from a persistent stimulus in the environment or some alteration in the physiology of groups of electroreceptors should not matter. The anti-Hebbian plasticity will ensure that the responsiveness of subsets of pyramidal cells does not vary excessively.
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ACKNOWLEDGEMENTS |
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I am grateful to Drs. C Bell and L. Maler for helpful discussions of this work.
This work was supported by National Institute of Neurological Disorders and Stroke Grant NS-12337.
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FOOTNOTES |
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Address for reprint requests: J. Bastian, Dept. of Zoology, University of Oklahoma, 730 Van Vleet Oval, Normal, OK 73019.
Received 2 October 1997; accepted in final form 3 December 1997.
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REFERENCES |
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Abstract
Introduction
Methods
Results
Discussion
References
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