Modeling cancelation of periodic inputs with burst-STDP and feedback.

Prediction and cancelation of redundant information is an important feature that many neural systems must display in order to efficiently code external signals. We develop an analytic framework for such cancelation in sensory neurons produced by a cerebellar-like structure in wave-type electric fish. Our biologically plausible mechanism is motivated by experimental evidence of cancelation of periodic input arising from the proximity of conspecifics as well as tail motion. This mechanism involves elements present in a wide range of systems: (1) stimulus-driven feedback to the neurons acting as detectors, (2) a large variety of temporal delays in the pathways transmitting such feedback, responsible for producing frequency channels, and (3) burst-induced long-term plasticity. The bursting arises from back-propagating action potentials. Bursting events drive the input frequency-dependent learning rule, which in turn affects the feedback input and thus the burst rate. We show how the mean firing rate and the rate of production of 2- and 4-spike bursts (the main learning events) can be estimated analytically for a leaky integrate-and-fire model driven by (slow) sinusoidal, back-propagating and feedback inputs as well as rectified filtered noise. The effect of bursts on the average synaptic strength is also derived. Our results shed light on why bursts rather than single spikes can drive learning in such networks "online", i.e. in the absence of a correlative discharge. Phase locked spiking in frequency specific channels together with a frequency-dependent STDP window size regulate burst probability and duration self-consistently to implement cancelation.

Envelope gating and noise shaping in populations of noisy neurons.

Narrowband signals have fast and slow time scales. The transmission of narrowband signal features on both times cales, by spiking neurons, is demonstrated experimentally and theoretically. The interaction of the narrowband input and the threshold nonlinearity may create out-of-band interference, hindering the transmission of signals in a low-frequency range. The resultant out-of-band signal is the "envelope," or time-varying modulation of the narrowband signal. The levels of noise and nonlinearity intrinsic to the neuron gate transmission on the slow "envelope" time scale. When a narrowband and a distinct slow signal drive the neuron, the slow signal may be poorly transmitted. Increasing intrinsic noise in an averaging network removes the envelope in favor of the slow signal, paradoxically increasing the signal-to-noise ratio. These gating effects are generic for threshold and excitable systems.

Blurring of the senses: common cues for distance perception in diverse sensory systems.

Distance perception is an essential task of sensory systems. Our visual systems effectively use binocular visual cues to determine an object's distance. Other visual, but monocular, cues are also available for distance perception. Visual contrast and image blur are two such cues [O'Shea et al., 1994. Vis. Res. 34, 1595-1604; O'Shea et al., 1997. Perception 26, 599-612; Mather, 1997. Perception 26, 1147-1158]. We show the effects of combining these cues using a simple psychophysical test. The novelty in our approach is that our exact choice of visual stimuli allows us to show a direct parallel between visual distance perception and distance perception using an entirely different sense, the electric sense of weakly electric fish. We discuss previous work on electrosensory psychophysics [von der Emde et al., 1998. Nature 395, 890-894] and show that cues used for electrosensory distance perception are analogous to visual contrast and blur. We also suggest that analogous cues are involved in auditory distance perception. The utilization of analogous cues implies that these diverse sensory systems perform similar computations for distance perception.

Model of gamma frequency burst discharge generated by conditional backpropagation.

Pyramidal cells of the electrosensory lateral line lobe (ELL) of the weakly electric fish Apteronotus leptorhynchus have been shown to produce oscillatory burst discharge in the gamma-frequency range (20-80 Hz) in response to constant depolarizing stimuli. Previous in vitro studies have shown that these bursts arise through a recurring spike backpropagation from soma to apical dendrites that is conditional on the frequency of action potential discharge ("conditional backpropagation"). Spike bursts are characterized by a progressive decrease in inter-spike intervals (ISIs), and an increase of dendritic spike duration and the amplitude of a somatic depolarizing afterpotential (DAP). The bursts are terminated when a high-frequency somatic spike doublet exceeds the dendritic spike refractory period, preventing spike backpropagation. We present a detailed multi-compartmental model of an ELL basilar pyramidal cell to simulate somatic and dendritic spike discharge and test the conditions necessary to produce a burst output. The model ionic channels are described by modified Hodgkin-Huxley equations and distributed over both soma and dendrites under the constraint of available immunocytochemical and electrophysiological data. The currents modeled are somatic and dendritic sodium and potassium involved in action potential generation, somatic and proximal apical dendritic persistent sodium, and K(V)3.3 and fast transient A-like potassium channels distributed over the entire model cell. The core model produces realistic somatic and dendritic spikes, differential spike refractory periods, and a somatic DAP. However, the core model does not produce oscillatory spike bursts with constant depolarizing stimuli. We find that a cumulative inactivation of potassium channels underlying dendritic spike repolarization is a necessary condition for the model to produce a sustained gamma-frequency burst pattern matching experimental results. This cumulative inactivation accounts for a frequency-dependent broadening of dendritic spikes and results in a conditional failure of backpropagation when the intraburst ISI exceeds dendritic spike refractory period, terminating the burst. These findings implicate ion channels involved in repolarizing dendritic spikes as being central to the process of conditional backpropagation and oscillatory burst discharge in this principal sensory output neuron of the ELL.

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.

Negative interspike interval correlations increase the neuronal capacity for encoding time-dependent stimuli.

Accurate detection of sensory input is essential for the survival of a species. Weakly electric fish use amplitude modulations of their self-generated electric field to probe their environment. P-type electroreceptors convert these modulations into trains of action potentials. Cumulative relative refractoriness in these afferents leads to negatively correlated successive interspike intervals (ISIs). We use simple and accurate models of P-unit firing to show that these refractory effects lead to a substantial increase in the animal's ability to detect sensory stimuli. This assessment is based on two approaches, signal detection theory and information theory. The former is appropriate for low-frequency stimuli, and the latter for high-frequency stimuli. For low frequencies, we find that signal detection is dependent on differences in mean firing rate and is optimal for a counting time at which spike train variability is minimal. Furthermore, we demonstrate that this minimum arises from the presence of negative ISI correlations at short lags and of positive ISI correlations that extend out to long lags. Although ISI correlations might be expected to reduce information transfer, in fact we find that they improve information transmission about time-varying stimuli. This is attributable to the differential effect that these correlations have on the noise and baseline entropies. Furthermore, the gain in information transmission rate attributable to correlations exhibits a resonance as a function of stimulus bandwidth; the maximum occurs when the inverse of the cutoff frequency of the stimulus is of the order of the decay time constant of refractory effects. Finally, we show that the loss of potential information caused by a decrease in spike-timing resolution is smaller for low stimulus cutoff frequencies than for high ones. This suggests that a rate code is used for the encoding of low-frequency stimuli, whereas spike timing is important for the encoding of high-frequency stimuli.

Neuronal population codes and the perception of object distance in weakly electric fish.

Weakly electric fish use an electric sense to navigate and capture prey in the dark. Objects in the surroundings of the fish produce distortions in their self-generated electric field; these distortions form a two-dimensional Gaussian-like electric image on the skin surface. To determine the distance of an object, the peak amplitude and width of its electric image must be estimated. These sensory features are encoded by a neuronal population in the early stages of the electrosensory pathway, but are not represented with classic bell-shaped neuronal tuning curves. In contrast, bell-shaped tuning curves do characterize the neuronal responses to the location of the electric image on the body surface, such that parallel two-dimensional maps of this feature are formed. In the case of such two-dimensional maps, theoretical results suggest that the width of neural tuning should have no effect on the accuracy of a population code. Here we show that although the spatial scale of the electrosensory maps does not affect the accuracy of encoding the body surface location of the electric image, maps with narrower tuning are better for estimating image width and those with wider tuning are better for estimating image amplitude. We quantitatively evaluate a two-step algorithm for distance perception involving the sequential estimation of peak amplitude and width of the electric image. This algorithm is best implemented by two neural maps with different tuning widths. These results suggest that multiple maps of sensory features may be specialized with different tuning widths, for encoding additional sensory features that are not explicitly mapped.

Subtractive and divisive inhibition: effect of voltage-dependent inhibitory conductances and noise.

The influence of voltage-dependent inhibitory conductances on firing rate versus input current (f-I) curves is studied using simulations from a new compartmental model of a pyramidal cell of the weakly electric fish Apteronotus leptorhynchus. The voltage dependence of shunting-type inhibition enhances the subtractive effect of inhibition on f-I curves previously demonstrated in Holt and Koch (1997) for the voltage-independent case. This increased effectiveness is explained using the behavior of the average subthreshold voltage with input current and, in particular, the nonlinearity of Ohm's law in the subthreshold regime. Our simulations also reveal, for both voltage-dependent and -independent inhibitory conductances, a divisive inhibition regime at low frequencies (f < 40 Hz). This regime, dependent on stochastic inhibitory synaptic input and a coupling of inhibitory strength and variance, gives way to subtractive inhibition at higher-output frequencies (f > 40 Hz). A simple leaky integrate-and-fire type model that incorporates the voltage dependence supports the results from our full ionic simulations.

Differential expression of the PSD-95 gene family in electrosensory neurons.

The PSD-95 family of membrane-associated guanylate kinase (MAGUK) proteins are involved in the assembly and organization of neurotransmitter receptors at excitatory synapses in the vertebrate nervous system. We have isolated partial cDNAs for five PSD-95 family members from Apteronotus leptorhynchus brain RNA using a degenerate PCR method. The amino acid sequences deduced indicate that A. leptorhynchus neurons express homologues of the mammalian PSD-93, SAP-97, and SAP-102 MAGUKs and two homologues of mammalian PSD-95. In situ hybridization experiments have been carried out to localize the cellular expression of all five MAGUK mRNAs in the central nervous system of A. leptorhynchus. In the cerebellum the expression patterns are highly similar to patterns reported for mammalian cerebellum, suggesting an evolutionary conservation of the functional roles in this gene family. Cellular levels of expression of the PSD-95 MAGUK mRNAs and the NMDAR-1 mRNA were highly correlated in neurons of the dorsal forebrain but were not correlated in neurons of the electrosensory lateral line lobe (ELL) or the cerebellum. These results suggest that the expression of PSD-95 MAGUK genes in forebrain neurons may provide mechanisms for synaptic organization that are not shared by neurons in the ELL and cerebellum.

Suprathreshold stochastic firing dynamics with memory in P-type electroreceptors.

Weakly electric fish generate a periodic electric field as a carrier signal for active location and communication tasks. Highly sensitive P-type receptors on their surface fire in response to carrier amplitude modulations (AM's) in a noisy phase locked fashion. A simple generic model of receptor activity and signal encoding is presented. Its suprathreshold dynamics, memory and receptor noise reproduce observed firing interval distributions and correlations. The model ultimately explains how smooth responses to AM's are compatible with its nonlinear phase locking properties, and reveals how receptor noise can sometimes enhance the encoding of small yet suprathreshold AM's.

Site-site communication in the EF-hand Ca2+-binding protein calbindin D9k.

The cooperative binding of Ca2+ ions is an essential functional property of the EF-hand family of Ca2+-binding proteins. To understand how these proteins function, it is essential to characterize intermediate binding states in addition to the apo- and holo-proteins. The three-dimensional solution structure and fast time scale internal motional dynamics of the backbone have been determined for the half-saturated state of the N56A mutant of calbindin D9k with Ca2+ bound only in the N-terminal site. The extent of conformational reorganization and a loss of flexibility in the C-terminal EF-hand upon binding of an ion in the N-terminal EF-hand provide clear evidence of the importance of site-site interactions in this family of proteins, and demonstrates the strength of long-range effects in the cooperative EF-hand Ca2+-binding domain.

Distribution of protein kinase C in the brain of Apteronotus leptorhynchus as revealed by phorbol ester binding.

An antibody to the mammalian protein kinase C alpha (PKCalpha) subunit and brain dissection was used for immunoblot analysis of this protein in various brain regions of Apteronotus leptorhynchus. Western blots revealed that the antibody labeled a band of the expected molecular mass (approximately 80 kDa) for this enzyme in mammalian cortex and electric fish brain, suggesting that this protein is also found in gymnotiform brain. The 80-kDa band was enriched in fish forebrain and cerebellum compared with hypothalamus and brainstem areas. [3H]Phorbol 12,13-dibutyrate ([3H]PDBu) binding was used as a marker for the distribution of protein kinase C (PKC). [3H]PDBu binding was nearly completely displaced by excess cold PDBu; specific [3H]PDBu binding sites were heterogenously distributed with high densities in some gray matter regions and negligible densities in fiber tracts. A very high density of [3H]PDBu binding sites were found in the dorsal forebrain with far lower densities in most ventral forebrain nuclei. Low binding densities were observed in preoptic and hypothalamic areas with the exception of the nucleus diffusus and nucleus tuberis anterior. The thalamus and midbrain also had only low levels of binding. The cerebellar molecular layer had dense binding, in contrast to the granule cell layer where binding was negligible. In the electrosensory lateral line lobe (ELL), there was moderate binding in the dorsal molecular layer, which contains cerebellar parallel fibers; the other layers of the ELL had far lower binding densities.

Distribution of adenylate cyclase in the brain of Apteronotus leptorhynchus as revealed by forskolin binding.

An antibody directed against an isoform of the rat regulatory subunit of protein kinase A and brain dissection was used for immunoblot analysis of this protein in various brain regions of Apteronotus leptorhynchus. Western blots revealed that the antibody labeled a band of the expected molecular mass (approximately 53 kDa) for this enzyme in mammalian cortex and electric fish brain, suggesting that this protein is also found in fish brains. The 53-kDa band was enriched in fish forebrain. [3H]Forskolin binding was used as a marker for the distribution of adenylate cyclase. [3H]Forskolin binding was nearly completely displaced by excess cold forskolin; specific [3H]forskolin binding sites were heterogenously distributed with relatively high densities in some gray matter regions and low densities in fiber tracts. A high density of [3H]forskolin binding sites was found in the dorsal forebrain with lower densities in most ventral forebrain nuclei. Moderate binding densities were observed in the preoptic and hypothalamic areas with the exception of the nucleus tuberis anterior, which had high levels. The thalamus and midbrain had low levels of binding. The cerebellar molecular layer had dense binding, in contrast to the granule cell layer where binding was low. In the electrosensory lateral line lobe (ELL), there was moderate binding in the dorsal and ventral molecular layers, which contain feedback inputs; the cellular layers of the ELL had low binding densities.

Distribution of calcium/calmodulin-dependent kinase 2 in the brain of Apteronotus leptorhynchus.

Antibodies directed against the mammalian alpha and beta subunits of calcium/calmodulin-dependent kinase 2 (CaMK2) and brain dissection were used for immunoblot analysis of these proteins in various brain regions of Apteronotus leptorhynchus. Western blots revealed that the CaMK2alpha antibody labeled a single band of the expected molecular mass (approximately 50 kDa) for this enzyme in rat cortex and electric fish brain. CaMK2alpha was enriched in fish forebrain and hypothalamus and also strongly expressed in midbrain sensory areas. Western blots revealed that CaMK2beta antibodies labeled bands in an appropriate molecular mass range (approximately 58-64 kDa) for this enzyme in mammalian cortex and electric fish brain. However, a higher molecular mass band (approximately 80 kDa) was also labeled; because all these bands were eliminated by preadsorbtion with the CaMK2-derived peptide antigen, they may all represent CaMK2beta-like isoforms. We mapped the brain distribution of CaMK2 isoforms with emphasis on the electrosensory system. CaMK2alpha was present at high density in dorsal forebrain, hypothalamic nuclei, torus semicircularis, and tectum. It was also enriched in discrete fiber tracts in forebrain, diencephalon, and rhombencephalon. CaMK2beta-like isoforms were enriched in ventral forebrain, hypothalamic nuclei, torus semicircularis and the reticular formation. Unlike CaMK2alpha, CaMK2beta -like isoforms were predominantly present in cell bodies and rarely found in fiber tracts or neuropil. In the electrosensory lateral line lobe, CaMK2alpha was restricted to specific feedback fibers, i.e., tractus stratum fibrosum and its terminal field in the ventral molecular layer. In contrast, CaMK2beta-like isoforms were enriched in somata and dendrites of pyramidal cells and granular interneurons.

Neural architecture of the electrosensory lateral line lobe: adaptations for coincidence detection, a sensory searchlight and frequency-dependent adaptive filtering

The electrosensory lateral line lobe (ELL) of weakly electric fish is the only nucleus that receives direct input from peripheral electroreceptor afferents. This review summarises the neurotransmitters, receptors and second messengers identified in the intrinsic circuitry of the ELL and the extrinsic descending direct and indirect feedback pathways, as revealed by recent in vitro and in vivo studies. Several hypotheses of circuitry function are examined on this basis and on the basis of recent functional evidence: (1) fast primary afferent excitatory postsynaptic potentials (EPSPs) and fast granule cell 2 GABAA inhibitory postsynaptic potentials (IPSPs) suggest the involvement of basilar pyramidal cells in coincidence detection; (2) voltage-dependent EPSPs and IPSPs, dendritic spike bursts and frequency-dependent synaptic facilitation support a sensory searchlight role for the direct feedback pathway; and (3) the contributions of distal and proximal inhibition, anti-Hebbian plasticity and beam versus isolated fiber activity patterns are discussed with reference to an adaptive spatio-temporal filtering role for the indirect descending pathway.

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.

Molecular biology of the apteronotus NMDA receptor NR1 subunit.

The complete sequences and expression patterns of the NR1 (aptNR1) subunit of the N-methyl-d-aspartate (NMDA) receptor and its alternative splice isoforms have been determined for the weakly electric fish Apteronotus leptorhynchus. The deduced amino acid sequence of aptNR1 is approximately 88 % identical to the NR1 sequences of other vertebrate. Two of the three alternative splice cassettes previously described for mammalian NR1s, N1 and C1, are present in aptNR1, but the third cassette, C2, is not found. In addition, two teleost-specific splice cassettes occur on the N-terminal side of the C1 sequence. The cellular patterns of aptNR1 expression, including the patterns of N1 and C1 splicing, have been mapped using the in situ hybridization technique. High levels of aptNR1 mRNA were detected throughout the central nervous system including most neurons of the electrosensory system, with the highest levels in electrosensory lateral line lobe pyramidal cells. Expression of the N1 splice isoform was higher in more caudal regions of the brain, and expression of the C1 splice isoform was higher in more rostral regions. The N1 splice isoform was present in almost all NR1-positive cells, in contrast to the C1 splice isoform which was restricted to a subset of NR1-positive cells. These results demonstrate that the NR1 subunit of the NMDA receptor is evolutionarily conserved across species and that regulation of alternative RNA splicing modulates the properties of NR1 in different neurons of the central nervous system of A. leptorhynchus.

High resolution solution structure of apo calcyclin and structural variations in the S100 family of calcium-binding proteins.

The three-dimensional solution structure of apo rabbit lung calcyclin has been refined to high resolution through the use of heteronuclear NMR spectroscopy and 13C, 15N-enriched protein. Upon completing the assignment of virtually all of the 15N, 13C and 1H NMR resonances, the solution structure was determined from a combination of 2814 NOE-derived distance constraints, and 272 torsion angle constraints derived from scalar couplings. A large number of critical inter-subunit NOEs (386) were identified from 13C-select, 13C-filtered NOESY experiments, providing a highly accurate dimer interface. The combination of distance geometry and restrained molecular dynamics calculations yielded structures with excellent agreement with the experimental data and high precision (rmsd from the mean for the backbone atoms in the eight helices: 0.33 A). Calcyclin exhibits a symmetric dimeric fold of two identical 90 amino acid subunits, characteristic of the S100 subfamily of EF-hand Ca(2+)-binding proteins. The structure reveals a readily identified pair of putative sites for binding of Zn2+. In order to accurately determine the structural features that differentiate the various S100 proteins, distance difference matrices and contact maps were calculated for the NMR structural ensembles of apo calcyclin and rat and bovine S100B. These data show that the most significant variations among the structures are in the positioning of helix III and in loops, the regions with least sequence similarity. Inter-helical angles and distance differences for the proteins show that the positioning of helix III of calcyclin is most similar to that of bovine S100B, but that the helix interfaces are more closely packed in calcyclin than in either S100B structure. Surprisingly large differences were found in the positioning of helix III in the two S100B structures, despite there being only four non-identical residues, suggesting that one or both of the S100B structures requires further refinement.

Inhibition evoked from primary afferents in the electrosensory lateral line lobe of the weakly electric fish (Apteronotus leptorhynchus).

Inhibition evoked from primary afferents in the electrosensory lateral line lobe of the weakly electric fish (Apteronotus leptorhynchus). J. Neurophysiol. 80: 3173-3196, 1998. The responses of two types of projection neurons of the electrosensory lateral line lobe, basilar (BP) and nonbasilar (NBP) pyramidal cells, to stimulation of primary electrosensory afferents were determined in the weakly electric fish, Apteronotus leptorhynchus. Using dyes to identify cell type, the response of NBP cells to stimulation of primary afferents was inhibitory, whereas the response of BP cells was excitation followed by inhibition. gamma-Aminobutyric acid (GABA) applications produced biphasic (depolarization then hyperpolarization) responses in most cells. GABAA antagonists blocked the depolarizing effect of GABA and reduced the hyperpolarizing effect. The GABAB antagonists weakly antagonized the hyperpolarizing effect. The early depolarization had a larger increase in cell conductance than the late hyperpolarization. The conductance changes were voltage dependent, increasing with depolarization. In both cell types, baclofen produced a slow small hyperpolarization and reduced the inhibitory postsynaptic potentials (IPSPs) evoked by primary afferent stimulation. Tetanic stimulation of primary afferents at physiological rates (100-200 Hz) produced strongly summating compound IPSPs (approximately 500-ms duration) in NBP cells, which were usually sensitive to GABAA but not GABAB antagonists; in some cells there remained a slow IPSP that was unaffected by GABAB antagonists. BP cells responded with excitatory or mixed excitatory + inhibitory responses. The inhibitory response had both a fast (approximately 30 ms, GABAA) and long-lasting slow phase (approximately 800 ms, mostly blocked by GABAA antagonists). In some cells there was a GABAA antagonist-insensitive slow IPSP (approximately 500 ms) that was sensitive to GABAB antagonists. Application of glutamate ionotropic receptor antagonists blocked the inhibitory response of NBP cells to primary afferent stimulation and the excitatory response of BP cells but enhanced the BP cell slow IPSP; this remaining slow IPSP was reduced by GABAB antagonists. Unit recordings in the granule cell layer and computer simulations of pyramidal cell inhibition suggested that the duration of the slow GABAA inhibition reflects the prolonged firing of GABAergic granule cell interneurons to primary afferent input. Correlation of the results with known GABAergic circuitry in the electrosensory lobe suggests that the GABAergic type 2 granule cell input to both pyramidal cell types is via GABAA receptors. The properties of the GC2 GABAA input are well suited to their putative role in gain control, regulation of phasicness, and coincidence detection. The slow GABAB IPSP evoked in BP cells is likely due to ovoid cell input to their basal dendrites.