Selective neuroinhibitory effects of taurine in slices of rat main olfactory bulb

Taurine is abundant in the main olfactory bulb, exceeding glutamate and GABA in concentration. In whole-cell patch-clamp recordings in rat olfactory bulb slices, taurine inhibited principal neurons, mitral and tufted cells. In these cells, taurine decreased the input resistance and caused a shift of the membrane potential toward the chloride equilibrium potential. The taurine actions were sustained under the blockade of transmitter release and were reversible and dose-dependent. At a concentration of 5 mM, typically used in this study, taurine showed 90% of its maximal effect. GABA(A) antagonists, bicuculline and picrotoxin, blocked the taurine actions, whereas the glycine receptor antagonist strychnine and GABA(B) antagonists, CGP 55845A and CGP 35348, were ineffective. These findings are consistent with taurine directly activating GABA(A) receptors and inducing chloride conductance. Taurine had no effect on periglomerular and granule interneurons. The subunit composition of GABA(A) receptors in these cells, differing from those in mitral and tufted cells, may account for taurine insensitivity of the interneurons. Taurine suppressed olfactory nerve-evoked monosynaptic responses of mitral and tufted cells while chloride conductance was blocked. This action was mimicked by the GABA(B) agonist baclofen and abolished by CGP 55845A; CGP 35348, which primarily blocks postsynaptic GABA(B) receptors, was ineffective. The taurine effect most likely was due to GABA(B) receptor-mediated inhibition of presynaptic glutamate release. Neither taurine nor baclofen affected responses of periglomerular cells. The lack of a baclofen effect implies that functional GABA(B) receptors are absent from olfactory nerve terminals that contact periglomerular cells. These results indicate that taurine decreases the excitability of mitral and tufted cells and their responses to olfactory nerve stimulation without influencing periglomerular and granule cells. Selective effects of taurine in the olfactory bulb may represent a physiologic mechanism that is involved in the inhibitory shaping of the activation pattern of principal neurons.     

Norepinephrine increases rat mitral cell excitatory responses to weak olfactory nerve input via alpha-1 receptors in vitro

A rat olfactory bulb in vitro slice preparation was used to investigate the actions of norepinephrine on spontaneous and afferent (olfactory nerve) evoked activity of mitral cells. Single olfactory nerve shocks elicited a characteristic mitral cell response consisting of distinct, early and late spiking components separated by a brief inhibitory epoch. Bath-applied norepinephrine (1 microM) increased the early spiking component elicited by perithreshold (79% increase, P<0.02), but not by suprathreshold (3% decrease, P>0.05), intensity olfactory nerve shocks. The facilitatory effect of norepinephrine was due to a reduction in the incidence of response failures to perithreshold intensity shocks. Norepinephrine also decreased the inhibitory epoch separating the early and late spiking components by 44% (P<0.05). By contrast, norepinephrine had no consistent effect on the spontaneous discharge rate of the mitral cells. The effects of norepinephrine were mimicked by the al receptor agonist phenylephrine (1 microM, P<0.001). Both norepinephrine and phenylephrine modulation of mitral cell responses were blocked by the al adrenergic antagonist WB-4101 (1 microM). These findings are consistent with observations that the main olfactory bulb exhibits the highest density of alpha1 receptors in the brain. The alpha2 receptor agonist clonidine (100 nM) and the beta receptor agonist isoproterenol (1 microM) had inconsistent effects on mitral cell spontaneous and olfactory nerve-evoked activity. These results indicate that norepinephrine increases mitral cell excitatory responses to weak but not strong olfactory nerve inputs in vitro via activation of al receptors. This is consistent with recent findings in vivo that synaptically released norepinephrine preferentially increases mitral cell excitatory responses to weak olfactory nerve inputs. Taken together, these results suggest that the release of norepinephrine in the olfactory bulb may increase the sensitivity of mitral cells to weak odors. Olfactory cues evoke norepinephrine release in the main olfactory bulb, and norepinephrine plays important roles in early olfactory learning and reproductive/maternal behaviors. By increasing mitral cell responses to olfactory nerve input, norepinephrine may play a critical role in modulating olfactory function, including formation and/or recall of specific olfactory memories.     

Activation of postsynaptic GABAB receptors modulates the bursting pattern and synaptic activity of olfactory bulb juxtaglomerular neurons

Olfactory bulb glomeruli are formed by a network of three major types of neurons collectively called juxtaglomerular (JG) cells, which include external tufted (ET), periglomerular (PG), and short axon (SA) cells. There is solid evidence that gamma-aminobutyric acid (GABA) released from PG neurons presynaptically inhibits glutamate release from olfactory nerve terminals via activation of GABA(B) receptors (GABA(B)-Rs). However, it is still unclear whether ET cells have GABA(B)-Rs. We have investigated whether ET cells have functional postsynaptic GABA(B)-Rs using extracellular and whole cell recordings in olfactory bulb slices. In the presence of fast synaptic blockers (CNQX, APV, and gabazine), the GABA(B)-R agonist baclofen either completely inhibited the bursting or reduced the bursting frequency and increased the burst duration and the number of spikes/burst in ET cells. In the presence of fast synaptic blockers and tetrodotoxin, baclofen induced an outward current in ET cells, suggesting a direct postsynaptic effect. Baclofen reduced the frequency and amplitude of spontaneous EPSCs in PG and SA cells. In the presence of sodium and potassium channel blockers, baclofen reduced the frequency of miniature EPSCs, which were inhibited by the calcium channel blocker cadmium. All baclofen effects were reversed by application of the GABA(B)-R antagonist CGP55845. We suggest that activation of GABA(B)-Rs directly inhibits ET cell bursting and decreases excitatory dendrodendritic transmission from ET to PG and SA cells. Thus the postsynaptic GABA(B)-Rs on ET cells may play an important role in shaping the activation pattern of the glomeruli during olfactory coding.     

Gabaergic control of olfactory learning in young rats.

Olfactory learning in young rats correlates with neural plasticity in the olfactory bulb, and involves noradrenergic modulation of reciprocal dendrodendritic synapses between mitral cells and GABAergic granule cells. The purpose of this study was to examine, in vivo, the consequences of manipulating bulbar GABA transmission during training. In the first experiment, postnatal day 11 rat pups were trained in an olfactory associative learning task with citral odor and foot shock as the conditioned and unconditioned stimuli, respectively. The pups received continuous infusion of saline or the GABA(A) receptor agonist muscimol into the olfactory bulbs throughout a 30-min training session. The pups were then tested on postnatal day 12 for a preference for or an aversion to citral odor. Saline-infused control pups developed an aversion to citral odor. The GABA(A) receptor agonist muscimol impaired this aversive learning in a dose-dependent manner. In the second experiment, pups were exposed to the odor for 30 min while receiving continuous intrabulbar infusion of a low or high dose of the GABA(A) receptor antagonist bicuculline, without any other reinforcer. Depending on whether a low (0.2 nmol/bulb) or high (1.0 nmol/bulb) dose of bicuculline was infused, the pups showed a preference or an aversion for citral odor after infusion of low and high doses, respectively. These results indicate that disinhibition of mitral cells in the olfactory bulb is critical for olfactory learning in young rats, and suggest that the degree of disinhibition is an important determinant in acquiring either preference or aversion for the conditioned odor.     

Tonic and synaptically evoked presynaptic inhibition of sensory input to the rat olfactory bulb via GABA(B) heteroreceptors

Olfactory receptor neurons of the nasal epithelium send their axons, via the olfactory nerve (ON), to the glomeruli of the olfactory bulb (OB), where the axon terminals form glutamatergic synapses with the apical dendrites of mitral and tufted cells, the output cells of the OB, and with juxtaglomerular (JG) interneurons. Many JG cells are GABAergic. Here we show that, despite the absence of conventional synapses, GABA released from JG cells activates GABA(B) receptors on ON terminals and inhibits glutamate release both tonically and in response to ON stimulation. Field potential recordings and current-source density analysis, as well as intracellular and whole cell recording techniques were used in rat OB slices. Baclofen (2-5 microM), a GABA(B) agonist, completely suppressed ON-evoked synaptic responses of both mitral/tufted cells and JG cells, with no evidence for postsynaptic effects. Baclofen (0.5-1 microM) also reversed paired-pulse depression (PPD) of mitral/tufted cell responses to paired-pulse facilitation (PPF), and reduced depression of JG cell excitatory postsynaptic currents (EPSCs) during repetitive ON stimulation. These results suggest that baclofen reduced the probability of glutamate release from ON terminals. The GABA(B) antagonists CGP35348 or CGP55845A increased mitral/tufted cell responses evoked by single-pulse ON stimulation, suggesting that glutamate release from ON terminals is tonically suppressed via GABA(B) receptors. The same antagonists reduced PPD of ON-evoked mitral/tufted cell responses at interstimulus intervals 50-400 ms. This finding suggests that a single ON impulse evokes sufficient GABA release, presumably from JG cells, to activate GABA(B) receptors on ON terminals. Thus GABA(B) heteroreceptors on ON terminals are activated by ambient levels of extrasynaptic GABA, and by ON input to the OB. The time course of ON-evoked, GABA(B) presynaptic inhibition suggests that neurotransmission to M/T cells and JG cells will be significantly suppressed when ON impulses arrive in glomeruli at 2.5-20 Hz. GABA(B) receptor-mediated presynaptic inhibition of sensory input to the OB may play an important role in shaping the activation pattern of the OB glomeruli during olfactory coding.     

Non-specific olfactory aversion induced by intrabulbar infusion of the GABA(A) receptor antagonist bicuculline in young rats

On postnatal day 12, young rats show an aversion to an odor to which they had been exposed along with presentations of foot shock on postnatal day 11. The acquisition of this aversive learning involves and requires disinhibition of the mitral/tufted cells induced by centrifugal noradrenergic activation during somatosensory stimulation. This olfactory learning is established only for the odor to which the rat has been exposed during conditioning. Infusion of the GABA(A) receptor antagonist bicuculline at a high dose (2.0 nmol/each olfactory bulb) into the olfactory bulb in the presence of an odor is capable of developing olfactory aversive responses without somatosensory stimulation in young rats. The purpose of this study is to characterize the properties of bicuculline-induced aversive responses. In contrast to the odor specificity of aversive learning produced by odor-shock conditioning, bicuculline-induced aversive responses lack odor specificity. Namely, bicuculline infusion in the presence of a citral odor results, in a dose-dependent manner, in subsequent aversive responses to strange odors (benzaldehyde and vanillin) that have never been presented. Moreover, bicuculline infusion alone is sufficient to produce dose-dependent aversive responses to strange odors (citral, benzaldehyde and geraniol).From these results we suggest that disinhibition of mitral/tufted cells from granule cells by bicuculline infusion makes young rats aversive to strange odors non-specifically, as if the rats had learned the odor aversion as a result of odor exposure paired with foot shock. Different mechanisms of disinhibition of the mitral/tufted cells may underlie both the pharmacological manipulation and noradrenergic activation by somatosensory stimulation.     

Control of the rat olfactory bulb activity induced by biologically significant odors (author's transl)

In acute experiments, unitary activity was recorded from mitral cells of the rat olfactory bulb. The animals were stimulated with odors that have been shown in previous experiments to give a distinct emotional behavior. In curarized rats an odor giving alarm behavior evoked a greater number of inhibitory than excitatory responses was elicited by a neutral odor. In rats under Nembutal anesthesia an alarming odor evoked a greater number of inhibitory than excitatory responses; a reassuring odor evoked a greater number of excitatory than inhibititory responses; and equal number of inhibitory and excitatory responses; a reassuring or a neutral odor evoked an equal number of inhibitory and excitatory responses. After sectioning the olfactory peduncles, the difference in ratio between excitatory and inhibitory responses for alarming or reassuring odors was no longer present. The results are discussed in terms of a modulation of mitral cell activity by higher nervous centers in relation to the biological significance of the stimulating odors.     

Intracellular responses of identified rat olfactory bulb interneurons to electrical and odor stimulation

1. Intracellular recordings were made from 28 granule cells and 6 periglomerular cells of the rat olfactory bulb during odor stimulation and electrical stimulation of the olfactory nerve layer (ONL) and lateral olfactory tract (LOT). Neurons were identified by injection of horseradish peroxidase (HRP) or biocytin and/or intracellular response characteristics. Odorants were presented in a cyclic sniff paradigm, as reported previously. 2. All interneurons could be activated from a wide number of stimulation sites on the ONL, with distances exceeding their known dendritic spreads and the dispersion of nerve fibers within the ONL, indicating that multisynaptic pathways must also exist at the glomerular region. All types of interneurons also responded to odorant stimulation, showing a variety of responses. 3. Granule cells responded to electrical stimulation of the LOT and ONL as reported previously. However, intracellular potential, excitability, and conductance analysis suggested that the mitral cell-mediated excitatory postsynaptic potential (EPSP) is followed by a long inhibitory postsynaptic potential (IPSP). An early negative potential, before the EPSP, was also observed in every granule cell and correlated with component I of the extracellular LOT-induced field potential. We have interpreted this negativity as a "field effect," that may be diagnostic of granule cells. 4. Most granule cells exhibited excitatory responses to odorant stimulation. Odors could produce spiking responses that were either nonhabituating (response to every sniff) or rapidly habituating (response to first sniff only). Other granule cells, while spiking to electrical stimulation, showed depolarizations that did not evoke spikes to odor stimulation. These depolarizations were transient with each sniff or sustained across a series of sniffs. These physiological differences to odor stimulation correlated with granule cell position beneath the mitral cell layer for 12 cells, suggesting that morphological subtypes of granule cells may show physiological differences. Some features of the granule cell odor responses seem to correlate with some of the features we have observed in mitral/tufted cell intracellular recordings. Only one cell showed inhibition to odors. 5. Periglomerular (PG) cells showed a response to ONL stimulation that was unlike that found in other olfactory bulb neurons. There was a long-duration hyperpolarization after a spike and large depolarization or burst of spikes (20-30 ms in duration). Odor stimulation produced simple bursts of action potentials, Odor stimulation produced simple bursts of action potentials, suggesting that PG cells may simply follow input from the olfactory nerve.(ABSTRACT TRUNCATED AT 400 WORDS)     

Optical imaging of odor preference memory in the rat olfactory bulb

Early olfactory preference learning in rat pups occurs when novel odors are paired with reinforcing tactile stimulation that activate the noradrenergic locus coeruleus. Pairing of odor and a noradrenergic agonist in the olfactory bulb is both necessary and sufficient for odor preference learning. This suggests the memory change occurs in the olfactory bulb. Previous electrophysiological experiments demonstrated that odor preference training induces an increase in the field excitatory postsynaptic potential to olfactory nerve input and an alteration, after training, in glomerular [14C]2- deoxyglucose uptake and in single-unit responses of principal cells. We investigate here whether, 24 h after olfactory preference training, there is an alteration in intrinsic optical signals at the glomerular level. Six-day-old rat pups were trained, as previously, for a peppermint odor preference. Trained pups and control littermates were subjected to imaging of odor-induced intrinsic optical signals 1 day after the training session. Trained pups exhibited significantly larger responses to the peppermint compared with untrained littermates previously exposed to the same odor. The response of trained pups to a control odor (amyl acetate) was, however, not significantly different from that of untrained littermates. These observations demonstrate that odor preference memory can be read-out by optical imaging techniques.     

Serotonin modulates the population activity profile of olfactory bulb external tufted cells

Serotonergic neurons in the raphe nuclei constitute one of the most prominent neuromodulatory systems in the brain. Projections from the dorsal and median raphe nuclei provide dense serotonergic innervation of the glomeruli of olfactory bulb. Odor information is initially processed by glomeruli, thus serotonergic modulation of glomerular circuits impacts all subsequent odor coding in the olfactory system. The present study discloses that serotonin (5-HT) produces excitatory modulation of external tufted (ET) cells, a pivotal neuron in the operation of glomerular circuits. The modulation is due to a transient receptor potential (TRP) channel-mediated inward current induced by activation of 5-HT(2A) receptors. This current produces membrane depolarization and increased bursting frequency in ET cells. Interestingly, the magnitude of the inward current and increased bursting inversely correlate with ET cell spontaneous (intrinsic) bursting frequency: slower bursting ET cells are more strongly modulated than faster bursting cells. Serotonin thus differentially impacts ET cells such that the mean bursting frequency of the population is increased. This centrifugal modulation could impact odor processing by: 1) increasing ET cell excitatory drive on inhibitory neurons to increase presynaptic inhibition of olfactory sensory inputs and postsynaptic inhibition of mitral/tufted cells; and/or 2) coordinating ET cell bursting with exploratory sniffing frequencies (5-8 Hz) to facilitate odor coding.     

Ketamine and MK801 attenuate paired pulse inhibition in the olfactory bulb of the rat

Summary We have investigated the effects of the phencyclidine like-compounds ketamine and MK801 on the evoked field potentials of rat olfactory bulb. Low doses of ketamine (3–6 mg/kg) blocked the inhibition of mitral cells by granule cells evoked by stimulation of lateral olfactory tract fibres or by stimulation of olfactory nerve. This blockade was not accompanied by a decrease in granule cell excitation as revealed by field potential recording. MK801 had a similar effect on the inhibition of mitral cells evoked by stimulation of the lateral olfactory tract. As ketamine does not influence the inhibitory action of GABA (Anis et al. 1983) these results suggest that both ketamine and MK801 block inhibition by an action on intrinsic excitatory feed-back circuits in the olfactory bulb.     

Increased dopamine after mating impairs olfaction and prevents odor interference with pregnancy

In rodents, social odor sensing influences female reproductive status by affecting neuroendocrine cascades. The odor of male mouse urine can induce ovulation or block pregnancy within 3 d post coitus. Females avoid the action of such olfactory stimuli after embryonic implantation. The mechanisms underlying these changes are unknown. Here we report that shortly after mating, a surge in dopamine in the mouse main olfactory bulb impairs the perception of social odors contained in male urine. Treatment of females at 6.5 d post coitus with a dopamine D2 receptor antagonist restores social odor sensing and favors disruption of pregnancy by inhibition of prolactin release, when administered in the presence of alien male urine odors. These results show that an active sensory barrier blocks social olfactory cues detrimental to pregnancy, consistent with the main olfactory bulb being a major relay through which social odor modulates reproductive status.     

Lateral inhibition in the olfactory bulb and in olfaction

Lateral inhibition in the olfactory bulb is mediated by circuits that involve reciprocal dendrodendritic connections between mitral and granule cells. Because of the properties of these connections and also because odor stimuli are not represented in an obviously topographic fashion, questions have been raised about whether the function of local inhibition in the olfactory bulb can be compared to the function of inhibition in other brain areas. Here, I propose an analysis of local inhibition in the olfactory bulb based on the simplification that olfactory bulb circuitry can be thought of as implementing a simple linear two-dimensional filter. This analysis highlights some important characteristics of the circuitry of the olfactory bulb and suggests that the function of lateral inhibition in the olfactory bulb may be to compensate for generalized, spatially distributed activation that otherwise may obscure the specific, discrete patterns of glomerular activation seen across the olfactory bulb.     

Mitral cell temporal response patterns evoked by odor mixtures in the rat olfactory bulb

Mammals generally have the ability to extract odor information contained in complex mixtures of molecular components. However, odor mixture processing has been studied electrophysiologically only in insects, crustaceans, and fish. As a first step toward a better understanding of this processing in high vertebrates, we studied the representation of odor mixtures in the rat olfactory bulb, i.e., the second-order level of the olfactory pathways. We compared the single-unit responses of mitral cells, the main cells of the olfactory bulb, to pure odors and to their binary mixtures. Eighty-six mitral cells were recorded in anesthetized freely breathing rats stimulated with five odorants and their 10 binary mixtures. The spontaneous activity and the odor-evoked responses were characterized by their temporal distribution of activity along the respiratory cycle, i.e., by cycle-triggered histograms. Ninety percent of the mixtures were found to evoke a response when at least one of their two components evoked a response. Mixture-evoked patterns were analyzed to describe the modalities of the combination of patterns evoked by the two components. In most of the cases, the mixture pattern was closely similar to one of the component patterns. This dominance of a component over the other one was related to the responsiveness of the cell to the individual components of the mixture, to the molecular nature of the stimulus, and to the coarse shape of individual response patterns. This suggests that the components of binary mixtures may be encoded simultaneously by different odor-specific temporal distributions of activity.     

Endogenous GABA and glutamate finely tune the bursting of olfactory bulb external tufted cells

In rat olfactory bulb slices, external tufted (ET) cells spontaneously generate spike bursts. Although ET cell bursting is intrinsically generated, its strength and precise timing may be regulated by synaptic input. We tested this hypothesis by analyzing whether the burst properties are modulated by activation of ionotropic gamma-aminobutyric acid (GABA) and glutamate receptors. Blocking GABA(A) receptors increased--whereas blocking ionotropic glutamate receptors decreased--the number of spikes/burst without changing the interburst frequency. The GABA(A) agonist (isoguvacine, 10 microM) completely inhibited bursting or reduced the number of spikes/burst, suggesting a shunting effect. These findings indicate that the properties of ET cell spontaneous bursting are differentially controlled by GABAergic and glutamatergic fast synaptic transmission. We suggest that ET cell excitatory and inhibitory inputs may be encoded as a change in the pattern of spike bursting in ET cells, which together with mitral/tufted cells constitute the output circuit of the olfactory bulb.     

Spatial patterns of olfactory bulb single-unit responses to learned olfactory cues in young rats

1. Neonatal rat pups were classically conditioned to an odor stimulus from postnatal day 1 (PN1) to PN18. Tactile stimulation (stroking) was used as the unconditioned stimulus. On PN19, mitral/tufted cell single-unit responses to the conditioned odor were examined in both conditioned and control pups. Recordings were made from mitral/tufted cells in two regions of the olfactory bulb: 1) an area typically associated with focal [14C]2-deoxyglucose (2-DG) uptake in response to the conditioned odor and 2) an area distant from focal 2-DG uptake to the conditioned odor. Animals were anesthetized with urethane and were naturally respiring during the single-unit recording procedure. 2. Changes in mitral/tufted cell firing rate in response to odors in both bulbar regions and all training groups were classified as either excitatory, suppressive, or no response. This response classification was used to compare response patterns to the conditioned odor between bulbar regions and training groups. 3. Classical conditioning selectively modified the response patterns of mitral/tufted cells to the conditioned odor when those cells were associated with regions of focal 2-DG uptake for that odor. Mitral/tufted cells demonstrated significantly more suppressive and fewer excitatory responses to the conditioned odor than cells in control pups. Response patterns to a novel odor were not similarly modified. 4. Response patterns of mitral/tufted cells distant from the focal region of 2-DG uptake to the conditioned odor were not modified by conditioning compared with control pups. 5. The difference in response pattern between cells in the 2-DG focus and cells distant to the 2-DG focus was apparent within 500 ms of the stimulus onset. Given the respiratory rate of these pups (2 Hz), these data suggest that the modified response pattern occurred on the first inhalation of the learned odor. 6. These data demonstrate that both spatial and temporal patterns of olfactory bulb output neuron activity are used in the coding of olfactory information in the bulb. Furthermore, these spatial/temporal response patterns can be modified by early learning.     

Inhibition of backpropagating action potentials in mitral cell secondary dendrites

The mammalian olfactory bulb is a geometrically organized signal-processing array that utilizes lateral inhibitory circuits to transform spatially patterned inputs. A major part of the lateral circuitry consists of extensively radiating secondary dendrites of mitral cells. These dendrites are bidirectional cables: they convey granule cell inhibitory input to the mitral soma, and they conduct backpropagating action potentials that trigger glutamate release at dendrodendritic synapses. This study examined how mitral cell firing is affected by inhibitory inputs at different distances along the secondary dendrite and what happens to backpropagating action potentials when they encounter inhibition. These are key questions for understanding the range and spatial dependence of lateral signaling between mitral cells. Backpropagating action potentials were monitored in vitro by simultaneous somatic and dendritic whole cell recording from individual mitral cells in rat olfactory bulb slices, and inhibition was applied focally to dendrites by laser flash photolysis of caged GABA (2.5-microm spot). Photolysis was calibrated to activate conductances similar in magnitude to GABA(A)-mediated inhibition from granule cell spines. Under somatic voltage-clamp with CsCl dialysis, uncaging GABA onto the soma, axon initial segment, primary and secondary dendrites evoked bicuculline-sensitive currents (up to -1.4 nA at -60 mV; reversal at approximatety 0 mV). The currents exhibited a patchy distribution along the axon and dendrites. In current-clamp recordings, repetitive firing driven by somatic current injection was blocked by uncaging GABA on the secondary dendrite approximately 140 microm from the soma, and the blocking distance decreased with increasing current. In the secondary dendrites, backpropagated action potentials were measured 93-152 microm from the soma, where they were attenuated by a factor of 0.75 +/- 0.07 (mean +/- SD) and slightly broadened (1.19 +/- 0.10), independent of activity (35-107 Hz). Uncaging GABA on the distal dendrite had little effect on somatic spikes but attenuated backpropagating action potentials by a factor of 0.68 +/- 0.15 (0.45-0.60 microJ flash with 1-mM caged GABA); attenuation was localized to a zone of width 16.3 +/- 4.2 microm around the point of GABA release. These results reveal the contrasting actions of inhibition at different locations along the dendrite: proximal inhibition blocks firing by shunting somatic current, whereas distal inhibition can impose spatial patterns of dendrodendritic transmission by locally attenuating backpropagating action potentials. The secondary dendrites are designed with a high safety factor for backpropagation, to facilitate reliable transmission of the outgoing spike-coded data stream, in parallel with the integration of inhibitory inputs.     

Self-inhibition of olfactory bulb neurons

The GABA (gamma-aminobutyric-acid)-containing periglomerular (PG) cells provide the first level of inhibition to mitral and tufted (M/T) cells, the output neurons of the olfactory bulb. We find that stimulation of PG cells of the rat olfactory bulb results in self-inhibition: release of GABA from an individual PG cell activates GABA(A) receptors on the same neuron. PG cells normally contain high concentrations of intracellular chloride and consequently are depolarized by GABA. Despite this, GABA inhibits PG cell firing by shunting excitatory signals. Finally, GABA released during self-inhibition may spill over to neighboring PG cells, resulting in a lateral spread of inhibition. Given the gatekeeping role of PG cells in the olfactory network, GABA-mediated self-inhibition will favor M/T cell excitation during intense sensory stimulation.     

Multiple site optical recording of transmembrane voltage (MSORTV), single-unit recordings, and evoked field potentials from the olfactory bulb of skate (Raja erinacea)

1. Multiple site optical recording of transmembrane voltage (MSORTV), together with conventional extracellular electrophysiological techniques were utilized with in vivo and in vitro preparations of the olfactory bulb of the Atlantic skate Raja erinacea to analyze electrical activity simultaneously in layers deep to the glomerular layer. 2. In the living animals and the in vitro isolated olfactory bulb, orthodromic stimulation evoked a compound action potential in the olfactory nerve fibers, followed by a series of early field-potential waves (N1, P1, N2, P2, N3, and N4). During paired stimulation experiments, unusual patterns of facilitation and suppression were observed for the N2 wave. 3. After orthodromic stimulation, single units, presumably mitral/tufted cells, exhibited a period of early discharge, followed by a period of suppression of spontaneous activity and of their test response in a pair stimulation paradigm. Some neurons also exhibited a labile period of reexcitation that was accompanied by a late surface negative field potential; these responses were also present in olfactory bulb slices. 4. Extrinsic absorption changes obtained from 500-microns saggital slices of the olfactory bulb, stained with the pyrazooxonal dye RH-155, consisted mainly of two types of depolarizing responses, a fast and a slow component, followed under some conditions by a late hyperpolarization. All signals exhibited wavelength dependences typical of the action spectrum of RH-155 and were abolished in the presence of tetrodotoxin (TTX) or high K+ in the bath. 5. The fast component of the optical signal represents synchronous compound action potentials conducted by the olfactory nerve fibers or evoked in the mitral/tufted somata and axonal pathways. The slow depolarizing optical signal appeared, after orthodromic stimuli, mainly in the zone between the glomeruli and the mitral/tufted layer; barium (1-10 mM), which depolarizes glial cells, increased its size and duration, suggesting that this signal does not reflect a glial response to [K+]o. 6. Different condition/test (C/T) intervals produced partial or complete suppression of the test response, depending on the recording site and the stimulus intensity. Just threshold orthodromic stimuli evoked an intermediate period of facilitation of the slow signals. A similar period was also observed in the N2 wave of the field potential. 7. Calcium channel blockers such as cadmium ion, or a low Ca2+ medium, suppressed the slow optical component whether evoked by orthodromic, antidromic, or direct stimulation. gamma-Aminobutyric acid (GABA) and baclofen also reduced or blocked the slow component of the extrinsic absorption signal.(ABSTRACT TRUNCATED AT 400 WORDS)