Lateral Inhibitory Effects Research Articles

Spatio-Temporal Characteristics of Inhibition Mapped by Optical Stimulation in Mouse Olfactory Bulb.

Mitral and tufted cells (MTCs) of the mammalian olfactory bulb are connected via dendrodendritic synapses with inhibitory interneurons in the external plexiform layer. The range, spatial layout, and temporal properties of inhibitory interactions between MTCs mediated by inhibitory interneurons remain unclear. Therefore, we tested for inhibitory interactions using an optogenetic approach. We optically stimulated MTCs expressing channelrhodopsin-2 in transgenic mice, while recording from individual MTCs in juxtacellular or whole-cell configuration in vivo. We used a spatial noise stimulus for mapping interactions between MTCs belonging to different glomeruli in the dorsal bulb. Analyzing firing responses of MTCs to the stimulus, we did not find robust lateral inhibitory effects that were spatially specific. However, analysis of sub-threshold changes in the membrane potential revealed evidence for inhibitory interactions between MTCs that belong to different glomerular units. These lateral inhibitory effects were short-lived and spatially specific. MTC response maps showed hyperpolarizing effects radially extending over more than five glomerular diameters. The inhibitory maps exhibited non-symmetrical yet distance-dependent characteristics.

Glomerular interactions in olfactory processing channels of the antennal lobes.

An open question in olfactory coding is the extent of interglomerular connectivity: do olfactory glomeruli and their neurons regulate the odorant responses of neurons innervating other glomeruli? In the olfactory system of the moth Manduca sexta, the response properties of different types of antennal olfactory receptor cells are known. Likewise, a subset of antennal lobe glomeruli has been functionally characterized and the olfactory tuning of their innervating neurons identified. This provides a unique opportunity to determine functional interactions between glomeruli of known input, specifically, (1) glomeruli processing plant odors and (2) glomeruli activated by antennal stimulation with pheromone components of conspecific females. Several studies describe reciprocal inhibitory effects between different types of pheromone-responsive projection neurons suggesting lateral inhibitory interactions between pheromone component-selective glomerular neural circuits. Furthermore, antennal lobe projection neurons that respond to host plant volatiles and innervate single, ordinary glomeruli are inhibited during antennal stimulation with the female's sex pheromone. The studies demonstrate the existence of lateral inhibitory effects in response to behaviorally significant odorant stimuli and irrespective of glomerular location in the antennal lobe. Inhibitory interactions are present within and between olfactory subsystems (pheromonal and non-pheromonal subsystems), potentially to enhance contrast and strengthen odorant discrimination.

Dynamics about neural array with simple lateral inhibitory connections

Lateral inhibitory effect is a well-known feature of information processing in neural systems. This paper presents a neural array model with simple lateral inhibitory connections. After detailed examining into the dynamics of this kind of neural array, the author gives the sufficient conditions under which the outputs of the network will tend to a special stable pattern called spatial sparse pattern in which if the output of a neuron is 1, then the outputs of the neurons in its neighborhood are 0. This ability called spatial sparse coding plays an important role in self-coding, self-organization and associative memory for patterns and pattern sequences. The main conclusions about the dynamics of this kind of neural array which is related to spatial sparse coding are introduced.

Inhibitory impact of subliminal electrical finger stimulation on SI representation and perceptual sensitivity of an adjacent finger

Simultaneous stimulation of two adjacent fingers above sensory perception threshold (supraliminal stimulation) leads to an inhibitory interaction effect on responses in primary somatosensory cortex (SI). Moreover, during electrical finger stimulation closely below threshold for conscious perception (subliminal stimulation) inhibitory interneurons in cortical layer 4 are assumed to be activated preferentially as compared to excitatory interneurons. Using fMRI in humans, here we show that interspersed subliminal electrical stimulation of an adjacent finger reduces the response to target finger stimulation in contralateral SI. This effect was shown in a complementary study to be associated behaviorally with a diminished detectability of test pulses on the target finger. We propose the mechanism underlying this lateral inhibitory effect to be related to a representational overlap of inhibitory interneurons in SI based on the divergence of thalamocortical feedforward projections, or to intracortical lateral inhibitory projections targeting juxtaposed receptive fields, or both.

Coherent ongoing subthreshold state of a cortical neural network regulated by slow- and fast-spiking interneurons

Although details of cortical interneurons in anatomy and physiology have been well understood, little is known about how they contribute to ongoing spontaneous neuronal activity that could have a great impact on subsequent neuronal information processing. Simulating a cortical neural network model of an early sensory area, we investigated whether and how two distinct types of inhibitory interneurons, or fast-spiking interneurons with narrow axonal arbors and slow-spiking interneurons with wide axonal arbors, have a spatiotemporal influence on the ongoing activity of principal cells and subsequent cognitive information processing. In the model, dynamic cell assemblies, or population activation of principal cells, expressed information about specific sensory features. Within cell assemblies, fast-spiking interneurons give a feedback inhibitory effect on principal cells. Between cell assemblies, slow-spiking interneurons give a lateral inhibitory effect on principal cells. Here, we show that these interneurons keep the network at a subthreshold level for action potential generation under the ongoing state, by which the reaction time of principal cells to sensory stimulation could be accelerated. We suggest that the best timing of inhibition mediated by fast-spiking interneurons and slow-spiking interneurons allows the network to remain near threshold for rapid responses to input.

Amplitude-dependency of response of SI cortex to flutter stimulation

BackgroundIt is established that increasing the amplitude of a flutter stimulus increases its perceived intensity. Although many studies have examined this phenomenon with regard to the responding afferent population, the way in which the intensity of a stimulus is coded in primary somatosensory cortex (SI) remains unclear.ResultsOptical intrinsic signal (OIS) imaging was used to study the evoked responses in SI of anesthetized squirrel monkeys by 25 Hz sinusoidal vertical skin displacement stimulation. Stimuli were 10 sec duration with a 50 sec inter-stimulus interval. Stimulus amplitude ranged from 50 to 400 microns and different amplitudes were interleaved. Control levels of activity were measured in the absence of stimulation, and used to compare with activation levels evoked by the different stimulus amplitudes. Stimulation of a discrete skin site on the forelimb evoked a prominent increase in absorbance within the forelimb representational region in cytoarchitectonic areas 3b and 1 of the contralateral hemisphere. An increase in stimulus amplitude led to a proportional increase in the magnitude of the absorbance increase in this region of areas 3b and 1 while surrounding cortex underwent a decrease in absorbance. Correlation maps revealed that as stimulus amplitude is increased, the spatial extent of the activated region in SI remains relatively constant, and the activity within this region increases progressively. Additionally, as stimulus amplitude is increased to suprathreshold levels, activity in the surround of the activated SI territory decreases, suggesting an increase in inhibition of neuronal activity within these regions.ConclusionIncreasing the amplitude of a flutter stimulus leads to a proportional increase in absorbance within the forelimb representational region of SI. This most likely reflects an increase in the firing rate of neurons in this region of SI. The relatively constant spatial extent of this stimulus-evoked increase in absorbance suggests that an increase in the amplitude of a 25 Hz skin stimulus does not evoke a larger area of SI neuronal activation due to an amplitude-dependent lateral inhibitory effect that spatially funnels the responding SI neuronal population.

Speed of pattern appearance in reaction-diffusion models: implications in the pattern formation of limb bud mesenchyme cells

It has been postulated that fibroblast growth factor (FGF) treatment of cultured limb bud mesenchyme cells reinforces the lateral inhibitory effect, but the cells also show accelerated pattern appearance. In the present study, we analyze how a small change in a specific parameter affects the speed of pattern appearance in a Turing reaction-diffusion system using linear stability analysis. It is shown that the sign of the change in appearance speed is qualitatively decided if the system is under the diffusion-driven instability condition, and this is confirmed by numerical simulations. Numerical simulations also show that a small change in parameter value induced easily detectable differences in the appearance speed of patterns. Analysis of the Gierer–Meinhardt model revealed that a change in a single parameter can explain two effects of FGF on limb mesenchyme cells—reinforcement of lateral inhibition and earlier appearance of pattern. These qualitative properties and easy detectability make this feature a promising tool to elucidate the underlying mechanisms of biological pattern formation where the quantitative parameters are difficult to obtain.

Sensitivity of human auditory evoked potentials to the harmonicity of complex tones: evidence for dissociated cortical processes of spectral and periodicity analysis.

A strong subjective tendency exists for simultaneous sound frequencies forming an harmonic series (integer multiples of the fundamental) to "group" together into a unified auditory percept whose pitch is similar to that of the fundamental. The aim of the study was to determine whether cortical auditory evoked potentials (AEPs) to complex tones differ according to whether the component frequencies of the stimuli are harmonically related or not. AEPs were recorded to continuous complex tones comprising four or more sinusoids. The vertex-maximal "change-potentials" (CP1, CN1, CP2), recorded to a stimulus cycle comprising one harmonic and five inharmonic complexes changing every second, showed no sensitivity to harmonicity, although an additional mismatch negativity was possibly present to the harmonic complex. In a second study the CP2 was significantly attenuated when an harmonic complex changed to a new one in the presence of an unchanging sinusoidal background tone, harmonically related to the first complex but not to the second, and thus becoming perceptually distinct. This, however, might be caused by lateral inhibitory effects not related to harmonicity. In a third experiment, when four concurrent sinusoidal tones came to rest on steady frequencies after a 5-s period of 16/s pseudo-random frequency changes, fronto-centrally maximal "mismatch-potentials" (MN1, MP2), were recorded. Both the MN1 and the MP2 were significantly shorter in latency when the steady frequencies formed an harmonic complex. Since the harmonic complex had a short overall periodicity, equal to that of the fundamental, while that of the inharmonic complex was much longer, the effect might be explained if the latencies of the mismatch-potential are related to periodicity. The perceptual grouping of harmonically related frequencies appears not to be a function of spectral domain analysis, reflected in the change-potentials, but of periodicity analysis, reflected in the mismatch-potentials

Depletion of FGF acts as a lateral inhibitory factor in lung branching morphogenesis in vitro

Previous studies have shown that the interaction of positive and inhibitory signals plays a crucial role during lung branching morphogenesis. We found that in mesenchyme-free conditions, the lung epithelium exerted a lateral inhibitory effect on the neighbouring epithelium via depletion of fibroblast growth factor 1 (FGF1). Contrary to previous suggestions, bone morphogenetic protein 4 could not substitute for the inhibitory effect. Based on of this observation, we used a reaction–diffusion model of the substrate-depletion type to represent the initial phase of in vitro branching morphogenesis of lung epithelium, with depletion of FGF playing the role of lateral inhibitor. The model was able to account for the effects of the FGF1 concentration, extracellular matrix degradation and different subtypes of FGF on morphogenesis of the lung bud epithelia. These results suggest that the depletion of FGF may be a key regulatory component in initial phase of branching morphogenesis of the lung bud epithelium in vitro.

Retinal Mechanisms in the Perception of Subjective Contours: The Contribution of Lateral Inhibition

One mechanism frequently proposed for the creation of subjective contours and their related brightness effects involves lateral neural interactions on the retina, such as the lateral inhibitory effects that underlie brightness contrast. Subjective contour stimuli were displayed under an intermittent light source, with rapid onset and slow offset as has been shown to increase lateral inhibitory interactions by allowing summation of neural onset transients. A sample of forty subjects, using magnitude estimates, reported increased subjective contour clarity and brightness effects under these exposure conditions. The effects were larger for relative brightness differences than for contour visibility. It appears that this technique may have applications in exploring retinal contributions to other aspects of the perception of subjective contours.

Analysis of visual modulation sensitivity IV Validity of the Ferry–Porter law

The maximum flicker frequency was determined over a 5+6-log-unit range of retinal illuminance for a stimulus configuration designed to isolate the linear response from long-wavelength (R) cones. For a particular retinal location, the data conformed to the Ferry-Porter law and departed significantly from the predictions of the diffusion equation. The slope of the function was an invariant characteristic and was unaffected by stimulus intensity or area, modulation waveform, or modulation amplitude. However, the slope varied substantially with retinal locus, increasing by more than a factor of 2 between the foveola and 35 degrees eccentricity. This increase shows that the time constant of the linear, unadapted visual response decreases with increasing eccentricity. The difference between foveola and periphery remained at high spatial frequencies, implying that it was not attributable to lateral inhibitory effects.

The interplexiform-horizontal cell system of the fish retina: effects of dopamine, light stimulation and time in the dark.

Interplexiform cells contact cone horizontal cells in the fish retina and probably release dopamine at synaptic sites. The effects of dopamine, certain related compounds, and light and dark régimes were tested on the intracellularly recorded activity of horizontal cells in the superfused carp retina to elucidate the functional role of the interplexiform cell. Dopamine application onto retinae kept in the dark for 30-40 min increased the size of the responses of cone horizontal cells to small-spot stimuli but decreased response size to large- and full-field stimuli. Dopamine also altered the response waveform of these cells; the transient at response onset increased in size and the depolarizing afterpotential decreased in size. Haloperidol, a dopamine antagonist, blocked these effects of dopamine application. Forskolin, an adenylate cyclase activator, increased the size of the responses of the cells to small-spot stimuli. Superfusion of vasoactive intestinal peptide did not produce any effects on horizontal cells. The results indicate that dopamine produces multiple physiological effects on cone horizontal cells by activation of an intracellular enzyme system. We propose that some of these effects are probably related to an uncoupling of the gap junctions between horizontal cells, but that other effects are most likely not explained on this basis and reflect additional changes induced in the cells by dopamine. After prolonged periods of darkness (100-110 min), compared with short periods (30-40 min), L-type cone horizontal cells exhibited responses similar to those obtained during dopamine application. Dim flickering or continuous light backgrounds did not mimic the effects of dopamine. Although dopamine application onto retinae after short-term darkness produced dramatic effects on L-type cone horizontal cells, little or no effect was observed when dopamine was applied while the effects of a previous dopamine application were still present or after prolonged darkness. These results suggest that interplexiform cells may release dopamine after prolonged darkness and that interplexiform cells may regulate lateral inhibitory effects mediated by L-type cone horizontal cells as a function of time in the dark.

Synaptic organization of the dopaminergic neurons in the rabbit retina

AbstractA number of substances were tested for their ability to label amine‐accumulating neurons in the rabbit retina after fixation with OsO4 or glutaraldehyde and OsO4. Useful results were obtained with 5,6‐dihydroxytryptamine (5,6‐DHT) and 6‐hydroxydopamine (6‐HDA). Labelled processes were characterized by small (40–50 mm) pleomorphic synaptic vesicles containing electron‐dense cores, and at times by swelling of mitochondria and by increased electron density of membranes and cytoplasm. Fluorescence microscopy showed that 5,6‐DHT labelled both dopaminergic and indoleamine‐accumulating neurons. In most experiments, therefore, the indoleamine‐accumulating neurons were removed with 5,7‐dihydroxytryptamine. In such retinas the dopaminergic processes labelled by 5,6‐DHT were found to make synapses of the conventional type, characterized by an accumulation of synaptic vesicles on the presumed presynaptic side and some aggregation of material on the cytoplasmic side of the synaptic membranes and within the synaptic cleft. The dopaminergic processes were found to contact each other and also non‐dopaminergic amacrine cells and their processes. Conventional synapses onto dopaminergic processes were observed from both labelled and unlabelled amacrine processes. The input from labelled neurons was observed on varicose dopaminergic processes whereas input from non‐labelled elements was found on the intervaricose parts of the dopaminergic processes. No Contacts of dopaminergic processes with bipolar or ganglion cells were observed. Injections of 6‐HDA gave the same results, although this drug gave less distinct labelling which made the observations less decisive than with 5,6‐DHT. In retinas treated with 5,6‐DHT alone (i.e., in which the indoleamine‐accumulating neurons remained) numerous processes were observed which were both pre‐ and postsynaptic to bipolar terminals. These observations suggest that the indoleamine‐accumulating processes synapse with bipolar cells.The results show that the dopaminergic neurons form a network involving only amacrine cells, suggesting a regulatory function for them. By analogy with the dopaminergic interplexiform cells of the goldfish retina, it is suggested that the dopaminergic neurons in the rabbit may regulate lateral inhibitory effects mediated by amacrine cells. Furthermore, the finding that the dopaminergic and indoleamine‐accumulating cells apparently have a different synaptic organization suggests that it is appropriate to categorize amacrine cells according to their transmitter content as well as their morphology.

The interplexiform cell system. II. Effects of dopamine on goldfish retinal neurones.

The effects of atomized solutions of dopamine and certain related com­pounds have been tested on the intracellularly recorded activity of receptor, horizontal, bipolar and amacrine cells in the goldfish retina. Dopamine depolarizes the cone L-type horizontal cells and reduces the amplitude of light-evoked responses. These effects on L-type horizontal cells are completely abolished by the α-adrenergie blocker, phentolamine, but only partially depressed by the β-blocker, propanolol. L-Dopa, noradrenalin, and serotonin do not have effects on L-type horizontal cells when applied at concentrations similar to those that cause maximal dopamine effects. The results suggest that the effects of dopamine on L-type horizontal cells are specific, and we propose that they mimic the effects of interplexiform cell activity. Dopamine has no effects on rod horizontal cells in goldfish and variable effects on C-type horizontal cells. On bipolar cells, dopamine alters the dark membrane potential, enhances the central response to light, and depresses the surround response. Dopamine also decreases the horizontal cell feedback evident in cone responses. Finally, dopamine strongly depolarizes the transient type of amacrine cells, but it has no significant effect on the sustained type of amacrine cells. Assuming that dopamine is the transmitter of interplexiform cells, we suggest that these neurons regulate lateral inhibitory effects mediated by L-type horizontal cells in the outer plexiform layer and transient amacrine cells in the inner plexiform layer. In addition, it appears as if interplexiform cells have specific effects on bipolar cells and are capable of regulating centre-surround antagonism in these cells. The net effect of interplexiform cell activity is to isolate the bipolars from the influence of the surround.

Visual sensitivity at an edge

The threshold for a small spot of light rises as it approaches the edge of an illuminated area and gradually falls in the dark. The threshold rise on the illuminated side of the edge was found to be dependent on the intensity of the illuminated field, absent at low in tensity. Short duration flashes of both edge and test spot abolished the threshold elevation on the illuminated side of the edge regardless of field intensity. While the threshold rise may be associated with lateral inhibitory effects, the fall in the dark was shown to be due to stray light in the eye.

The effect of texture oil the magnitude of

The magnitude of simultaneous brightness contrast was measured while the coarseness of the textural overlay was varied. Remits from 10 Ss indicate that as the size of elements in the texture increases, the amount of obtained contrast decreases. An interpretation of these results in terms of the spread of lateral inhibitory effects is offered.

Area effects and the rapid threshold decrease in early dark adaptation.

At the beginning of dark adaptation there is a sudden decrease of threshold that appears distinct from the subsequent course of regular dark adaptation. The present research indicates that the decrease cannot be a result of losing the lateral inhibitory effects that occurred during the light adaptation prior to dark adaptation. The results thus imply that the early threshold drop must be based on a process somewhere in the direct line from receptor to higher centers.

The perception of color with achromatic stimulation

A series of experiments demonstrated that the flicker colors can be produced by appropriate changes in the intensity of a stationary light source. If the intensity changes resemble those produced by a Benham Top, then lateral inhibitory effects from a flickering background must be present to produce the colors. Patterns of temporal intensity changes were discovered by means of which the flicker colors were produced with a constant background.