Strong Lateral Inhibition Research Articles

A Characterization of the Electrophysiological and Morphological Properties of Vasoactive Intestinal Peptide (VIP) Interneurons in the Medial Entorhinal Cortex (MEC).

Circuit interactions within the medial entorhinal cortex (MEC) translate movement into a coherent code for spatial location. Entorhinal principal cells are subject to strong lateral inhibition, suggesting that a disinhibitory mechanism may drive their activation. Cortical Vasoactive Intestinal Peptide (VIP) expressing inhibitory neurons are known to contact other interneurons and excitatory cells and are thus capable of providing a local disinhibitory mechanism, yet little is known about this cell type in the MEC. To investigate the electrophysiological and morphological properties of VIP cells in the MEC, we use in vitro whole-cell patch-clamp recordings in VIPcre/tdTom mice. We report several gradients in electrophysiological properties of VIP cells that differ across laminae and along the dorsal-ventral MEC axis. We additionally show that VIP cells have distinct morphological features across laminae. Together, these results characterize the cellular and morphological properties of VIP cells in the MEC.

Maximized lateral inhibition in paired magnetic domain wall racetracks for neuromorphic computing

Lateral inhibition is an important functionality in neuromorphic computing, modeled after the biological neuron behavior that a firing neuron deactivates its neighbors belonging to the same layer and prevents them from firing. In most neuromorphic hardware platforms lateral inhibition is implemented by external circuitry, thereby decreasing the energy efficiency and increasing the area overhead of such systems. Recently, the domain wall—magnetic tunnel junction (DW-MTJ) artificial neuron is demonstrated in modeling to be intrinsically inhibitory. Without peripheral circuitry, lateral inhibition in DW-MTJ neurons results from magnetostatic interaction between neighboring neuron cells. However, the lateral inhibition mechanism in DW-MTJ neurons has not been studied thoroughly, leading to weak inhibition only in very closely-spaced devices. This work approaches these problems by modeling current- and field- driven DW motion in a pair of adjacent DW-MTJ neurons. We maximize the magnitude of lateral inhibition by tuning the magnetic interaction between the neurons. The results are explained by current-driven DW velocity characteristics in response to an external magnetic field and quantified by an analytical model. Dependence of lateral inhibition strength on device parameters is also studied. Finally, lateral inhibition behavior in an array of 1000 DW-MTJ neurons is demonstrated. Our results provide a guideline for the optimization of lateral inhibition implementation in DW-MTJ neurons. With strong lateral inhibition achieved, a path towards competitive learning algorithms such as the winner-take-all are made possible on such neuromorphic devices.

All-Optical Electrophysiology Reveals the Role of Lateral Inhibition in Sensory Processing in Cortical Layer 1

Cortical layer 1 (L1) interneurons have been proposed as a hub for attentional modulation of underlying cortex, but the transformations that this circuit implements are not known. We combined genetically targeted voltage imaging with optogenetic activation and silencing to study the mechanisms underlying sensory processing in mouse barrel cortex L1. Whisker stimuli evoked precisely timed single spikes in L1 interneurons, followed by strong lateral inhibition. A mild aversive stimulus activated cholinergic inputs and evoked a bimodal distribution of spiking responses in L1. A simple conductance-based model that only contained lateral inhibition within L1 recapitulated the sensory responses and the winner-takes-all cholinergic responses, and the model correctly predicted that the network would function as a spatial and temporal high-pass filter for excitatory inputs. Our results demonstrate that all-optical electrophysiology can reveal basic principles of neural circuit function invivo and suggest an intuitive picture for how L1 transforms sensory and modulatory inputs. VIDEO ABSTRACT.

Strong, weak and neuron type dependent lateral inhibition in the olfactory bulb

In many sensory systems, different sensory features are transmitted in parallel by several different types of output neurons. In the mouse olfactory bulb, there are only two output neuron types, the mitral and tufted cells (M/T), which receive similar odor inputs, but they are believed to transmit different odor characteristics. How these two neuron types deliver different odor information is unclear. Here, by combining electrophysiology and optogenetics, it is shown that distinct inhibitory networks modulate M/T cell responses differently. Overall strong lateral inhibition was scarce, with most neurons receiving lateral inhibition from a handful of unorganized surrounding glomeruli (~5% on average). However, there was a considerable variability between different neuron types in the strength and frequency of lateral inhibition. Strong lateral inhibition was mostly found in neurons locked to the first half of the respiration cycle. In contrast, weak inhibition arriving from many surrounding glomeruli was relatively more common in neurons locked to the late phase of the respiration cycle. Proximal neurons could receive different levels of inhibition. These results suggest that there is considerable diversity in the way M/T cells process odors so that even neurons that receive the same odor input transmit different odor information to the cortex.

Optogenetic Modulation of a Minor Fraction of Parvalbumin-Positive Interneurons Specifically Affects Spatiotemporal Dynamics of Spontaneous and Sensory-Evoked Activity in Mouse Somatosensory Cortex in Vivo.

Parvalbumin (PV) positive interneurons exert strong effects on the neocortical excitatory network, but it remains unclear how they impact the spatiotemporal dynamics of sensory processing in the somatosensory cortex. Here, we characterized the effects of optogenetic inhibition and activation of PV interneurons on spontaneous and sensory-evoked activity in mouse barrel cortex in vivo. Inhibiting PV interneurons led to a broad-spectrum power increase both in spontaneous and sensory-evoked activity. Whisker-evoked responses were significantly increased within 20 ms after stimulus onset during inhibition of PV interneurons, demonstrating high temporal precision of PV-shaped inhibition. Multiunit activity was strongly enhanced in neighboring cortical columns, but not at the site of transduction, supporting a central and highly specific role of PV interneurons in lateral inhibition. Inversely, activating PV interneurons drastically decreased spontaneous and whisker-evoked activity in the principal column and exerted strong lateral inhibition. Histological assessment of transduced cells combined with quantitative modeling of light distribution and spike sorting revealed that only a minor fraction (~10%) of the local PV population comprising no more than a few hundred neurons is optogenetically modulated, mediating the observed prominent and widespread effects on neocortical processing.

Self-organized Notch dynamics generate stereotyped sensory organ patterns in Drosophila

INTRODUCTION: Spatial patterning in developing multicellular organisms relies on positional cues and cell-cell interactions. Stereotyped sensory organ arrangements in Drosophila are commonly attributed to a prepattern that defines regions of neural competence. Notch-mediated interactions then isolate sensory organ precursor (SOP) cells from among the competent cells. In support of this view, prepattern factors direct the expression of proneural factors in discrete clusters and determine the location of large bristles on the dorsal thorax. However, no such prepattern is known to establish the proneural stripes that give rise to finer-bristle rows. RATIONALE: By analogy with reaction-diffusion systems, we wondered whether Notch-mediated cell-cell interactions might organize a pattern of proneural stripes. To explore a possible role for Notch in proneural patterning, we generated fluorescent reporters for the proneural factors Achaete and Scute, the ligand Delta, and the Notch early-response factor E(spl)m3-HLH, which antagonizes proneural activity. We observed expression of these reporters in live and fixed samples throughout early pupal development. In parallel, we developed a mathematical model for Notch-mediated patterning. In this abstract model, the dynamics of a cell is expressed in terms of just two variables, for the state of the cell and the level of signal it receives. The model incorporates a series of plausible assumptions that govern its patterning behavior: Cells, which adopt the SOP fate in the absence of signal and the alternative, epidermal fate under high enough signal, exhibit a bistable response under intermediate signal levels. Inhibitory signaling from a cell varies nonlinearly with cell state and reaches beyond immediate neighbors. RESULTS: Before the onset of proneural gene expression, a bimodal gradient of Delta expression drove Notch activity; as a result of cis-inhibition, Notch was activated only in regions of intermediate Delta levels. This defined an inhibitory template for a first series of three proneural stripes. The spatial pattern of Notch activity dynamically changed as these first proneural stripes emerged, forming a negative template for a second group of intercalating stripes. Eventually, each stripe resolved into a row of isolated SOPs through Notch signaling. Thus, Notch mediated both proneural stripe patterning and SOP selection via a self-organized process. Simulations of the model, with a time-dependent inhibitory gradient describing the proneural-independent signaling seen in vivo, recapitulated the sequential emergence and resolution of proneural stripes. In both model and experiments, mutual inhibition drove a gradual refinement of the proneural group, concomitant with the buildup of proneural activity. Cells on the sides of the stripes were excluded first, such that stripes narrowed before isolated SOPs emerged. In terms of the model, cell-intrinsic bistability allowed cells with higher proneural activity, at the center of the stripes, to evade levels of inhibition that were sufficient to exclude cells on the sides. Nonlinear signaling allowed a smooth transition from weak mutual inhibition within an extended proneural group to strong lateral inhibition from emerging SOPs, ensuring that attrition of the proneural group proceeds until only isolated cells remain. Finally, the model correctly predicted the outcome of perturbation experiments affecting the pattern of Notch activity, the level and activity of Delta, and the range of signaling. CONCLUSION:Our results show that self-organized Notch signaling can establish stripe and dot patterns on a tissue-wide scale. A transient spatial bias, mediated by an initial gradient of Delta, is transduced by cell-cell interactions to produce a finer pattern of proneural stripes and bristle rows. Input from extrinsic positional cues and self-organization, sometimes considered competing paradigms for fate patterning, combine during bristle development and operate through the same signal. Self-organized Notch dynamics may provide a flexible substrate to generate diverse patterns in response to varying inputs.

Propagating wave segment under global feedback

In this study, we consider a propagating wave segment in two dimensions. A reaction diffusion system with global feedback is proposed, and spiral waves and propagating wave segments are shown. Propagating wave segments with large arc lengths can exist due to the absence of strong lateral inhibition. In order to study the properties of propagating wave segments, we propose a kinematic model with global feedback. When the elongating and shortening effects on the curve are balanced, stable propagating wave segments exist. For other cases, the initial wave segment evolves into a spiral wave or expanding wave or shrinking wave. The conditions for the propagating wave segment and the dependences of the solutions on the various relevant parameters are discussed.

The most numerous ganglion cell type of the mouse retina is a selective feature detector

The retina reports the visual scene to the brain through many parallel channels, each carried by a distinct population of retinal ganglion cells. Among these, the population with the smallest and densest receptive fields encodes the neural image with highest resolution. In human retina, and those of cat and macaque, these high-resolution ganglion cells act as generic pixel encoders: They serve to represent many different visual inputs and convey a neural image of the scene downstream for further processing. Here we identify and analyze high-resolution ganglion cells in the mouse retina, using a transgenic line in which these cells, called "W3", are labeled fluorescently. Counter to the expectation, these ganglion cells do not participate in encoding generic visual scenes, but remain silent during most common visual stimuli. A detailed study of their response properties showed that W3 cells pool rectified excitation from both On and Off bipolar cells, which makes them sensitive to local motion. However, they also receive unusually strong lateral inhibition, both pre- and postsynaptically, triggered by distant motion. As a result, the W3 cell can detect small moving objects down to the receptive field size of bipolar cells, but only if the background is featureless or stationary--an unusual condition. A survey of naturalistic stimuli shows that W3 cells may serve as alarm neurons for overhead predators.

Cortically activated interneurons shape spatial aspects of cortico-accumbens processing.

Basal ganglia circuits are organized as parallel loops that have been proposed to compete in a winner-take-all fashion to determine the appropriate behavioral outcome. However, limited experimental support for strong lateral inhibition mechanisms within striatal regions questions this model. Here, stimulation of the prefrontal cortex (PFC) using naturally occurring bursty patterns inhibited firing in most nucleus accumbens (NA) projection neurons. When an excitatory response was observed for one stimulation site, neighboring PFC sites evoked inhibition in the same neuron. Furthermore, PFC stimulation activated interneurons, and PFC-evoked inhibition was blocked by GABA(A) antagonists in corticoaccumbens slice preparations. Thus bursting PFC activity recruits local inhibition in the NA, shaping responses of projection neurons with a topographical arrangement that allows inhibition among parallel corticoaccumbens channels. The data indicate a high order of information processing within striatal circuits that should be considered in models of basal ganglia function and disease.

Reorganization of the auditory cortex specialized for echo-delay processing in the mustached bat.

Focal excess sensory stimulation evokes reorganization of a sensory system. It is usually an expansion of the neural representation of that stimulus resulting from the shifts of the tuning curves (receptive fields) of neurons toward those of the stimulated neurons. The auditory cortex of the mustached bat has an area that is highly specialized for the processing of target-distance information carried by echo delays. In this area, however, reorganization is due to shifts of the delay-tuning curves of neurons away from those of the stimulated cortical neurons. Elimination of inhibition in the target-distance processing area in the auditory cortex by a drug reverses the direction of the shifts in neural tuning curves. Therefore, such unique reorganization in the time domain is due to strong lateral inhibition in the highly specialized area of the auditory cortex.

How Simple Cells Are Made in a Nonlinear Network Model of the Visual Cortex

Simple cells in the striate cortex respond to visual stimuli in an approximately linear manner, although the LGN input to the striate cortex, and the cortical network itself, are highly nonlinear. Although simple cells are vital for visual perception, there has been no satisfactory explanation of how they are produced in the cortex. To examine this question, we have developed a large-scale neuronal network model of layer 4Calpha in V1 of the macaque cortex that is based on, and constrained by, realistic cortical anatomy and physiology. This paper has two aims: (1) to show that neurons in the model respond like simple cells. (2) To identify how the model generates this linearized response in a nonlinear network. Each neuron in the model receives nonlinear excitation from the lateral geniculate nucleus (LGN). The cells of the model receive strong (nonlinear) lateral inhibition from other neurons in the model cortex. Mathematical analysis of the dependence of membrane potential on synaptic conductances, and computer simulations, reveal that the nonlinearity of corticocortical inhibition cancels the nonlinear excitatory input from the LGN. This interaction produces linearized responses that agree with both extracellular and intracellular measurements. The model correctly accounts for experimental results about the time course of simple cell responses and also generates testable predictions about variation in linearity with position in the cortex, and the effect on the linearity of signal summation, caused by unbalancing the relative strengths of excitation and inhibition pharmacologically or with extrinsic current.

Neuronal responses in cat primary auditory cortex to natural and altered species-specific calls

We investigated how natural and morphed cat vocalizations are represented in primary auditory cortex (AI). About 40% of the neurons showed time-locked responses to major peaks in the vocalization envelope, 60% only responded at the onset. Simultaneously recorded multi-unit (MU) activity of these peak-tracking neurons on separate electrodes was significantly more synchronous during stimulation than under silence. Thus, the representation of the vocalizations is likely synchronously distributed across the cortex. The sum of the responses to the low and high frequency part of the meow, with the boundary at 2.5 kHz, was larger than the neuronal response to the natural meow itself, suggesting that strong lateral inhibition is shaping the response to the natural meow. In this sense, the neurons are combination-sensitive. The frequency-tuning properties and the response to amplitude-modulated tones of the MU recordings can explain the responses to natural, and temporally and spectrally altered vocalizations. Analysis of the mutual information in the firing rate suggests that the activity of at least 95 recording sites in AI would be needed to reliably distinguish between the nine different vocalizations. This suggests that a distributed representation based on temporal stimulus aspects may be more efficient than one based on firing rate.

Three modes of spatiotemporal preprocessing by eyes

1. Optimal spatiotemporal filters for early vision were computed as a function of signal-to-noise ratio (SNR) and alpha, a parameter defined as the ratio of the width of the probability distribution of velocities as perceived by the naturally behaving animal, and the characteristic velocity of the photoreceptors (the velocity required to move across a receptor's receptive field in a receptor's integration time). Animals that move slowly, on average, compared with the characteristic velocity of their photoreceptors have alpha << 1, animals that move fast have alpha >> 1. 2. For alpha << 1, the temporal part of the optimal filter adapts more to different SNRs (light levels) than the spatial part, leading to large adjustments in temporal resolving power and strong self-inhibition at high SNR, but little lateral inhibition. 3. For alpha >> 1, the spatial part of the filter adapts more strongly than the temporal part, leading to strong lateral inhibition at high SNR, and little self-inhibition. 4. For alpha approximately 1, both spatial and temporal properties change about equally much when varying SNR. 5. Varying the width of the angular sensitivity of the photoreceptors shows that for every combination of alpha and SNR there is an optimal width. Visual systems with large alpha need wider angular sensitivities, in particular at low SNR, in order to reach the information maximum than visual systems with small alpha.

Neuronal response properties within subregions of raccoon somatosensory cortex 1 week after digit amputation.

Multiple penetrations in the somatosensory cortex of three anesthetized raccoons 1 week following amputation of the fourth digit provided detailed information about somatotopy and neuronal responsiveness in the deafferented cortex. Recordings in a total of 601 penetrations (292 in deafferented cortex and 309 in the surrounding cortex) were compared with those from intact control animals described previously (Rasmusson et al., 1991). The level of spontaneous activity increased within the deafferented cortex, with 42% of the sites having high or moderate levels of spontaneous activity, in comparison with 18% in control animals. There was also an increase in the incidence of inhibitory responses to stimulation of adjacent digits (26% of the penetrations vs. 10% in control animals), confirming previous findings. These two variables, increased spontaneous activity and the presence of strong lateral inhibition, were highly correlated in individual penetrations. An unexpected finding was that the cortex representing the intact parts of forepaw was also disrupted with respect to these two measures, suggesting that amputation had an effect outside the deafferented region. In contrast, response properties that are more clearly a reflection of information processing in the dorsal column-medial lemniscal pathway (adaptation and threshold) were altered only within the deafferented region. The deafferented region was not homogeneous immediately after amputation, but consisted of a radically affected core region and a slightly affected fringe adjacent to the intact representations. This inhomogeneity had also been apparent with partial digit deafferentation, reported previously. The fringe, approximately 1 mm in width, may reflect overlapping projections from adjacent digits at one or more levels of the somatosensory pathway. Since the size of the fringe is similar to the maximum extent of reorganization found in other models of reorganization, the mechanisms of plasticity within this region may involve an unmasking of pre-existing synapses with slight modification in synaptic strength. However, the plasticity within the core region of the raccoon seen in these experiments, which may be 5 mm from nondeafferented cortex, requires more extensive changes, perhaps via polysynaptic pathways.

Lateral inhibition shapes the oscillatory responses of the horseshoe crab's compound eye

The synchronized response of the compound eye of the horseshoe crab to uniform illumination arises from the integration of excitation with the strong lateral inhibition present in many specimens. At the higher levels of excitation, the steady production of nerve impulses by individual eccentric cells is often replaced by periodically recurring volleys of impulses. This behavior is shown here to be the result of the temporal behavior of the post-synaptic potentials responsible for lateral inhibition. For a broad class of inhibitory potentials, a simple condition is established which separates potentials which permit volleys at high excitation levels from those which support only the steady production of impulses throughout the physiological range of excitations.

Synchronization of impulse generation by lateral inhibition in theLimulus compound eye

Under uniform illumination the optic nerve discharge from the lateral compound eye ofLimulus polyphemus can become oscillatory. This synchronization of eccentric cell impulse generation requires strong lateral inhibition (Barlow and Fraioli 1978). The simultaneous intra- and extracellular observations of eccentric cell responses described here allow examination of the process of synchronization. They also permit measurements of the phase relationship between the oscillatory hyperpolarization of the eccentrical cell membrane potential and the periodic bursts of optic nerve activity which cause the hyperpolarization through the lateral inhibitory network of the eye. On the basis of these observations, the following conclusions can be drawn.

On the theory of synchronization of lateral optic-nerve responses in Limulus. I. uniform excitation of the homogeneous retina

Published periodic solutions of a nonlinear integral equation arising in a theory of the response of the lateral compound eye of Limulus to light describe quantitatively the oscillatory responses of the lateral optic nerve to steady diffuse illumination, which have been observed in the eye in situ. More generally, the theory yields a system of nonlinear integral equations whose solutions describe the responses of each optic-nerve fiber originating in an illuminated region R of the eye. Numerical solutions of the system of equations for the case of uniform steady excitation by light, which are presented here, yield the following conclusions: In retinas having strong inhibitory interactions, the system of equations possesses periodic solutions which are synchronous across R. Calculations of the period employing recently published measurements of the time dependence of inhibition yield a value which agrees well with reported periods of the observed oscillatory response. Furthermore, strong lateral inhibition brings the solutions of the initial-value problem for the system of equations into synchrony rapidly. Synchrony and periodicity also appear in the long-time behavior of responses generated from spatially nonuniform initial conditions, which suggests that the observed oscillatory behavior should arise regardless of the manner in which the excitation of the region reaches its final steady level.

On the theory of synchronization of lateral optic-nerve responses in Limulus. II. nonuniform excitation and inhomogenous inhibition

The theory of synchronization of optic-nerve responses in the retina of Limulus, which was discussed in the preceding paper [1], is here applied to retinas in which either the lateral inhibitory interactions between ommatidia or the excitations of ommatidia by light exhibit random spatial variations. Numerical calculations show that in either case strong lateral inhibition can support a synchronous periodic response to uniform illumination similar to that found in [1]. The maximum strength of lateral inhibition required for such a response to occur depends only weakly on the degree of randomness of the inhibitory interactions, but it increases rapidly with increasingly random excitations. When the synchronous response exists, its period is equal to that calculated in [1] for an “ideal” retina in which the excitation by uniform illumination is uniform and lateral inhibition is spatially homogeneous.