Neurons In Lateral Geniculate Nucleus Research Articles

Degeneration of axotomized projection neurons in the rat dLGN: temporal progression of events and their mitigation by a single administration of FGF2.

Removal of visual cortex in the rat axotomizes projection neurons in the dorsal lateral geniculate nucleus (dLGN), leading to cytological and structural changes and apoptosis. Biotinylated dextran amine was injected into the visual cortex to label dLGN projection neurons retrogradely prior to removing the cortex in order to quantify the changes in the dendritic morphology of these neurons that precede cell death. At 12 hours after axotomy we observed a loss of appendages and the formation of varicosities in the dendrites of projection neurons. During the next 7 days, the total number of dendrites and the cross-sectional areas of the dendritic arbors of projection neurons declined to about 40% and 20% of normal, respectively. The response of dLGN projection neurons to axotomy was asynchronous, but the sequence of structural changes in individual neurons was similar; namely, disruption of dendrites began within hours followed by cell soma atrophy and nuclear condensation that commenced after the loss of secondary dendrites had occurred. However, a single administration of fibroblast growth factor-2 (FGF2), which mitigates injury-induced neuronal cell death in the dLGN when given at the time of axotomy, markedly reduced the dendritic degeneration of projection neurons. At 3 and 7 days after axotomy the number of surviving dendrites of dLGN projection neurons in FGF-2 treated rats was approximately 50% greater than in untreated rats, and the cross-sectional areas of dendritic arbors were approximately 60% and 50% larger. Caspase-3 activity in axotomized dLGN projection neurons was determined by immunostaining for fractin (fractin-IR), an actin cleavage product produced exclusively by activated caspase-3. Fractin-IR was seen in some dLGN projection neurons at 36 hours survival, and it increased slightly by 3 days. A marked increase in reactivity was seen by 7 days, with the entire dLGN filled with dense fractin-IR in neuronal cell somas and dendrites.

Activity-Dependent Regulation of Retinogeniculate Signaling by Metabotropic Glutamate Receptors

Thalamocortical neurons in dorsal lateral geniculate nucleus (dLGN) dynamically convey visual information from retina to the neocortex. Activation of metabotropic glutamate receptors (mGluRs) exerts multiple effects on neural integration in dLGN; however, their direct influence on the primary sensory input, namely retinogeniculate afferents, is unknown. In the present study, we found that pharmacological or synaptic activation of type 1 mGluRs (mGluR(1)s) significantly depresses glutamatergic retinogeniculate excitation in rat thalamocortical neurons. Pharmacological activation of mGluR(1)s attenuates excitatory synaptic responses in thalamocortical neurons at a magnitude sufficient to decrease suprathreshold output of these neurons. The reduction in both NMDA and AMPA receptor-dependent synaptic responses results from a presynaptic reduction in glutamate release from retinogeniculate terminals. The suppression of retinogeniculate synaptic transmission and dampening of thalamocortical output was mimicked by tetanic activation of retinogeniculate afferent in a frequency-dependent manner that activated mGluR(1)s. Retinogeniculate excitatory synaptic transmission was also suppressed by the glutamate transport blocker TBOA (dl-threo-β-benzyloxyaspartic acid), suggesting that mGluR(1)s were activated by glutamate spillover. The data indicate that presynaptic mGluR(1) contributes to an activity-dependent mechanism that regulates retinogeniculate excitation and therefore plays a significant role in the thalamic gating of visual information.

Relationship between orientation sensitivity and spatiotemporal receptive field structures of neurons in the cat lateral geniculate nucleus

Although it is thought that orientation selectivity first emerges in the primary visual cortex, several studies have reported that neurons in the cat lateral geniculate nucleus (LGN) are sensitive to stimulus orientation, especially for high spatial frequency (SF) stimuli. To understand how this orientation sensitivity emerges, we investigated the spatiotemporal structures of linear receptive fields (RFs) of LGN neurons. Orientation tunings at several SFs were measured using sinusoidal drifting grating stimuli. Fine spatiotemporal structures of the linear RFs were measured using a reverse correlation technique and two-dimensional dynamic Gaussian white noise stimuli. A non-linear response modulation function was estimated by comparing measured responses with responses predicted from a linear RF structure. Although we found that a population of LGN neurons exhibited significantly elongated linear RF centers and that the angles of the long axes corresponded well to the preferred orientations, the orientation tunings predicted from the linear RFs were significantly broader than those measured. These results suggest that orientation-tuned non-linear response modulation induced by stimulation outside the classical RF contributes to the sharp orientation tuning seen in LGN neurons.

Integrate-and-fire vs Poisson models of LGN input to V1 cortex: noisier inputs reduce orientation selectivity.

One of the reasons the visual cortex has attracted the interest of computational neuroscience is that it has well-defined inputs. The lateral geniculate nucleus (LGN) of the thalamus is the source of visual signals to the primary visual cortex (V1). Most large-scale cortical network models approximate the spike trains of LGN neurons as simple Poisson point processes. However, many studies have shown that neurons in the early visual pathway are capable of spiking with high temporal precision and their discharges are not Poisson-like. To gain an understanding of how response variability in the LGN influences the behavior of V1, we study response properties of model V1 neurons that receive purely feedforward inputs from LGN cells modeled either as noisy leaky integrate-and-fire (NLIF) neurons or as inhomogeneous Poisson processes. We first demonstrate that the NLIF model is capable of reproducing many experimentally observed statistical properties of LGN neurons. Then we show that a V1 model in which the LGN input to a V1 neuron is modeled as a group of NLIF neurons produces higher orientation selectivity than the one with Poisson LGN input. The second result implies that statistical characteristics of LGN spike trains are important for V1's function. We conclude that physiologically motivated models of V1 need to include more realistic LGN spike trains that are less noisy than inhomogeneous Poisson processes.

Feedforward Origins of Response Variability Underlying Contrast Invariant Orientation Tuning in Cat Visual Cortex

Contrast invariant orientation tuning in simple cells of the visual cortex depends critically on contrast dependent trial-to-trial variability in their membrane potential responses. This observation raises the question of whether this variability originates from within the cortical circuit or the feedforward inputs from the lateral geniculate nucleus (LGN). To distinguish between these two sources of variability, we first measured membrane potential responses while inactivating the surrounding cortex, and found that response variability was nearly unaffected. We then studied variability in the LGN, including contrast dependence, and the trial-to-trial correlation in responses between nearby neurons. Variability decreased significantly with contrast, whereas correlation changed little. When these experimentally measured parameters of variability were applied to a feedforward model of simple cells that included realistic mechanisms of synaptic integration, contrast-dependent, orientation independent variability emerged in the membrane potential responses. Analogous mechanisms might contribute to the stimulus dependence and propagation of variability throughout the neocortex.

Active Vision: Fixational Eye Movements Help Seeing Space in Time

The significance of the miniature eye movements that we make during visual fixation has been intensely debated for the last 80 years. Recent studies have revealed that these motions of the eyes fulfill an important functional role: helping to extract useful information from natural scenes.

Temporal Encoding of Spatial Information during Active Visual Fixation

Humans and other species continually perform microscopic eye movements, even when attending to a single point. These movements, which include drifts and microsaccades, are under oculomotor control, elicit strong neural responses, and have been thought to serve important functions. The influence of these fixational eye movements on the acquisition and neural processing of visual information remains unclear. Here, we show that during viewing of natural scenes, microscopic eye movements carry out a crucial information-processing step: they remove predictable correlations in natural scenes by equalizing the spatial power of the retinal image within the frequency range of ganglion cells' peak sensitivity. This transformation, which had been attributed to center-surround receptive field organization, occurs prior to any neural processing and reveals a form of matching between the statistics of natural images and those of normal eye movements. We further show that the combined effect of microscopic eye movements and retinal receptive field organization is to convert spatial luminance discontinuities into synchronous firing events, beginning the process of edge detection. Thus, microscopic eye movements are fundamental to two goals of early visual processing: redundancy reduction and feature extraction.

Development of orientation tuning in simple cells of primary visual cortex

Orientation selectivity and its development are basic features of visual cortex. The original model of orientation selectivity proposes that elongated simple cell receptive fields are constructed from convergent input of an array of lateral geniculate nucleus neurons. However, orientation selectivity of simple cells in the visual cortex is generally greater than the linear contributions based on projections from spatial receptive field profiles. This implies that additional selectivity may arise from intracortical mechanisms. The hierarchical processing idea implies mainly linear connections, whereas cortical contributions are generally considered to be nonlinear. We have explored development of orientation selectivity in visual cortex with a focus on linear and nonlinear factors in a population of anesthetized 4-wk postnatal kittens and adult cats. Linear contributions are estimated from receptive field maps by which orientation tuning curves are generated and bandwidth is quantified. Nonlinear components are estimated as the magnitude of the power function relationship between responses measured from drifting sinusoidal gratings and those predicted from the spatial receptive field. Measured bandwidths for kittens are slightly larger than those in adults, whereas predicted bandwidths are substantially broader. These results suggest that relatively strong nonlinearities in early postnatal stages are substantially involved in the development of orientation tuning in visual cortex.

Spatial distributions of cone inputs to cells of the parvocellular pathway investigated with cone-isolating gratings.

Receptive fields of midget ganglion cells and parvocellular lateral geniculate nucleus (LGN) neurons show color-opponent responses because they receive antagonistic input from the middle- and long-wavelength sensitive cones. It has been controversial as to whether this opponency can derive from random connectivity; if receptive field centers of cells near the fovea are cone-specific due to midget morphology, this would confer some degree of color opponency even with random cone input to the surround. A simple test of this mixed surround hypothesis is to compare spatial frequency tuning curves for luminance gratings and gratings isolating cone input to the receptive field center. If tuning curves for luminance gratings were bandpass, then with the mixed surround hypothesis tuning curves for gratings isolating the receptive field center cone class should also be bandpass, but to a lesser extent than for luminance. Tuning curves for luminance, chromatic, and cone-isolating gratings were measured in macaque retinal ganglion cells and LGN cells. We defined and measured a bandpass index to compare luminance and center cone-isolating tuning curves. Midget retinal ganglion cells and parvocellular LGN cells had bandpass indices between 0.1 and 1 with luminance gratings, but the index was usually near 1 (meaning low-pass tuning) when the receptive field center cone class alone was modulated. This is strong evidence for a considerable degree of cone-specific input to the surround. A fraction of midget and parvocellular cells showed evidence of incomplete specificity. Fitting the data with receptive field models revealed considerable intercell variability, with indications in some cells of a more complex receptive structure than a simple difference of Gaussians model.

Contrast invariant feature selectivity in balanced random networks

Event Abstract Back to Event Contrast invariant feature selectivity in balanced random networks Sadra Sadeh1*, Stefano Cardanobile1 and Stefan Rotter1 1 Bernstein Center Freiburg & Faculty of Biology, University of Freiburg, Germany Neurons in the primary visual cortex (V1) of mammals are highly selective for the orientation of a light bar [1, 2, 3], while they receive afferent connections from neurons in lateral geniculate nucleus (LGN) which are themselves not selective. The emergence of this property in cortex has been subject of debate since decades, and served as a paradigm to unravel the key mechanisms of information processing in the brain. We investigate the problem from a network point of view, by focusing on random recurrent networks with no specific pattern of connectivity. By exploring a large-scale network model of spiking neurons through simulations and theoretical analysis, we show how a purely random network operating in the inhibition dominated regime contributes to feature selectivity. In particular, we demonstrate how tuning amplification can happen in these networks as a consequence of 'selective attenuation', a general mechanism which selectively suppresses the common mode. By systematically investigating the relevant parameter space, we pinpoint different regimes of orientation selectivity, which yields testable predictions for the biological cortex. The 'selective attenuation' mechanism also yields contrast invariance [4, 3] of feature selectivity, which ensures feature detection for a wide range of input scales. Therefore, we suggest that the basic mechanism of contrast invariance is a consequence of intracortical interactions, and neither a single cell property, nor a purely feedforward mechanism. We argue in favor of 'tuning amplification' as the key process of the recurrent processing stage, for which no specific structure is needed. This mechanism could, in principle, also work for other sensory features and other sensory modalities as well, since the neural hardware necessary to achieve it is readily available in the cortex. Acknowledgements Funding by the German Ministry of Education and Research (BCCN Freiburg, grant 01GQ0420 and BFNT Freiburg*Tubingen, grant 01GQ0830) is acknowledged.

Spatially distinct actions of metabotropic glutamate receptor activation in dorsal lateral geniculate nucleus

Thalamocortical neurons in the dorsal lateral geniculate nucleus (dLGN) dynamically communicate visual information from the retina to the neocortex, and this process can be modulated via activation of metabotropic glutamate receptors (mGluRs). Neurons within dLGN express different mGluR subtypes associated with distinct afferent synaptic pathways; however, the physiological function of this organization is unclear. We report that the activation of mGluR(5), which are located on presynaptic dendrites of local interneurons, increases GABA output that in turn produces an increased inhibitory activity on proximal but not distal dendrites of dLGN thalamocortical neurons. In contrast, mGluR(1) activation produces strong membrane depolarization in thalamocortical neurons regardless of distal or proximal dendritic locations. These findings provide physiological evidence that mGluR(1) appear to be distributed along the thalamocortical neuron dendrites, whereas mGluR(5)-dependent action occurs on the proximal dendrites/soma of thalamocortical neurons. The differential distribution and activation of mGluR subtypes on interneurons and thalamocortical neurons may serve to shape excitatory synaptic integration and thereby regulate information gating through the thalamus.

Getting Drowsy? Alert/Nonalert Transitions and Visual Thalamocortical Network Dynamics

The effects of different EEG brain states on spontaneous firing of cortical populations are not well understood. Such state shifts may occur frequently under natural conditions, and baseline firing patterns can impact neural coding (e.g., signal-to-noise ratios, sparseness of coding). Here, we examine the effects of spontaneous transitions from alert to nonalert awake EEG states in the rabbit visual cortex (5 s before and after the state-shifts). In layer 4, we examined putative spiny neurons and fast-spike GABAergic interneurons; in layer 5, we examined corticotectal neurons. We also examined the behavior of retinotopically aligned dorsal lateral geniculate nucleus (LGNd) neurons, usually recorded simultaneously with the above cortical populations. Despite markedly reduced firing and sharply increased bursting in the LGNd neurons following the transition to the nonalert state, little change occurred in the spiny neurons of layer 4. However, fast-spike neurons of layer 4 showed a paradoxical increase in firing rates as thalamic drive decreased in the nonalert state, even though some of these cells received potent monosynaptic input from the same LGNd neurons whose rates were reduced. The firing rates of corticotectal neurons of layer 5, similarly to spiny cells of layer 4, were not state-dependent, but these cells did become more bursty in the nonalert state, as did the fast-spike cells. These results show that spontaneous firing rates of midlayer spiny populations are remarkably conserved following the shift from alert to nonalert states, despite marked reductions in excitatory thalamic drive and increased activity in local fast-spike inhibitory interneurons.

Thalamic Burst Firing Propensity: A Comparison of the Dorsal Lateral Geniculate and Pulvinar Nuclei in the Tree Shrew

Relay neurons in dorsal thalamic nuclei can fire high-frequency bursts of action potentials that ride the crest of voltage-dependent transient (T-type) calcium currents [low-threshold spike (LTS)]. To explore potential nucleus-specific burst features, we compared the membrane properties of dorsal lateral geniculate nucleus (dLGN) and pulvinar nucleus relay neurons using in vitro whole-cell recording in juvenile and adult tree shrew (Tupaia) tissue slices. We injected current ramps of variable slope into neurons that were sufficiently hyperpolarized to de-inactivate T-type calcium channels. In a small percentage of juvenile pulvinar and dLGN neurons, an LTS could not be evoked. In the remaining juvenile neurons and in all adult dLGN neurons, a single LTS could be evoked by current ramps. However, in the adult pulvinar, current ramps evoked multiple LTSs in >70% of recorded neurons. Using immunohistochemistry, Western blot techniques, unbiased stereology, and confocal and electron microscopy, we found that pulvinar neurons expressed more T-type calcium channels (Ca(v) 3.2) and more small conductance potassium channels (SK2) than dLGN neurons and that the pulvinar nucleus contained a higher glia-to-neuron ratio than the dLGN. Hodgkin-Huxley-type compartmental models revealed that the distinct firing modes could be replicated by manipulating T-type calcium and SK2 channel density, distribution, and kinetics. The intrinsic properties of pulvinar neurons that promote burst firing in the adult may be relevant to the treatment of conditions that involve the adult onset of aberrant thalamocortical interactions.

Investigation of cytoskeleton proteins in neurons of the cat lateral geniculate nucleus

The gross structure of neurons is supported by proteins that compose the cytoskeleton. Neurofilaments are intermediate cytoskeletal proteins that contribute to neuron structure and function, and three neurofilament subunits different in their molecular mass assemble to form heteropolymers that produce a structure-providing intracellular scaffold. The light neurofilament subunit is obligatory and can assemble with either the medium or heavy subunit, indicating some degree of independence between subunits. The presence of the heavy subunit has been shown to be associated with mature cells and is linked to large neurons in the cerebral cortex and thalamus. Spectrin is a membrane-associated actin-binding protein that, like neurofilament, has been linked to neuron shape. In this study of the cat dorsal lateral geniculate nucleus (dLGN) we examined whether labeling for neurofilament subunits and spectrin is linked to neuron size. We found that about one-third of neurons contained a visible amount of labeling for each neurofilament subunit, and the bulk of these labeled cells were large in comparison to the general population of neurons. The distribution of neuron sizes was not different between neurofilament subunits, indicating that neurofilament subunit content is not determined by neuron size. Spectrin labeling was evident in most dLGN neurons, and was not related to the size of neurons. That reactivity for neurofilament was predominant in large cells led us to directly examine the relationship between neurofilament and interneurons. The large majority of neurofilament-positive neurons did not contain GABA, indicating that neurofilament is predominant in projection cells and not in interneurons.

Coarse-to-Fine Changes of Receptive Fields in Lateral Geniculate Nucleus Have a Transient and a Sustained Component That Depend on Distinct Mechanisms

Visual processing in the brain seems to provide fast but coarse information before information about fine details. Such dynamics occur also in single neurons at several levels of the visual system. In the dorsal lateral geniculate nucleus (LGN), neurons have a receptive field (RF) with antagonistic center-surround organization, and temporal changes in center-surround organization are generally assumed to be due to a time-lag of the surround activity relative to center activity. Spatial resolution may be measured as the inverse of center size, and in LGN neurons RF-center width changes during static stimulation with durations in the range of normal fixation periods (250–500 ms) between saccadic eye-movements. The RF-center is initially large, but rapidly shrinks during the first ∼100 ms to a rather sustained size. We studied such dynamics in anesthetized cats during presentation (250 ms) of static spots centered on the RF with main focus on the transition from the first transient and highly dynamic component to the second more sustained component. The results suggest that the two components depend on different neuronal mechanisms that operate in parallel and with partial temporal overlap rather than on a continuously changing center-surround balance. Results from mathematical modeling further supported this conclusion. We found that existing models for the spatiotemporal RF of LGN neurons failed to account for our experimental results. The modeling demonstrated that a new model, in which the response is given by a sum of an early transient component and a partially overlapping sustained component, adequately accounts for our experimental data.

Rapid Plasticity of Visual Responses in the Adult Lateral Geniculate Nucleus

Compared to the developing visual system, where neuronal plasticity has been well characterized at multiple levels, little is known about plasticity in the adult, particularly within subcortical structures. We made intraocular injections of 2-amino-4-phosphonobutyric acid (APB) in adult cats to block visual responses in On-center retinal ganglion cells and examined the consequences on visual responses in the lateral geniculate nucleus (LGN) of the thalamus. In contrast to current views of retinogeniculate organization, which hold that On-center LGN neurons should become silent with APB, we find that ∼50% of On-center neurons rapidly develop Off-center responses. The time course of these emergent responses and the actions of APB in the retina indicate the plasticity occurs within the LGN. These results suggest there is greater divergence of retinogeniculate connections than previously recognized and that functionally silent, nonspecific retinal inputs can serve as a substrate for rapid plasticity in the adult.

Local action for global vision

Local action for global vision

Contrast adaptation in cat lateral geniculate nucleus and influence of corticothalamic feedback

Contrast adaptation is a basic property of visual information processing. However, important questions about contrast adaptation in the lateral geniculate nucleus (LGN) remain. For example, it is unclear whether the different information channels have the same or distinct contrast adaptation properties and mechanisms. It has been recognized that the visual system is not a one-way ascending pathway, but also contains descending feedback projections. Although studies have explored the role of this feedback system, it is unclear whether corticothalamic feedback contributes to adaptation in the LGN. To investigate these questions, we studied contrast adaptation of LGN neurons in anesthetized and paralysed cats by measuring electrophysiological responses to visual test stimuli before and after adaptation induced by prolonged visual stimulation. After adaptation, contrast response functions were usually shifted towards higher contrasts, indicating decreased contrast gain, and the maximum response decreased. Also, contrast adaptation effects were stronger in Y-cells than in X-cells. Furthermore, adaptation effects were still observed in the LGN when the corticothalamic feedback was inactivated. Changes in the contrast gain of Y-cells were diminished in the absence of feedback, while contrast gain was largely unchanged in X-cells. Our observations confirm that contrast adaptation occurs in LGN neurons and furthermore demonstrate that Y-cells show stronger adaptation effects than X-cells. These results also provide an example of how corticothalamic feedback modulates contrast information processing distinctly in different information channels.

Cortical feedback regulation of input to visual cortex: role of intrageniculate interneurons

Neurons in the dorsal lateral geniculate nucleus (dLGN) process and transmit visual signals from retina to visual cortex. The processing is dynamically regulated by cortical excitatory feedback to neurons in dLGN, and synaptic short-term plasticity (STP) has an important role in this regulation. It is known that corticogeniculate synapses on thalamocortical (TC) projection-neurons are facilitating, but type and characteristics of STP of synapses on inhibitory interneurons in dLGN are unknown. We studied STP at corticogeniculate synapses on interneurons and compared the results with STP-characteristics of corticogeniculate synapses on TC neurons to gain insights into the dynamics of cortical regulation of processing in dLGN. We studied neurons in thalamic slices from glutamate decarboxylase 67 (GAD67)–green fluorescent protein (GFP) knock-in mice and made whole-cell recordings of responses evoked by electrical paired-pulse and pulse train stimulation of cortical afferents. We found that cortical excitations of interneurons and TC neurons have distinctly different properties. A single pulse evoked larger EPSCs in interneurons than in TC neurons. However, repetitive stimulation induced frequency-dependent depression of interneurons in contrast to the facilitation of TC neurons. Thus, through these differences of STP mechanisms, the balance of cortical excitation of the two types of neurons could change during stimulation from strongest excitation of interneurons to strongest excitation of TC neurons depending on stimulus frequency and duration, and thereby contribute to activity-dependent cortical regulation of thalamocortical transmission between net depression and net facilitation. Studies of postsynaptic response patterns of interneurons to train stimulation demonstrated that cortical input can activate different types of neuronal integration mechanisms that in addition to the STP mechanisms may change the output from dLGN. Lower stimulus intensity, presumably activating few cortical afferents, or moderate frequencies, elicited summation of graded EPSPs reflecting synaptic depression. However, strong activation through higher intensity or frequency, elicited complex response patterns in interneurons caused at least partly by activation of calcium conductances.

The impact of brief exposure to high contrast on the contrast response of neurons in primate lateral geniculate nucleus

Prolonged exposure to an effective stimulus generally reduces the sensitivity of neurons early in the visual pathway. Yet eye and head movements bring about frequent changes in the retinal image, and it is less clear that exposure to brief presentations will produce similar desensitization. To address this, we made extracellular recordings from single neurons in the lateral geniculate nucleus of anesthetized marmosets, a New World primate. We measured the contrast response for drifting gratings before and after 0.5-s exposure to a high-contrast drifting grating, a stationary grating, or a blank screen. Prior exposure to the drifting grating reduced the contrast sensitivity of cells in the magnocellular pathway, on average by 23%; this reduction remained strong when the adapting and test stimuli were separated by 0.4 s. Exposure to a stationary grating of the preferred spatial phase did not change the contrast response; exposure to the opposite spatial phase did. None of the brief adaptors reduced the sensitivity of parvocellular cells. We conclude that brief periods of high contrast, such as those that would be expected to occur during a normal visual fixation, are sufficient to reduce the sensitivity of magnocellular-pathway cells.