Lateral Geniculate Nucleus Relay Cells Research Articles

Dynamics of Temporal Integration in the Lateral Geniculate Nucleus.

Before visual information from the retina reaches primary visual cortex (V1), it is dynamically filtered by the lateral geniculate nucleus (LGN) of the thalamus, the first location within the visual hierarchy at which nonretinal structures can significantly influence visual processing. To explore the form and dynamics of geniculate filtering we used data from monosynpatically connected pairs of retinal ganglion cells (RGCs) and LGN relay cells in the cat that, under anesthetized conditions, were stimulated with binary white noise and/or drifting sine-wave gratings to train models of increasing complexity to predict which RGC spikes were relayed to cortex, what we call “relay status.” In addition, we analyze and compare a smaller dataset recorded in the awake state to assess how anesthesia might influence our results. Consistent with previous work, we find that the preceding retinal interspike interval (ISI) is the primary determinate of relay status with only modest contributions from longer patterns of retinal spikes. Including the prior activity of the LGN cell further improved model predictions, primarily by indicating epochs of geniculate burst activity in recordings made under anesthesia, and by allowing the model to capture gain control-like behavior within the awake LGN. Using the same modeling framework, we further demonstrate that the form of geniculate filtering changes according to the level of activity within the early visual circuit under certain stimulus conditions. This finding suggests a candidate mechanism by which a stimulus specific form of gain control may operate within the LGN.

Emergence of Orientation Selectivity in the Mammalian Visual Pathway

Orientation selectivity is a property of mammalian primary visual cortex (V1) neurons, yet its emergence along the visual pathway varies across species. In carnivores and primates, elongated receptive fields first appear in V1, whereas in lagomorphs such receptive fields emerge earlier, in the retina. Here we examine the mouse visual pathway and reveal the existence of orientation selectivity in lateral geniculate nucleus (LGN) relay cells. Cortical inactivation does not reduce this orientation selectivity, indicating that cortical feedback is not its source. Orientation selectivity is similar for LGN relay cells spiking and subthreshold input to V1 neurons, suggesting that cortical orientation selectivity is inherited from the LGN in mouse. In contrast, orientation selectivity of cat LGN relay cells is small relative to subthreshold inputs onto V1 simple cells. Together, these differences show that although orientation selectivity exists in visual neurons of both rodents and carnivores, its emergence along the visual pathway, and thus its underlying neuronal circuitry, is fundamentally different.

Firing-rate models capture essential response dynamics of LGN relay cells

Firing-rate models provide a practical tool for studying signal processing in the early visual system, permitting more thorough mathematical analysis than spike-based models. We show here that essential response properties of relay cells in the lateral geniculate nucleus (LGN) can be captured by surprisingly simple firing-rate models consisting of a low-pass filter and a nonlinear activation function. The starting point for our analysis are two spiking neuron models based on experimental data: a spike-response model fitted to data from macaque (Carandini et al. J. Vis., 20(14), 1-2011, 2007), and a model with conductance-based synapses and afterhyperpolarizing currents fitted to data from cat (Casti et al. J. Comput. Neurosci., 24(2), 235-252, 2008). We obtained the nonlinear activation function by stimulating the model neurons with stationary stochastic spike trains, while we characterized the linear filter by fitting a low-pass filter to responses to sinusoidally modulated stochastic spike trains. To account for the non-Poisson nature of retinal spike trains, we performed all analyses with spike trains with higher-order gamma statistics in addition to Poissonian spike trains. Interestingly, the properties of the low-pass filter depend only on the average input rate, but not on the modulation depth of sinusoidally modulated input. Thus, the response properties of our model are fully specified by just three parameters (low-frequency gain, cutoff frequency, and delay) for a given mean input rate and input regularity. This simple firing-rate model reproduces the response of spiking neurons to a step in input rate very well for Poissonian as well as for non-Poissonian input. We also found that the cutoff frequencies, and thus the filter time constants, of the rate-based model are unrelated to the membrane time constants of the underlying spiking models, in agreement with similar observations for simpler models.

Effects of cortical feedback on the spatial properties of relay cells in the lateral geniculate nucleus

Feedback connections to early-level sensory neurons have been shown to affect many characteristics of their neural response. Because selectivity for stimulus size is a fundamental property of visual neurons, we examined the summation tuning and discretely mapped receptive field (RF) properties of cells in the lateral geniculate nucleus (LGN) both with and without feedback from visual cortex. Using extracellular recording in halothane-anesthetized cats, we used small luminance probes displaced in Cartesian coordinates to measure discrete response area, and optimal sinusoidal gratings of varying diameter to estimate preferred optimal summation size and level of center-surround antagonism. In conditions where most cortical feedback was pharmacologically removed, discretely mapped RF response areas showed an overall significant enlargement for the population compared with control conditions. A switch to increased levels of burst firing, spatially displaced from the RF center, suggested this was mediated by changes in excitatory-inhibitory balance across visual space. With the use of coextensive stimulation, there were overall highly significant increases in the optimal summation size and reduction of surround antagonism with removal of cortical feedback in the LGN. When fitted with a difference-of-Gaussian (DOG) model, changes in the center size, center amplitude, and surround amplitude parameters were most significantly related to the removal of cortical feedback. In summary, corticothalamic innervation of the visual thalamus can modify spatial summation properties in LGN relay cells, an effect most parsimoniously explained by changes in the excitatory-inhibitory balance.

A minimal mechanistic model for temporal signal processing in the lateral geniculate nucleus.

The receptive fields of cells in the lateral geniculate nucleus (LGN) are shaped by their diverse set of impinging inputs: feedforward synaptic inputs stemming from retina, and feedback inputs stemming from the visual cortex and the thalamic reticular nucleus. To probe the possible roles of these feedforward and feedback inputs in shaping the temporal receptive-field structure of LGN relay cells, we here present and investigate a minimal mechanistic firing-rate model tailored to elucidate their disparate features. The model for LGN relay ON cells includes feedforward excitation and inhibition (via interneurons) from retinal ON cells and excitatory and inhibitory (via thalamic reticular nucleus cells and interneurons) feedback from cortical ON and OFF cells. From a general firing-rate model formulated in terms of Volterra integral equations, we derive a single delay differential equation with absolute delay governing the dynamics of the system. A freely available and easy-to-use GUI-based MATLAB version of this minimal mechanistic LGN circuit model is provided. We particularly investigate the LGN relay-cell impulse response and find through thorough explorations of the model's parameter space that both purely feedforward models and feedback models with feedforward excitation only, can account quantitatively for previously reported experimental results. We find, however, that the purely feedforward model predicts two impulse response measures, the time to first peak and the biphasic index (measuring the relative weight of the rebound phase) to be anticorrelated. In contrast, the models with feedback predict different correlations between these two measures. This suggests an experimental test assessing the relative importance of feedforward and feedback connections in shaping the impulse response of LGN relay cells.

Molecular compartmentalization of lateral geniculate nucleus in the gray squirrel (Sciurus carolinensis)

Previous research has suggested that the three physiologically defined relay cell-types in mammalian lateral geniculate nucleus (LGN)—called parvocellular (P), magnocellular (M), and koniocellular (K) cells in primates and X, Y, and W cells in other mammals—each express a unique combination of cell-type marker proteins. However, some of the relationships among physiological classification and protein expression found in primates, prosimians, and tree shrews do not apply to carnivores and murid rodents. It remains unknown whether these are exceptions to a common rule for all mammals, or whether these relationships vary over a wide range of species. To address this question, we examined protein expression in the gray squirrel (Sciurus carolinensis), a highly visual rodent. Unlike many rodents, squirrel LGN is well laminated, and the organization of X-like, Y-like, and W-like cells relative to the LGN layers has been characterized physiologically. We labeled tissue sections through visual thalamus with antibodies to calbindin and parvalbumin, the antibody Cat-301, and the lectin WFA. Calbindin expression was found in W-like cells in LGN layer 3, just adjacent to the optic tract. These results suggest that calbindin is a common marker for the konicellular pathway in mammals. However, while parvalbumin expression characterizes P and M cells in primates and X and Y cells in tree shrews, here it identifies only about half of the X-like cells in LGN layers 1 and 2. Putative Y/M cell markers did not differentiate relay cells in this animal. Together, these results suggest that protein expression patterns among LGN relay cell classes are variable across mammals.

Extended difference-of-Gaussians model incorporating cortical feedback for relay cells in the lateral geniculate nucleus of cat.

A striking feature of the organization of the early visual pathway is the significant feedback from primary visual cortex to cells in the dorsal lateral geniculate nucleus (LGN). Despite numerous experimental and modeling studies, the functional role for this feedback remains elusive. We present a new firing-rate-based model for LGN relay cells in cat, explicitly accounting for thalamocortical loop effects. The established DOG model, here assumed to account for the spatial aspects of the feedforward processing of visual stimuli, is extended to incorporate the influence of thalamocortical loops including a full set of orientation-selective cortical cell populations. Assuming a phase-reversed push-pull arrangement of ON and OFF cortical feedback as seen experimentally, this extended DOG (eDOG) model exhibits linear firing properties despite non-linear firing characteristics of the corticothalamic cells. The spatiotemporal receptive field of the eDOG model has a simple algebraic structure in Fourier space, while the real-space receptive field, as well as responses to visual stimuli, are found by evaluation of an integral. As an example application we use the eDOG model to study effects of cortical feedback on responses to flashing circular spots and patch-grating stimuli and find that the eDOG model can qualitatively account for experimental findings.

Cortical modulation of neuronal activity in the cat's lateral geniculate and perigeniculate nuclei: a modeling study

The role of cortical feedback in thalamo-cortical processing loop have been extensively investigated over the last decades. In general, these studies focused on cortical feedback exerted over lateral geniculate nucleus (LGN) principal cells, only in several cases the effects of cortical inactivation were investigated simultaneously in both thalamic relay cells and perigeniculate nucleus (PGN) inhibitory neurons. In the previous study [1] we showed in the cat that cessation of cortical input by cooling of visual cortex (areas 17 and 18) decreased spontaneous activity of LGN relay cells and increased spontaneous activity of PGN neurons. In contrast, visually evoked responses of most PGN neurons and LGN principal cells both decreased. To identify network mechanisms underlying such functional changes we conducted a modelling study in NEURON on several networks of point neurons with varied model parameters, such as membrane properties, synaptic weights and axonal delays. We considered five network topologies of the retino-geniculo-cortical pathway [2-6]. All models were robust against changes of axonal delays except for delay between LGN feed-forward interneuron and principal cell when this connection was present. In all such cases the models were found to be very sensitive to this delay. To reproduce the experimental results [1] the models required: 1) reciprocally connected PGN cells, connection present only in two model variants [2,3], and 2) slow decay of intracellular calcium. We found model [2] most consistent with known physiology and anatomy of the cat. Table ​Table1.1. Figure ​Figure11. Table 1 Mean spontaneous activity (spikes/s) for tested models (mean of 30 repetitions) and t-test P values. Figure 1 The model network of the thalamo-cortical loop following [2]. The model in [3] does not include LGN feedforward interneuron. Both variants reproduced experimental results [1]. White circles – relay cells, black – inhibitory neurons.

Stimulus size dependence of information transfer from retina to thalamus

Relay cells in the mammalian lateral geniculate nucleus (LGN) are driven primarily by single retinal ganglion cells (RGCs). However, an LGN cell responds typically to less than half of the spikes it receives from the RGC that drives it, and without retinal drive the LGN is silent (Kaplan and Shapley, 1984). Recent studies, which used stimuli restricted to the receptive field (RF) center, show that despite the great loss of spikes, more than half of the information carried by the RGC discharge is typically preserved in the LGN discharge (Sincich et al., 2009), suggesting that the retinal spikes that are deleted by the LGN carry less information than those that are transmitted to the cortex. To determine how LGN relay neurons decide which retinal spikes to respond to, we recorded extracellularly from the cat LGN relay cell spikes together with the slow synaptic (‘S’) potentials that signal the firing of retinal spikes. We investigated the influence of the inhibitory surround of the LGN RF by stimulating the eyes with spots of various sizes, the largest of which covered the center and surround of the LGN relay cell's RF. We found that for stimuli that activated mostly the RF center, each LGN spike delivered more information than the retinal spike, but this difference was reduced as stimulus size increased to cover the RF surround. To evaluate the optimality of the LGN editing of retinal spikes, we created artificial spike trains from the retinal ones by various deletion schemes. We found that single LGN cells transmitted less information than an optimal detector could.

The Emergence of Contrast-Invariant Orientation Tuning in Simple Cells of Cat Visual Cortex

Simple cells in primary visual cortex exhibit contrast-invariant orientation tuning, in seeming contradiction to feed-forward models that rely on lateral geniculate nucleus (LGN) input alone. Contrast invariance has therefore been thought to depend on the presence of intracortical lateral inhibition. In vivo intracellular recordings instead suggest that contrast invariance can be explained by three properties of the excitatory pathway. (1) Depolarizations evoked by orthogonal stimuli are determined by the amount of excitation a cell receives from the LGN, relative to the excitation it receives from other cortical cells. (2) Depolarizations evoked by preferred stimuli saturate at lower contrasts than the spike output of LGN relay cells. (3) Visual stimuli evoke contrast-dependent changes in trial-to-trial variability, which lead to contrast-dependent changes in the relationship between membrane potential and spike rate. Thus, high-contrast, orthogonally oriented stimuli that evoke significant depolarizations evoke few spikes. Together these mechanisms, without lateral inhibition, can account for contrast-invariant stimulus selectivity.

Modulatory effects mediated by metabotropic glutamate receptor 5 on lateral geniculate nucleus relay cells

Glutamate is thought to be the excitatory neurotransmitter in the lateral geniculate nucleus (LGN) of the cat, mediating visual transmission from the retina via ionotropic receptors of both D,L-alpha-amino-3-hydroxy-5-alpha-methyl-4-isoxazolepropionate and N-methyl-D-aspartate subtypes. Moreover, glutamate also exerts an important modulatory influence on LGN cells, where metabotropic glutamate receptors (mGluRs) seem to play a crucial role. Here we show in anesthetized adult cats that iontophoretic application of the specific mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) produced two, distinctly different, effects on LGN neurons. Visual responses to flashing spots and drifting gratings were attenuated (decreased by an average of 59%) in 13 of 23 of the cells but augmented (increased by an average of 60%) in 10 of 23 of the cells. Further, in each case when the specific mGluR5 agonist (R,S)-2-chloro-5-hydroxyphenylglycine was applied, the effects obtained were the opposite to those of MPEP. Data obtained in a second group of experiments to determine a possible interaction between mGluR5 blockade by MPEP and glutamate ionotropic receptors show that, in the majority of neurons (11 of 15, 73%), the MPEP-mediated effects seem to be independent of N-methyl-D-aspartate and D,L-alpha-amino-3-hydroxy-5-alpha-methyl-4-isoxazolepropionate receptor activity. Our results demonstrate a physiological role for mGluR5 in controlling retinal input and show, in vivo, a more intricate scenario than previously suggested, highlighting the complexity of metabotropic receptor interactions with excitatory and inhibitory elements in the thalamus.

Dynamic properties of retino-geniculate synapses in the cat.

Simultaneous recordings from relay cells in the lateral geniculate nucleus (LGN) and their retinal afferents were used to examine the rules governing the transmission of spikes across the retino-geniculate synapse. Retinal spikes that terminate short retinal interspike intervals are much more likely to be transmitted across the synapse than spikes terminating longer intervals. This facilitation can be observed for interspike intervals as long as 50 ms when retinal firing rates are low, but the range of effective intervals decreases exponentially as retinal firing rate increases. Contribution, the fraction of LGN spikes triggered by an individual retinal afferent, is typically much higher during visual stimulation than during maintained activity, and these differences are unrelated to presynaptic or postsynaptic firing rate. It is suggested that this effect is a manifestation of increased synchronization of spikes among retinal afferents to the geniculate cell during structured visual stimulation, and that this synchronization offers a means of enhancing signal-to-noise ratio at the retino-geniculate synapse. Cross-correlograms between geniculate burst spikes and retinal afferents often contain two distinct peaks; a short latency peak that results from direct coupling between burst spikes and retinal input spikes, and a longer latency peak that represents indirect coupling in which retinal spikes trigger the calcium spike underlying the burst. Direct coupling is most likely to occur for the later spikes in the burst, and is present regardless of whether the calcium spike underlying the burst is triggered by the same or a different retinal afferent. These results further illuminate the relationship between tonic and burst modes of retino-geniculate transmission and indicate that bursts in LGN relay cells can be viewed as a mechanism of signal amplification, producing signals whose timing is potentially related to the temporal structure of a stimulus, independent of presynaptic and postsynaptic firing rate. This mechanism also appears to capitalize on the synchronization that is present among parallel retinal afferents to a geniculate cell.

Studies of physiology and the morphology of the cat LGN following proton irradiation

Purpose: We have examined the effects of proton irradiation on the histologic and receptive field properties of thalamic relay cells in the cat visual system. The cat lateral geniculate nucleus (LGN) is a large structure with well–defined anatomical boundaries, and well–described afferent, efferent, and receptive field properties. Methods and Materials: A 1.0-mm proton microbeam was used on the cat LGN to determine short-term (3 months) and long-term (9 months) receptive field effects of irradiation on LGN relay cells. The doses used were 16-, 40-, and 60-gray (Gy). Results: Following irradiation, abnormalities in receptive field organization were found in 40- and 60-Gy short-term animals, and in all of the long-term animals. The abnormalities included “silent” areas of the LGN where a visual response could not be evoked and other regions that had unusually large or small compound receptive fields. Histologic analysis failed to identify cellular necrosis or vascular damage in the irradiated LGN, but revealed a disruption in retinal afferents to areas of the LGN. Conclusions: These results indicate that microbeam proton irradiation can disrupt cellular function in the absence of obvious cellular necrosis. Moreover, the area and extent of this disruption increased with time, having larger affect with longer post-irradiation periods.

Rapid eye movement sleep deprivation in kittens amplifies LGN cell-size disparity induced by monocular deprivation

The abundance of rapid eye movement (REM) sleep in the neonatal mammal and its subsequent decline in the course of development, as well as the dramatic and widespread enhancement of CNS activity during REM sleep, led us to propose that this state plays a functional role in the normative physiological and structural maturation of the brain [54]. When, after 1 week of monocular deprivation (MD), a second week of MD was coupled with behavioral deprivation of REM sleep, the structural alteration in the visual system provoked by MD alone (interlaminar relay cell-size disparity in the lateral geniculate nucleus (LGN)) was amplified. With the addition of REM deprivation during MD, the LGN cells connected to the surgically patched eye, which are smaller than normal after MD, became even smaller, whereas the LGN cells receiving input from the seeing eye, which display compensatory hypertrophy after MD, grew even larger. We believe that the interlaminar disparity effect widened because during REM deprivation, the already vision-compromised LGN cells associated with the patched eye also lose the ascending brainstem activation reaching them during the REM state. Loss of the two main sources of ‘afference’ by these LGN cells permits their seeing-eye LGN counterparts to gain even greater advantage in the competition for synaptic connections in cortex, which is reflected in the relative soma sizes of the LGN relay cells. It is likely that the relatively abundant REM state in early maturation provides symmetric stimulation to all LGN relay cells, irrespective of eye of innervation. The symmetric activation propagated from brainstem to LGN acts to ‘buffer’ abnormal, asymmetric visual input and, thereby diminishes the extreme, asymmetric structural alteration that results from MD in the absence of REM sleep. We conclude that REM sleep-generated CNS discharge in development has the effect of ‘protecting’ the CNS against excessive plasticity changes. This is consistent with the possibility that REM sleep plays a role in the genetically programmed processes that direct normative brain development.

Dynamics of neurons in the cat lateral geniculate nucleus: in vivo electrophysiology and computational modeling.

1. We investigated the time domain transformation that thalamocortical relay cells of the cat lateral geniculate nucleus (LGN) perform on their retinal input, and used computational modeling to explore the biophysical properties that determine the dynamics of the LGN relay cells in vivo. 2. We recorded simultaneously the input (S potentials) and output (action potentials) of 50 cat LGN relay cells stimulated by drifting sinusoidal gratings of varying temporal frequency. The temporal modulation transfer functions (TMTFs) of the neurons were derived from these data. The burstiness of the LGN spike trains was also assessed using objective criteria. 3. We found that the form of the TMTF was quite variable among cells, ranging from low-pass to strongly band-pass. The optimal temporal frequency of band-pass neurons was between 2 and 8 Hz. In addition, the TMTF of some cells was nonstationary: their temporal tuning changed with time. 4. The temporal tuning of a cell was directly related to the degree of burstiness of its spike train. Tonically firing relay cells had low-pass TMTFs, whereas the most bursty neurons exhibited the most sharply band-pass transfer functions. This was also true for single cells that altered their temporal tuning: a shift to more band-pass tuning was associated with increased burstiness of the spike train, and vice versa. 5. We constructed a computer simulation of the LGN relay cell. The model was a simplified five-channel version of the thalamocortical neuron model of McCormick and Huguenard. It incorporated the quantitative kinetics of the Ca2+ T channel, as well as the Hodgkin-Huxley Na+ and K+ channels, as the only active membrane currents. To simulate the in vivo dynamics of the relay cell, the input to the model consisted of trains of synaptic potentials, recorded as S potentials in our physiological experiments. 6. When the resting membrane potential of the model neuron was relatively depolarized, the model's TMTF was low-pass, with no bursting evident in the simulated spike train. At hyperpolarized resting membrane potentials, however, the modeled TMTF was band-pass, with frequent burst discharges. Thus the biophysical model reproduced not only the range of dynamics seen in real LGN relay cells, but also the dependence of the overall dynamics on the burstiness of the spike train. However, neither of these phenomena could be simulated without the T channel. Thus the simulations demonstrated that the T-type Ca2+ channel was necessary and sufficient to explain the LGN dynamics observed in physiological experiments.(ABSTRACT TRUNCATED AT 400 WORDS)

Center/surround relationships of magnocellular, parvocellular, and koniocellular relay cells in primate lateral geniculate nucleus.

As in other primates, the lateral geniculate nucleus (LGN) of the prosimian primate, bush baby (Galago crassicaudatus), contains three morphologically and physiologically distinct cell classes [magnocellular (M), parvocellular (P), and koniocellular (K)] (Norton & Casagrande, 1982; Casagrande & Norton, 1991). The present study examined quantitatively the center/surround relationships of cells in all three classes. Estimates of receptive-field center size (Rc) and sensitivity (Kc) and of surround size (Rs) and sensitivity (Ks) were obtained from 47 LGN relay cells by fitting a difference of Gaussians function to contrast-sensitivity data. For M and P cells, center size (Rc) increases with eccentricity but is about two times larger for M than for P cells at a given eccentricity. Surround size (Rs) increases with eccentricity for P but not for M or K cells. The center sensitivity (Kc) is inversely related to center size (Rc) and surround sensitivity (Ks) is inversely related to surround size (Rs) for cells in all classes, a result consistent with the sensitivity regulation that is produced by light adaptation. High spatial-frequency cutoff (acuity) is inversely related to center size (Rc). However, the peak contrast sensitivity is relatively independent of Rc. The ratio of the integrated strength (volume) of the surround to the volume of the center remains relatively constant (median, 0.87) across all three cell classes. This ratio is an excellent predictor of a cell's rolloff in contrast sensitivity at low spatial frequencies: cells with a low surround/center ratio have less low-frequency rolloff. Although M, P, and K cells generally display similar center/surround relationships, differences in center size and the other parameters between the classes distinguish most M, P, and K cells. These findings demonstrate that both similarities and differences in the visual-response properties of primate LGN cells in these three parallel afferent pathways can be explained by basic center/surround relationships.

Different Types of Potassium Outward Current in Relay Neurons Acutely Isolated from the Rat Lateral Geniculate Nucleus.

Different classes of potassium (K+) outward current activated by depolarization were characterized in relay neurons acutely isolated from the rat lateral geniculate nucleus (LGN), using the whole-cell version of the patch-clamp technique. A fast-transient current (IA), activated at around - 70 mV, declined rapidly with a voltage-dependent time constant (tau=6 ms at + 45 mV), was 50% steady-state inactivated at - 70 mV, and rapidly recovered from inactivation with a monoexponential time course (tau=21 ms). IA was blocked by 4-aminopyridine (4-AP, 2 - 8 mM) and was relatively insensitive to tetraethylammonium (TEA, 2 - 10 mM). After elimination of IA by a conditioning prepulse (30 ms to - 50 mV), a slow-transient K+ current could be studied in isolation, and was separated into three components, IKm, IKs and a calcium (Ca2+)-dependent current, IK[Ca]. The slow-transient current was not consistently affected by 4-AP (up to 8 mM), while TEA (2 - 10 mM) predominantly blocked IKs and IK[Ca]. The component IKm persisted in a solution containing TEA and 4-AP, activated at around - 55 mV, declined monoexponentially during maintained depolarization (tau=98 ms at + 45 mV), was 50% inactivated at - 39 mV, and recovered with tau=128 ms from inactivation. IKs activated at a similar threshold, but declined much slower with tau=2662 ms at + 45 mV. Steady-state inactivation of IKs was half-maximal at - 49 mV, and recovery from inactivation occurred relatively fast with tau=116 ms. From these data and additional current-clamp recordings it is concluded that the K+ currents, due to their wide range of kinetics and dependence on membrane voltage or internal Ca2+ concentration, are capable of cooperatively controlling the firing threshold and of shaping the different states of electrophysiological behaviour in LGN relay cells.

The cholinergic influence upon rat dorsal lateral geniculate nucleus is dependent on state of arousal

Several lines of evidence suggest a role for acetylcholine (ACh) in mediating the effects of state of arousal on transfer of visual information through the lateral geniculate nucleus (LGN). Local application of cholinergic agonists to geniculate relay cells in anesthetized cats and rats produces predominantly facilitatory effects. This indicates that presynaptic release of ACh may be responsible for the increased excitability of LGN relay cells that is observed during waking and REM sleep. In this study in rats we have examined the influence of cholinergic agonists applied during the 3 natural states of arousal: waking, slow-wave (SW) sleep and rapid eye movement (REM) sleep. Pharmacological agents were iontophoretically administered to identified, single cells in head-restrained, unanesthetized rats free to sleep and wake. Application of cholinergic agonist produced state-dependent differences in response in all geniculate relay-cells studied. During both waking and REM sleep, a facilitatory response was always observed, whereas in SW sleep responses were of three types: no effect (62%), inhibition (24%), and biphasic inhibition followed by facilitation (14%). All response types were antagonized by scopolamine. In contrast to the qualitatively different state-dependent effects of cholinergic agonists, response to application of glutamate, with quantitatite variations, was uniformly facilitatory in all states, though responses in SW sleep tended to be lower in magnitude. The effects of γ-aminobutyric acid (GABA), glycine, and serotonin were inhibitory in all states. These data are consistent with the suggested role of ACh in mediation of increased relay-cell excitability during REM sleep and waking. Our findings, however, also indicate that in the transition from SW sleep to REM or waking, local release of ACh is not solely responsible for alterations in cell excitability.

Effects of bicuculline on signal detectability in lateral geniculate nucleus relay cells

The lateral geniculate nucleus conveys the center-surround organized retinal receptive fields to the cortex in a way that does not significantly alter their spatial structure. However, non-retinal influences may change the ‘strength’ (detectability) of the signal under conditions of anesthesia, arousal and attention. A previous analysis of receiver operating characteristic curves in cat suggests that a reduction in signal detectability occurs in lateral geniculate nucleus (LGN) relay cells in anesthetized animals in comparison to the retinal afferents. In the present study, it was found that antagonism of GABA A receptors with bicuculline (BIC) increased signal detectability in LGN relay cells in the tree shrew ( Tupaia belangeri). This change is consistent with the hypothesis that feedforward and/or feedback GABAergic circuits in the LGN differentially affect the retinogeniculate transfer ratio for visually driven activity versus maintained (spontaneous) activity. Under conditions of arousal or attention, signal detectability may be increased by brainstem activation, thus increasing the flow of information in the visual system.

Effects of bicuculline on receptive field center sensitivity of relay cells in the lateral geniculate nucleus

The lateral geniculate nucleus (LGN) receives input from the retina that is spatially organized into a receptive-field center and surround. It maintains this organization in the signal that it sends to the visual cortex. Previous studies have focused on changes in the receptive-field ‘surround’ that are generated at the LGN, possibly as a local contrast enhancement mechanism. The present study suggests a role for the LGN in regulating the receptive-field center sensitivity under the control of GABAergic circuitry. Local microiontophoresis of the GABA A receptor antagonist bicuculline increased the contrast sensitivity of LGN relay cells to many spatial frequencies. Difference of Gaussians analysis showed that the increase was due to an increased sensitivity of the receptive-field center. Similar increases in receptive-field center sensitivity may be produced during behavioral arousal by the action of pontine and mesencephalic pathways upon the activity of the LGN GABAergic circuitry.