Differential development of cation-chloride cotransporters and Cl- homeostasis contributes to differential GABAergic actions between developing rat visual cortex and dorsal lateral geniculate nucleus

A recent study suggested that gamma-aminobutyric acid (GABA) plays differential roles in activity-dependent plasticity between the visual cortex (VC) and the dorsal lateral geniculate nucleus (dLGN). In the present study, to investigate differential GABAergic functions in postnatal visual system development, the development of [Cl(-)](i), cation-Cl(-) cotransporter expression, and the [Ca(2+)](i) responses evoked by GABA were compared between VC and dLGN during the early stages of development. Using rat brain slices from postnatal days (P) 0-17, GABA-evoked [Ca(2+)](i) responses and resting [Cl(-)](i) were measured by means of optical imaging of Ca(2+) and Cl(-), respectively. Changes in the expression of cation-Cl(-) cotransporters (viz. the outwardly-directed K(+)-Cl(-) cotransporter, KCC2, and the inwardly-directed Na(+),K(+)-2Cl(-) cotransporter, NKCC1) were examined in VC and dLGN by in situ hybridization. At birth, the excitatory actions of GABA were powerful in VC, but missing in dLGN (as indicated by neuronal [Ca(2+)](i) transients), and the resting [Cl(-)](i) was significantly higher in VC than in dLGN. Signals for KCC2 mRNA expression were significantly higher in dLGN than in VC at P0. This suggests that extrusion of Cl(-) from neurons is stronger in dLGN than in VC at P0, so that a GABAergic excitatory effect was not observed in dLGN because of more negative equilibrium potential for Cl(-). The present study indicates clear differences in the molecular and physiological bases of Cl(-) homeostasis and GABA actions between the developing VC and dLGN. Such differential GABAergic actions may underlie the distinct mechanisms involved in VC and dLGN development within the visual system.     

Increased glutamate, GABA and glutamine in lateral geniculate nucleus but not in medial geniculate nucleus caused by visual attention to novelty

This study is concerned with cortico-thalamic neural mechanisms underlying attentional phenomena. Previous results from this laboratory demonstrated that the visual sector of the GABAergic thalamic reticular nucleus is selectively c-fos activated in rats that are naturally paying attention to features of a novel-complex environment, and that this activation is dependent on top-down glutamatergic inputs from the primary visual cortex. By contrast, the acoustic sector of the thalamic reticular nucleus is not activated despite noise generated by exploration and c-fos activation of brainstem acoustic centers (e.g. dorsal cochlear nucleus, inferior colliculus). A prediction of these results is that the levels of the neurotransmitters glutamate and GABA, and the glutamate-related amino acid glutamine, will be increased in the lateral geniculate nucleus (LGN), but not in the medial geniculate nucleus (MGN) of rats that explore a novel-complex environment in comparison to levels of these amino acids in control rats. By means of neurochemical analysis of these amino acids (HPLC) the results of this study confirmed this prediction. The results are consistent with the previously proposed 'focal attention' hypothesis postulating that a focus of attention in the primary visual cortex generates top-down center-surround facilitatory-inhibitory effects on geniculocortical transmission via corticoreticulogeniculate pathways. The results also supports the notion that a main function of corticothalamic pathways to relay thalamic nuclei is attention-dependent modulation of thalamocortical transmission.     

Phase locking of neuronal responses to the vertical refresh of computer display monitors in cat lateral geniculate nucleus and striate cortex

The proliferation of low-cost microcomputer systems has led to the use of these systems as alternatives to expensive display devices for visual physiology and psychophysics experiments. The video displays of these systems often lack the flexibility of achieving wide linear luminance ranges and high vertical refresh rates — two parameters which may influence data acquisition. We have examined the responses of neurons and pairs of neurons in cat LGN and striate cortex to bar and sinusoidal grating stimuli generated by a conventional PC-based VGA graphics card and displayed on a NEC Multisync + color monitor with a 60 Hz vertical (display) refresh rate. Responses to these stimuli were autocorrelated and power spectral densities (PSD) were calculated, revealing that the majority of simple and complex cortical cells and nearly all LGN cells exhibited significant peaks in their autocorrelations at 16.7 ms and in the PSD at 60 Hz. Responses to identical stimuli generated with an optical bench using an incandescent light source contained no power at 60 Hz. Furthermore, cross-correlations between the spike trains of neuron-pairs were severely contaminated by peaks directly attributable to the entrainment of the two elements of the pair to the vertical refresh signal. Thus, we suggest that the use of conventional computer displays introduces a temporal artifact into neuronal spike trains in both single and multiple spike train analysis.     

Lack of visual suppression in the rabbit lateral geniculate nucleus during blink reflex

Stimulation of the supraorbital branch of the trigeminal nerve (SO) elicited eye blinks in the rabbit, but did not decrease the amplitude of visual cortical evoked potential from stimulation of the optic chiasm (OX). In addition, the SO stimulation neither induced an inhibitory postsynaptic potential (IPSP) in LGN cells, nor activated inhibitory interneurons in the thalamic reticular nucleus (TRN), which proved to mediate both recurrent inhibition and saccadic suppression in the dorsal lateral geniculate nucleus (LGN). All these indicate that there is no visual suppression in the rabbit LGN during blink reflex.     

Structural development of the lateral geniculate nucleus and visual cortex in monkey and man

This study concerns the development of the primary visual pathway of the primate. The lateral geniculate nucleus (LGN) is the principal thalamic relay to the visual cortex (area 17), and its neurons have similar morphological characteristics in both monkey and man, as identified by Golgi impregnation. The commonest neuron is the multipolar with a radiate or tufted dendritic tree; next is the bipolar neuron with two or three diametrically opposed dendritic trunks. Less frequent are neurons with beaded dendrites and others with fine, axon-like dendritic processes, possibly interneurons. The dendritic tree of all neurons remains generally within a lamina, but some dendrites cross interlaminar zones. LGN neurons are identifiable before birth and differ from their adult form by the presence of immature features, especially numerous dendritic and somatic spines, most frequent at birth in monkeys and at about 4 months postnatally in man. They disappear almost completely by 3 months in monkeys and 9 months in man. The human LGN has reached its ‘adult’ volume by this age.Two stages in the development of the human area 17 can be defined. The first is marked by a rapid growth to its ‘adult’ volume by about 4 months, and by intense synaptogenesis beginning in the foetus and reaching a maximum around 8 months. The second stage is one of stabilization in the volume of area 17 and loss of synapses to reach ‘adult’ synaptic density around 11 years, at about 60% of the maximum values.The formation of transitory morphological features in the first weeks or months of life coincides with a period of visual plasticity in infant monkeys and humans. Our observations can be correlated with experimental evidence for visual development in monkeys and with clinical evaluation of visual activity during the human preverbal stage, a period of great importance in the establishment of visual acuity, of stereopsis and of oculomotor function, all very sensitive to the numerous forms of visual deprivation.     

Changes of visual evoked potential induced by lateral geniculate nucleus kindling in rats

PURPOSE: The present study was undertaken to investigate the changes of visual evoked potential (VEP) induced by lateral geniculate nucleus (LGN) kindling in comparison with those induced by amygdala (AMG) and hippocampus (HPC) kindling in rats. METHODS: Under pentobarbital anesthesia, the rats were fixed to a stereotaxic apparatus, and stainless steel electrodes were implanted into the LGN, AMG, HPC and the occipital cortex (OCOR). Bipolar stimulation was applied to the LGN, AMG or HPC every day until generalized seizure was obtained. VEP was recorded from the OCOR before the first day of electric stimulation (pre-kindled) and after the development of kindling (post-kindled). RESULTS: After the development of LGN kindling, the amplitudes of early VEP components (P(1)-N(1) and N(1)-P(2)) were significantly augmented in comparison with those of pre-kindled rats. In addition, the duration of the photically evoked after-discharge burst (duration of VEP) was significantly prolonged by LGN kindling. On the other hand, in AMG and HPC kindling, no significant changes were observed in VEP between pre-kindled and post-kindled rats. CONCLUSIONS: The changes of VEP observed in patients with photosensitive epilepsy are also demonstrated in animal study using LGN kindling.     

Development of neural connections between visual cortex and transplanted lateral geniculate nucleus in rats

The development of neural connections between transplanted lateral geniculate nucleus (LGN) and host visual cortex (VC) was studied in slice preparations obtained from rat brain in which a fetal (embryonic day 15–17) rat LGN was transplanted to the white matter underlying the VC of a neonate rat (postnatal day 0–1). Placing a fluorescent dye (DiI) in the transplant of the fixed slices revealed that retrogradely labeled cortical cells projecting to the transplant were broadly distributed through layers II to VI at 1 week after transplantation. Three weeks after transplantation, these cells were virtually confined to layer VI. Likewise, anterograde labeling showed that cells in the transplant sent axons up to layer I with a few branches at 1 week after transplantation, while the axons were found to terminate at layer IV with many arborizations at 3 weeks after transplantation. These observations were supported by electrophysiological studies. Analysis of the antidromic responses of the cortical cells to stimulation of the transplant showed that the efferent cells projecting to the transplant were broadly distributed in layers II–VI at 1 week after transplantation, while they were virtually restricted to layer VI at 3 weeks after transplantation. Current source-density analysis of the field potentials and intracellular analysis of the synaptic potentials in the cortical cells demonstrated that geniculocortical connections were broadly established in layers II–VI at 1 week after transplantation, and were localized to layer IV and VI at 3 weeks after transplantation. These results suggest that the development of neural connections between transplanted LGN and host VC is characterized by an initial broad distribution of afferent and efferent connections without laminar specificity, and by later selection of appropriate connections to yield lamina-specific connections comparable to those in normal adult VC.     

The visual field representation of the rat ventral lateral geniculate nucleus

The representation of the visual field in the ventral lateral geniculate nucleus (LGNv) was studied in rats anesthetized with urethane by recording the response of single units to visual stimulation. Receptive fields of LGNv units were plotted on a campimeter, 60 cm in diameter, which was placed 30 cm from the contralateral eye. LGNv neurons responded mainly to stimulation of the contralateral eye with on-tonic characteristics. Few neurons responded only to stimulation of the ipsilateral eye and no binocular interaction was observed. Retinotopic organization was clearly seen in the LGNv; the nasal visual fields were represented dorsally, the temporal fields ventrally, and the upper to lower visual fields were in the rostrolateral to caudomedial parts of the LGNv. A given point in the visual field is represented along a line running through the LGNv in a rostrocaudal direction. Almost the entire horizontal extent of the contralateral visual field was represented in the LGNv, whereas vertically the visual field between 40 degrees above and 20 degrees below the distribution axis was represented. The major axis of the strip of the visual field containing all the RF centers, which is referred to as the distribution axis, inclined nasally up and temporally down at an angle of 10.4 degrees to the 0 degree horizontal meridian line. The representation of the distribution axis in the retina was in accordance with the major axis of retinal ganglion cell distribution (Fukuda, '77; Schober and Gruschka, '77).     

Contrast invariance of orientation tuning in the lateral geniculate nucleus of the feline visual system

Responses of most neurons in the primary visual cortex of mammals are markedly selective for stimulus orientation and their orientation tuning does not vary with changes in stimulus contrast. The basis of such contrast invariance of orientation tuning has been shown to be the higher variability in the response for low‐contrast stimuli. Neurons in the lateral geniculate nucleus (LGN), which provides the major visual input to the cortex, have also been shown to have higher variability in their response to low‐contrast stimuli. Parallel studies have also long established mild degrees of orientation selectivity in LGN and retinal cells. In our study, we show that contrast invariance of orientation tuning is already present in the LGN. In addition, we show that the variability of spike responses of LGN neurons increases at lower stimulus contrasts, especially for non‐preferred orientations. We suggest that such contrast‐ and orientation‐sensitive variability not only explains the contrast invariance observed in the LGN but can also underlie the contrast‐invariant orientation tuning seen at the level of the primary visual cortex.     

Reactions of lateral geniculate cells to chemical and electrical excitation of the visual cortex in rabbits

In anesthetized and paralyzed rabbits unitary discharges of lateral geniculate nucleus (LGN) were studied after cortical excitation by strychnine and following electrical stimulation of the visual cortex (VC). Results showed that local application of strychnine produced a general increase of the spontaneous and evoked activity of geniculate cells. By contrast, cortical depression with KCl led to a differential decrement of one of the evoked responses (on or off). Electrical cortical stimulation paired with on or off stimuli led to a differential increment of on or off responses. The results support the notion that, in rabbits, the corticogeniculate system is center-surround organized. A diagrammatic model is proposed to account for the relationship between the VC and the LGN in rabbits.     

The development of glutamic acid decar☐ylase in the visual cortex and the dorsal lateral geniculate nucleus of the rat

The activity of the enzyme glutamic acid decar☐ylase was measured in the visual cortex and the dorsal lateral geniculate nucleus of the rat at several postnatal ages. The results suggest that the developmental pattern of glutamic acid decar☐ylase is reflected in the morphology of the neurons which presumably contain the enzyme.     

Development of the projections from the dorsal lateral geniculate nucleus to the lateral suprasylvian visual area of cortex in the cat.

In the study reported in the preceding paper, we used retrograde labeling methods to show that the enhanced projection from the thalamus to the posteromedial lateral suprasylvian (PMLS) visual area of cortex that is present in adult cats following neonatal visual cortex damage arises at least partly from surviving neurons in the dorsal lateral geniculate nucleus (LGN). In the C layers of the LGN, many more cells than normal are retrogradely labeled by horseradish peroxidase (HRP) injected into PMLS cortex ipsilateral to a visual cortex lesion. In addition, retrogradely labeled cells are found in the A layers, which normally have no projection to PMLS cortex in adult cats. The purpose of the present study was to investigate the mechanisms of this enhanced projection by examining the normal development of projections from the thalamus, especially the LGN, to PMLS cortex. Injections of HRP were made into PMLS cortex on the day of birth or at 1, 2, 4, or 8 weeks of age. Retrogradely labeled neurons were present in the lateral posterior nucleus, posterior nucleus of Rioch, pulvinar, and medial interlaminar nucleus, as well as in the LGN, at all ages studied. Within the LGN of the youngest kittens, a small number of retrogradely labeled cells was present in the interlaminar zones and among the cells in the A layers that border these zones. Such labeled cells were virtually absent by 8 weeks of age, and they are not found in normal adult cats. Sparse retrograde labeling of C-layer neurons also was present in newborn kittens.(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantitative analysis of the lateral geniculate nucleus in the mutant microphthalmic rat

A quantitative analysis of the lateral geniculate nucleus was carried out in the mutant microphthalmic rat. In the dorsal lateral geniculate nucleus (LGNd) of the microphthalmic rat we found the total volume and neuronal population were reduced by 45 and 68% of normal values, respectively. The size of normal LGNd neurons was 8 to 20 μm and that of mutant LGNd cells from 6 to 16 μm. Neurons of the normal LGNd were medium-size and round or oval, and their cell bodies were filled with Nissl substance. Microphthalmic LGNd neurons, on the other hand, had narrow cytoplasmic spaces with few Nissl granules, and pale cell nuclei. In the microphthalmic rat, the lateral part of the ventral lateral geniculate nucleus (LGNvl) also showed a marked reduction in the total volume and neuronal population which were 42 and 76% of normal values, respectively. The size of normal LGNvl neurons was 8 to 20 μm and that of the microphthalmic neurons from 6 to 16 μm. These findings suggested that a marked reduction in the size of the LGNd and LGNvl in the mutant can be attributed to a decrease in neuronal population to a diminution of cell size.     

Properties of cells responding to visual stimuli in the rat ventral lateral geniculate nucleus

Single-unit recordings were made of the ventral lateral geniculate nucleus (LGv) in the albino rat anesthetized with urethane. Visual receptive field properties as well as the characteristics of responses elicited by electrical stimuli to the optic tract and to the visual cortex were examined. Compared with the relay cells of the dorsal lateral geniculate nucleus (LGd), LGv cells were characterized by the following properties. (i) They responded to visual cortex stimuli orthodromically as well as to optic tract shocks. (ii) The postexcitatory inhibition they showed after single optic tract or visual cortex stimuli was only short-lasting, at most 100 ms. (iii) Conduction velocities of the optic nerve afferent fibers were mostly in the range of slow fibers, 2 to 10 m/s. (iv) The receptive fields were essentially homogeneous in type; about 90% of the sample of 53 cells were On-tonic. (v) Receptive field sizes were substantially large, from 6.3 to 45.6° (mean, 22.3°). (vi) On-tonic cells revealed a regular maintained discharge whose level changed monotonically as a function of the luminous intensity of the stimulating light. The functional implications of these findings were compared with those of the relay cells in the LGd.     

Presentation of a remote target influences visual responses of rabbit lateral geniculate cells

The described investigations analyze the influence of presenting a circumscribed target outside the limits of the classical receptive field (CRF) on the responses of lateral geniculate cells in rabbits. Animals were prepared for single cell recordings in acute experiments in the usual fashion. Cells were stimulated with a light-emitting diode (LED) positioned in the CRF and a second stimulus (S2) presented outside the field. The latter stimulus does not modify the spontaneous firing of the neuron when presented in isolation. S2 is either stationary or moving over small distances (total excursion is 3.5 degrees of arc). A moving S2 increases or decreases the responses to the LED by a greater magnitude than a stationary S2. Significantly, in 80 percent of direction-biased cells, centripetal movement of S2, that is, movement toward the receptive field, affected the neuronal discharge if it coincided with the preferred direction of the unit. These results suggest that the introduction of a remote stimulus modifies the responses of geniculate cells in rabbits.     

Origin of butyrylcholinesterase in the lateral geniculate nucleus of tree shrew

We examined the distribution and possible origins of pseudocholinesterase activity within the lateral geniculate nucleus (LGN) of the tree shrew. Butyrylcholinesterase (BuChE) activity was spread diffusely throughout the LGN and not localized to neuronal perikaryon. Lesions of the LGN eliminated this BuChE activity while not affecting acetylcholinesterase (AChE) activity; however, removal of retinal input by unilateral ocular enucleations failed to affect the BuChE activity within the denervated layers of the LGN. This lack of effect suggests that, unlike the macaque monkey, retinal terminals within the LGN of tree shrew are not the source of BuChE. Thus, in the tree shrew LGN it appears that BuChE is not metabolically related to or dependent upon AChE nor does it originate from retinal sources, but rather BuChE appears to represent an enzyme that is endogenous to the LGN.     

Changes in projection from locus coeruleus to lateral geniculate nucleus following ablation of visual cortex in adult rats

The visual cortex of adult rats was unilaterally ablated. A histofluorescence study revealed an increase of noradrenergic terminals in the lateral geniculate nucleus (LGN) ipsilateral to the decortication, confirming the previous report. Corresponding to this, the frequency for encountering neurons in the locus coeruleus (LC) activated antidromically from the LGN was increased. We suggest that LC neurons whose axon terminals were damaged by ablation of the visual cortex formed new axons or axon collaterals (pruning effect) in the LGN, thus contributing, at least partly, to the increase of noradrenergic terminals therein.