Time Course of Inhibition Induced by a Putative Saccadic Suppression Circuit in the Dorsal Lateral Geniculate Nucleus of the Rabbit

Psychological studies have revealed that a visual suppression occurs during the saccadic eye movements to maintain the stable visual image. This visual suppression is named saccadic suppression. A typical saccadic suppression precedes the saccadic eye movements by 30–60 ms, lasts 120–180 ms, and is followed by a 100–150-ms facilitation. Recently, we have revealed an inhibitory circuit connecting the deep layers of the superior colliculus (SC) to the dorsal lateral geniculate nucleus (LGN), via the central lateral nucleus in the thalamus (CL) and thalamic reticular nucleus (TRN). We speculated that this inhibitory circuit might mediate saccadic suppression in the rabbit. In the present study, we used intracellular recording technique to further examine the synaptic and intrinsic responses of CL cells, TRN cells, and LGN cells to the activation of this inhibitory circuit. We found that the stimulation of the deeper layers of the SC induced a fast excitation postsynaptic potential (EPSP) in CL cells, followed by a robust EPSP in TRN cells and a prolonged inhibitory postsynaptic potential (IPSP) in LGN cells. The EPSP in TRN cells was always followed by a small inhibitory postsynaptic potential (IPSP). The IPSP in LGN cells lasted about 133 ± 27 ms. Sometimes, a rebound bursting occurred after the IPSP in LGN cells. We also examined whether activation of this inhibitory circuit could suppress the retino-geniculo-cortical pathway. We found that the SC stimulation always suppressed the evoked potential in the visual cortex induced by the stimulation of the optic chiasm. Our results of the inhibitory circuit can induce an inhibition in the LGN and a suppression on the retino-geniculo-cortical pathway. The time courses of the inhibition and suppression were compatible with that of saccadic suppression revealed by psychological and physiological studies. These results support the idea that the inhibitory circuit of SC (deeper layers)-CL-TRN-LGN may mediate the saccadic suppression in the rabbit LGN. Copyright © 1996 Elsevier Science Inc.     

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.     

Cholinergic projections to the visual thalamus and superior colliculus

The parabrachial region of the brainstem reticular formation projects to the dorsal lateral geniculate nucleus of the thalamus and to the intermediate gray layer of the superior colliculus. We used the retrograde axonal transport of two fluorescent labels to demonstrate that individual parabrachial cells project to both structures. The results suggest that cholinergic cells of the parabrachial region may coordinate the relay of visuosensory information to the cortex with the onset of orienting movements.     

The superior colliculus simultaneously modifies the responses of the lateral geniculate cells and of the oculomotor nuclei

Descending and ascending influences of the superior colliculus (CS) were studied in the following way. In anesthetized and paralyzed rabbits two tungsten micro-electrodes were lowered in the (CS) and the Lateral Geniculate Nucleus (LGN) for single unit recordings. A third semi-micro-electrode (dia. 100 microns) was positioned in the vicinity of the oculomotor nuclei. The final position of this electrode was determined at a location which yielded an eye movement with the lowest intensity of the electrical pulse. The typical experimental procedures required that a spontaneous collicular spike triggered the flash presentation and data acquisition. Results indicated that collicular endogeneous activity may be capable of modifying simultaneously the evoked neuronal responses of the LGN and in the vicinity of the oculomotor nuclei.     

Local excitability in the superior colliculus influences evoked responses of lateral geniculate cells in rabbits

In anesthetized, immobilized rabbits recordings were made simultaneously from cells in the Lateral Geniculate Nucleus (CGL) and Superior Colliculus (CS), in order to study how the CS influences the CGL. The experimental protocol consisted of three steps. In the initial step (first control) the light stimulus was triggered electronically. In the second step (Test), the same stimulus was triggered by a spontaneous spike arising from a collicular cell. Thus the stimulus presentation was time-locked to collicular endogenous activity. The third step was the same as the first and constituted a second control. The frequencies of stimulus application were gated to be approximately the same. The results indicated that the CS exerts two separate effects on CGL units. In 37 pairs (26%), conditioning the stimulus presentation to collicular firing produced a significant enhancement of geniculate responses. In 24 pairs (17%), the geniculate responses declined. In 82 pairs (57%), no significant influence was noted. The colliculo-geniculate inlfuence is transient. The effects peaked between 100 to 200 msec after the collicular spike and returned to their control levels within 300 msec. Collicular cells producing a decline were encountered mostly in the ventral part of the stratum griseum superficiale, and the stratum opticum, whereas collicular cells that were related to an increased geniculate response were more frequently found dorsally. Increments were more pronounced if the distance (D) between receptive fields was short (0° < D < 40°) or if the collicular and geniculate fields were far apart (120° < D < 180°). The decrement effect was attenuated as the distance separating the two receptive fields. This study suggests that the superior colliculus is capable of generating an internal signal powerful enough to modulate at the geniculate nucleus the visual message conveyed toward the visual cortex. A possible role of the CS in the initiation of the corollary discharge is briefly discussed.     

Development and plasticity of the serotoninergic projection to the hamster's superior colliculus

Immunocytochemical techniques were employed to investigate the normal adult organization, development, and effects of both neonatal and adult eye removal upon the organization of the serotoninergic projection to the hamster's superior colliculus. Immunocytochemistry, both alone and in combination with retrograde tracing with true blue and fluorogold, was used to determine the organization of the serotoninergic projection to the superior colliculus in normal adult hamsters. Immunoreactive fibers were present in all laminae of the superior colliculus, but they were most dense in the lower part of the stratum griseum superficiale, the stratum opticum, the stratum griseum profundum, and the stratum album profundum. When retrograde tracing from the colliculus was combined with immunocytochemistry for serotonin, cells containing both labels were found in the lateral portions of the nucleus raphe dorsalis and also in periaqueductal gray, the median and pontine raphe nuclei, and in the region of the medial lemniscus. Such cells were visible both ipsilateral and contralateral to the injection site. Serotonin immunoreactive fibers were visible in the superior colliculus by embryonic day 14 (2 days prior to birth). On the day of birth, a small number of immunoreactive fibers were present just below the pial surface and others were generally oriented either parallel or orthogonal to the collicular laminae. At this age, there were also many immunoreactive fibers that crossed from one side of the brainstem to the other in the commissure of the superior colliculus. Some serotonin-positive axons appeared to terminate as growth cones in fetal and newborn hamsters. Over the next 2 weeks, the serotoninergic innervation of the SC increased in density and assumed the laminar distribution observed in adult animals. By this age, only a very few immunoreactive fibers were present in the commissure of the superior colliculus. Removal of one eye on either on the day of birth or in adulthood resulted in reorganization of the serotoninergic innervation of the partially deafferented colliculus. There was a marked increase in the density of serotonin-positive fibers in the upper stratum griseum superficiale on the side ipsilateral to the remaining eye. This change was apparent within 2 weeks after enucleation in either neonatal or adult animals. Quantitative analysis demonstrated that the magnitude of this effect was greater after adult enucleation than after neonatal eye removal. Both neonatal and adult enucleation also resulted in an increase in the density of the serotoninergic projection to the dorsal and ventral lateral geniculate nuclei ipsilateral to the remaining eye.     

Saccade-related burst neurons in cat superior colliculus

Single-unit activity was studied in the intermediate and deep layers of the superior colliculus in 4 trained cats. One class of neuron was isolated which resembles the saccade-related burst neurons (SRBNs) previously reported in monkey. These neurons produce a discrete burst of impulses preceding the onset of saccades of particular amplitudes and direction. Many of these neurons also paused during saccades in the opposite direction. Similar discharge patterns were seen when saccades were made to remember target locations as well as when a visual target was present. These findings are consistent with the idea that some neurons in the superior colliculus neurons play a role in the coding of voluntary or memory-contingent saccades as well as in the initiation of visually elicited saccades.     

Receptive field properties of rat ventral lateral geniculate cells projecting to the superior colliculus

Cells of the ventral lateral geniculate nucleus (LGV) in rats sending their axons to the superior colliculus (SC), were identified electrophysiologically as the ones responding antidromically to electrical stimulation of SC. They were located in the external part of LGV. Visual receptive fields of these cells were mostly of ON-tonic types and some of movement-sensitive ones. Evidence was presented supporting existence of the reciprocal fiber connection between the LGV and the SC.     

Increased serotoninergic innervation of the hamster's superior colliculus alters retinotectal projections

Anterograde tracing with horseradish peroxidase (HRP) was used to compare the organization of retinotectal projections in normal adult hamsters and in animals that sustained subcutaneous injections of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) on the day of birth. Neonatal injection of this neurotoxin decreases the density of the serotoninergic (5-HT) innervation of the cerebral and cerebellar cortices, but increases the density of these fibers in the brainstem including the superior colliculus (SC). Analysis of tissue from the retinorecipient laminae of the SC by high-pressure liquid chromatography indicated that these lesions increased the amount of 5-HT in the adult SC by 47%. The increased serotoninergic innervation of SC was associated with a marked change in the distribution of the uncrossed retinotectal projection. In normal adult hamsters, fibers from the ipsilateral eye form dense clusters in the lowermost stratum griseum superficiale (SGS) and stratum opticum (SO). A small number of uncrossed fibers are also visible in the more caudal portions of these layers. In the animals that sustained neonatal 5,7-DHT injections, uncrossed retinotectal fibers formed a nearly continuous band in rostral SO and lower SGS, and numerous labeled fibers were present in the caudal SC, primarily in the SO. Neonatal treatment with 5,7-DHT also produced alterations in the crossed retinotectal pathway and in the crossed and uncrossed retinogeniculate projections. These results indicate that the 5-HT input to the developing brainstem may strongly influence the development of retinofugal projections. © 1993 Wiley-Liss, Inc.     

Corticothalamic projections from layer V cells in rat are collaterals of long-range corticofugal axons

The vast majority of corticothalamic (CT) axons projecting to sensory-specific thalamic nuclei arise from layer VI cells but intralaminar and associative thalamic nuclei also receive, to various degrees, a cortical input from layer V pyramidal cells. It is also well established that all long-range corticofugal projections reaching the brainstem and spinal cord arise exclusively from layer V neurons. These observations raise the possibility that the CT input from layer V cells may be collaterals of those long-range axons projecting below thalamic level. The thalamic projections of layer V cells were mapped at a single cell level following small microiontophoretic injections of biocytin performed in the motor, somatosensory and visual cortices in rats. Camera lucida reconstruction of these CT axons revealed that they are all collaterals of long-range corticofugal axons. These collaterals do not give off axonal branches within the thalamic reticular nucleus and they arborize exclusively within intralaminar and associative thalamic nuclei where they form small clusters of varicose endings. As layer V cells are involved in motor commands everywhere in the neocortex, these CT projections and their thalamic targets should be directly involved in the central organization of motor programs.     

Projection of brain stem neurons to the perigeniculate nucleus and the lateral geniculate nucleus in the cat

Small horseradish peroxidase injections in the perigeniculate nucleus (PGN) or the lateral geniculate nucleus (LGN) gave retrograde labeling of many cells in the pontomesencephalic reticular formation (RF), the nuclei raphe dorsalis and centralis linearis, locus coeruleus, nucleus of the optic tract and nucleus parabigeminalis. Antidromic stimulation was used to identify neurons in the RF projecting to the PGN-LGN complex. Threshold mapping through the PGN and the LGN shows separate projection from the reticular formation to the PGN and the LGN.     

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.     

Visuocortical epileptiform discharges in rabbits: Differential effects on neuronal development in the lateral geniculate nucleus and superior colliculus

We have studied the effects of interictal epileptiform discharges originating from the striate cortex on the development of the receptive field characteristics of neurons in the lateral geniculate nucleus (LGNd) and superior colliculus (SC) in neonatal rabbits. The paroxysmal discharges were generated by twice-daily injections of penicillin into an implanted cannula. Control injections of penicillin + penicillinase were given to the other striate cortex of the same animal. Similar experimental procedures were used to study the effect of such projected discharges on the LGNd neurons in adult rabbit.The results of the first experiment show that cortical epileptiform discharges, initiated in neonatal rabbits 7–9 days of age and continuing to 20–25 days of age, retard the normal development of LGNd cells. There was an abnormal increase of indefinite cells, cells failing to respond to any light stimulation, and a concurrent decrease of cells with concentric or uniform receptive fields. The second experiment shows that the effect of such interictal discharges is age-dependent; they did not cause any changes on the receptive fields of LGNd cells in adult rabbit. That these epileptiform discharges, occuring early in life, had long-lasting effects is demonstrated in the third experiment. An abnormal increase of uniform cells and a concurrent decrease of concentric cells was still present in adult rabbits which had interictal discharges in the striate cortex limited to the period of 7–9 dats to 21–25 days of age. The fourth experiment shows that the interictal discharges in neonatal rabbits do not affect the normal receptive field development of neurons in the SC.The present results demonstrate that asymptomatic interictal epileptiform discharges, produced without focal structural damages in immature brain, can affect the development of neuronal connectivity. These results may have some clinical implications in relation to our understanding about the learning and developmental disabilities exhibited in children who had episodic seizure discharges.     

A substance P projection from the superior colliculus to the parabigeminal nucleus in the rat and hamster

Immunocytochemical staining with antisera directed against substance P (SP) demonstrated the existence of numerous immunoreactive neurons throughout the mediolateral and rostrocaudal extents of the stratum griseum superficiale (SGS) of the superior colliculus (SC) of both rat and hamster. In both of these species, very dense SP-like immunoreactivity (SPLI) was also visible in the parabigeminal nucleus. Combination of retrograde tracing with True blue or Fluorogold and immunocytochemistry demonstrated that SP-positive SC neurons projected to the parabigeminal nucleus in both hamster and rat. Retrogradely labelled and double-labelled cells were most numerous in the rostromedial portion of the SC and rare in the caudal portion of the colliculus. Destruction of the superficial layers of the SC resulted in a virtually complete loss of SPLI in the ipsilateral parabigeminal nucleus in both species. SPLI was also visible in two other targets of the superficial SC laminae: the intergeniculate leaflet and the ventral lateral geniculate nucleus. Ablation of the dorsal SC laminae did not reduce SPLI in either of those nuclei. Our results thus indicate that at least some tectoparabigeminal neurons in hamster and rat contain SPLI and further that the SC appears to the sole source of SP-positive input to this nucleus.     

Behavioural effects of GABA-agonists and antagonists infused in the mesencephalic reticular formation - deep layers of superior colliculus

Unilateral infusion of GABA-receptor antagonists (picrotoxin, bicuculline) in the mesencephalic reticular formation-deep layers of the superior colliculus (MRF-DLSC) elicits tight head-to-tail contralateral posturing but not active circling. Bilateral infusion of the GABA antagonists in the MRF-DLSC elicits compulsive gnawing and biting but not licking or sniffing. Infusion of GABA-receptor agonists (muscimol, THIP) in the MRF-DLSC while producing only minor or no motor or behavioural effects, drastically altered apomorphine effects; thus, unilateral infusion of muscimol resulted in tight, head-to-tail ipsiversive circling while bilateral infusion of muscimol converted the apomorphine-syndrome from stereotypy of high-intensity into a pure compulsive forward locomotion devoid of sniffing. The results indicate that GABAergic mechanisms in the MRF-DLSC are of primary importance in the expression of motor and behavioural syndromes arising from the striatum.     

Zona incerta: Substrate for contralateral interconnectivity in the thalamus of rats.

We have shown previously that the zona incerta (ZI), a small nucleus deriving from the ventral thalamus, has extensive ipsilateral connections with the higher order and intralaminar nuclei of the dorsal thalamus and that there are many ipsilateral interconnections between the different cytoarchitectonic sectors of the ZI. In this study, we explore the contralateral connections that the ZI has with its opposing nucleus as well as with the other nuclei of the thalamus. Injections of biotinylated dextran or cholera toxin subunit B were made into each of the different ZI sectors (rostral, dorsal, ventral, and caudal) and into intralaminar and higher order dorsal thalamic nuclei of Sprague-Dawley rats by using stereotaxic coordinates. Brains were fixed in aldehyde and processed using standard methods. Our results show that, after injections limited to a given ZI sector, labelled terminal-like elements and cells were seen across the other sectors of the ZI of the contralateral side. Furthermore, after each of these ZI injections, labelling was seen in the intralaminar (e.g., parafascicular, central lateral, and central medial) and higher order (e.g., posterior thalamic, lateral posterior, and lateral dorsal) nuclei of the contralateral side. These patterns of labelling were confirmed after tracer injections into intralaminar and higher order nuclei; after such injections, labelling was seen in the contralateral ZI. In all cases, there was labelling on the ipsilateral side as well, and this was generally heavier than on the contralateral side. Overall, our results indicate that there is a network of interconnections between the ZI of both sides of the thalamus and that the ZI has contralateral connections with the intralaminar and higher order nuclei. Hence, the ZI furnishes a substrate that spreads activity to both sides of the brain.     

Visual response properties of ventral lateral geniculate nucleus cells projecting to the pretectum and superior colliculus in the cat

The visual properties of cells in the cat ventral lateral geniculate nucleus (LGV) identified antidromically from the pretectum and/or superior colliculus (projection cells) were studied in comparison with those of LGV neurons which could not be activated antidromically (non-projection cells). ON-phasic receptive fields (RFs) were relatively predominant in 27 projection cells, whereas ON-tonic RFs were found more commonly in the non-projection group. The distribution of the RF centers revealed a centroperipheral gradient of the visual field representation within the LGV that the central visual field was more densely organized.     

Serotonin-mediated inhibition from dorsal raphe nucleus of neurons in dorsal lateral geniculate and thalamic reticular nuclei

Electrophysiological studies using rats anesthetized with chloral hydrate were performed to determine whether or not serotonin originating in the dorsal raphe nucleus (DR) acts as an inhibitory transmitter or neuromodulator on neurons of the dorsal lateral geniculate nucleus (LGN) and neurons located in the thalamic reticular nucleus (TRN) immediately rostral to the dorsal LGN. In the LGN, conditioning stimuli applied to the DR preceding test stimulus to the optic tract and visual cortex inhibited orthodromic and antidromic spikes in about one-third of the relay neurons and in more than half of the intrageniculate interneurons. Conditioning stimulation of the DR also produced an inhibition of the spikes elicited by stimulation of the optic tract and visual cortex of at least three-quarters of the TRN neurons. Iontophoretic application of serotonin (25 nA) inhibited the orthodromic spikes of the LGN relay neuron and TRN neuron. A close correlation was observed between the effects of DR conditioning stimulation and iontophoretic serotonin in the same neurons. The inhibition with DR conditioning stimulation and iontophoretically applied serotonin was antagonized during iontophoretic application of methysergide (15-40 nA), a serotonin antagonist. These results strongly suggest that serotonin derived from the DR acts on the LGN and TRN neurons as an inhibitory transmitter or neuromodulator to inhibit transmission in these nuclei.