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Traditionally, neurotransmitters are associated with a fast, or phasic, type of action on neurons in the central nervous system (CNS). However, accumulating evidence indicates that γ-aminobutyric acid (GABA) and glutamate can also have a continual, or tonic, influence on these cells. Here, in voltage- and current-clamp recordings in rat brain slices, we identify three types of tonically active receptors in a single CNS structure, the thalamic reticular nucleus (TRN). Thus, TRN contains constitutively active GABAA receptors (GABAA Rs), which are located on TRN neurons and generate a persistent outward Cl(-) current. When TRN neurons are depolarized, blockade of this current increases their action potential output in response to current injection. Furthermore, TRN contains tonically active GluN2B-containing N-methyl-D-aspartate receptors (NMDARs). These are located on reticuloreticular GABAergic terminals in TRN and generate a persistent facilitation of vesicular GABA release from these terminals. In addition, TRN contains tonically active metabotropic glutamate type 2 receptors (mGlu2Rs). These are located on glutamatergic cortical terminals in TRN and generate a persistent reduction of vesicular glutamate release from these terminals. Although tonically active GABAA Rs, NMDARs and mGlu2Rs operate through different mechanisms, we propose that the continual and combined activity of these three receptor types ultimately serves to hyperpolarize TRN neurons, which will differentially affect the output of these cells depending upon the current state of their membrane potential. Thus, when TRN cells are relatively depolarized, their firing in single-spike tonic mode will be reduced, whereas when these cells are relatively hyperpolarized, their ability to fire in multispike burst mode will be facilitated.

Transmission through the thalamus activates circuits involving the GABAergic neurons of the thalamic reticular nucleus (TRN). TRN cells receive excitatory inputs from thalamocortical and corticothalamic cells and send inhibitory projections to thalamocortical cells. The inhibitory output of TRN neurons largely depends on the level of excitatory drive to these cells but may also be partly under the control of mechanisms intrinsic to the TRN. We examined two such possible mechanisms, short-term plasticity at glutamatergic synapses in the TRN and intra-TRN inhibition. In rat brain slices, responses of TRN neurons to brief trains of stimuli applied to glutamatergic inputs were recorded in voltage- or current-clamp mode. In voltage clamp, TRN cells showed no change in alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor-mediated excitatory postsynaptic current amplitudes to stimulation at non-gamma frequencies (30 Hz), simulating background activity, but exhibited short-term depression in these amplitudes to stimulation at gamma frequencies (30 Hz), simulating sensory transmission. In current clamp, TRN cells increased their spike outputs in burst and tonic firing modes to increasing stimulus-train frequencies. These increases in spike output were most likely due to temporal summation of excitatory postsynaptic potentials. However, the frequency-dependent increase in tonic firing was attenuated at gamma stimulus frequencies, indicating that the synaptic depression selectively observed in this frequency range acts to suppress TRN cell output. In contrast, intra-TRN inhibition reduced spike output selectively at non-gamma stimulus frequencies. Thus, our data indicate that two intrinsic mechanisms play a role in controlling the tonic spike output of TRN neurons and these mechanisms are differentially related to two physiologically meaningful stimulus frequency ranges.

Transmission of sensory information through the dorsal thalamus involves two types of modality-related nuclei, first order and higher order, between which there are thought to be no intrathalamic interactions. We now show that within the somatosensory thalamus, cells in one nucleus, the ventrobasal complex, can influence activity in another nucleus, the medial division of the posterior complex. Stimulation of ventrobasal complex cells evoked inhibitory postsynaptic currents in cells of the medial division of the posterior complex. These currents exhibited the reversal potential and pharmacology of a GABAA receptor-mediated chloride conductance, indicating that they result from the activation of a disynaptic pathway involving the GABAergic cells of the thalamic reticular nucleus. These findings provide the first direct evidence for intrathalamic interactions between dorsal thalamic nuclei.

This study describes the organization of cells in the thalamic reticular nucleus (TRN) that project to the auditory part of the cat's dorsal thalamus. Injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) and fluorescent dyes were made into the medial geniculate complex (MG). The resultant retrograde labelling in the TRN was analyzed. Injections of WGA-HRP into the ventral (MGv), dorsal (MGd), or medial (MGm) nuclei of the MG label zones of cells that are restricted to a caudoventral sector of the TRN. In reconstructions, these zones resemble “slabs” that are elongated in the dorsoventral and oblique rostrocaudal dimensions of the nucleus. In comparisons of the zones of labelling in the TRN following tracer injections into different nuclei of the MG, inner and caudal cells project to the pars lateralis of the MGv (MGvl) or to the MGd, and outer and rostral cells project to the pars ovoidea of the MGv (MGvo) or to the MGm. Thus, cells projecting to the MGvl or MGd or to the MGvo or MGm occupy overlapping territories. Double injections of different fluorescent dyes into selected pairs of MG nuclei result in reticular cells that are labelled from either both nuclei or only one or the other nucleus in each pair. These results indicate that the projections of cells in the auditory sector of the TRN to the MGvl or MGvo or to the MGd or MGm are topographically organized. Furthermore, projections to more than one MG nucleus can arise from single reticular cells. J. Comp. Neurol. 390:167–182, 1998. © 1998 Wiley-Liss, Inc.

This study describes the organization of cells in the thalamic reticular nucleus (TRN) that project to the somatosensory part of the dorsal thalamus in the cat. Injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) and fluorescent dyes were made into the ventrobasal complex (VB) and the medial division of the posterior complex (POm) of the thalamus. The resultant retrograde labelling in TRN was analyzed. Large injections of a tracer in VB label many reticular cells that are restricted to a centroventral, or somatosensory, sector of TRN. Small injections of a tracer in VB produce narrow zones of labelled cells in this sector. In reconstructions these zones resemble thin “slabs,” which lie parallel to the plane of TRN along its oblique rostrocaudal dimension and occupy only a fraction of its thickness. In comparisons of the zones of labelled cells in TRN resulting from tracer injections in different nuclei of VB, inner cells, intermediate cells, and outer cells across the thickness of TRN project to the ventral posteromedial, the medial division of the ventral posterolateral, and the lateral division of the ventral posterolateral nuclei, respectively. Furthermore, shifts in injected areas along the dorsoventral dimension of VB produce similar shifts in zones of labelled cells in TRN. Thus, reticular cells form an accurate map on the basis of their connections with VB. Large injections of a tracer in the ventral subdivision of POm label many reticular cells that are also restricted to the centroventral sector of TRN. Small injections of a tracer in ventral POm produce broad zones of labelled cells in this sector. In comparisons of the zones of labelled cells in TRN resulting from tracer injections in different regions of ventral POm, cells that project to these regions are scattered across the thickness of TRN and occupy overlapping territories. Large injections of a tracer in either VB or ventral POm also label cells in a restricted centroventral region of the perireticular nucleus. Double injections of different tracers in VB and ventral POm produce many cells in TRN that are labelled from both of these dorsal thalamic structures and fewer cells that are labelled from only one or the other of these structures. These results indicate that there is a dual organization in the projections of cells in the somatosensory sector of TRN to dorsal thalamus: Projections to VB are topographically organized whereas those to ventral POm lack a topographical organization. Furthermore, both of these mapped and nonmapped projections can arise from single reticular cells in the somatosensory sector. © 1996 Wiley-Liss, Inc.

During the first week of life, there is a shift from kainate to AMPA receptor-mediated thalamocortical transmission in layer IV barrel cortex. However, the mechanisms underlying this change and the differential properties of AMPA and kainate receptor-mediated transmission remain essentially unexplored. To investigate this, we studied the quantal properties of AMPA and kainate receptor-mediated transmission using strontium-evoked miniature EPSCs. AMPA and kainate receptor-mediated transmission exhibited very different quantal properties but were never coactivated by a single quantum of transmitter, indicating complete segregation to different synapses within the thalamocortical input. Nonstationary fluctuation analysis showed that synaptic AMPA receptors exhibited a range of single-channel conductance (γ) and a strong negative correlation between γ and functional channel number, indicating that these two parameters are reciprocally regulated at thalamocortical synapses. We obtained the first estimate of γ for synaptic kainate receptors (

Transmission through the dorsal thalamus involves nuclei that convey different aspects of sensory or motor information. Cells in the dorsal thalamus are strongly inhibited by the GABAergic cells of the thalamic reticular nucleus (TRN). Here we show that stimulation of cells in specific dorsal thalamic nuclei evokes robust IPSCs or IPSPs in other specific dorsal thalamic nuclei and vice versa. These IPSCs are GABA A receptor-mediated currents and are consistent with the activation of disynaptic intrathalamic pathways mediated by TRN. Thus, cells engaged in sensory analyses in the ventrobasal complex or the medial division of the posterior complex can interact with cells responsive to sensory events in the caudal intralaminar nuclei, whereas cells engaged in motor analyses in the ventrolateral nucleus can interact with cells responsive to motor events in the rostral intralaminar nuclei. Furthermore, sensory event-related cells in the caudal intralaminar nuclei can interact with motor event-related cells in the rostral intralaminar nuclei. In addition, single cells in one dorsal thalamic nucleus can receive convergent inhibitory inputs after stimulation of cells in two or more other dorsal thalamic nuclei, and TRN-mediated inhibitory inputs can momentarily switch off tonic firing of action potentials in dorsal thalamic cells. Our findings provide the first direct evidence for a rich network of intrathalamic pathways that allows modality-related and cross-modality inhibitory modulation between dorsal thalamic nuclei. Moreover, TRN-mediated switching between dorsal thalamic nuclei could provide a mechanism for the selection of competing transmissions of sensory and/or motor information through the dorsal thalamus.

The organization of the somatosensory representation within the cat's thalamic reticular nucleus (TRN) was studied. Focal injections of horseradish peroxidase (HRP), wheatgerm agglutinin conjugated to HRP, and/or [3H]proline were made into somatosensory cortical areas 1 (S1) and 2 (S2). The resultant labelling in the thalamus was analysed. Single injections into S1 result in single zones of terminal labelling in TRN that are restricted to the centroventral part of the sheet-like nucleus. In reconstructions from horizontal sections these zones of labelling resemble thin 'slabs', which lie in the plane of the nucleus parallel to its borders, occupy only a fraction of the thickness of the reticular sheet, and are broadly elongated in the dorsoventral and oblique rostrocaudal dimensions. Thus, the slabs of S1 terminals, which represent large loci of the body surface, and the main distribution of the reticular dendrites have a similar orientation. In comparisons of the zones of labelling following single or double injections at different cortical sites in S1, an inner (medial) to outer (lateral) shift in labelling in the ventrobasal complex (VB) is accompanied by an inner (medial) to outer (lateral) shift in labelling along the thickness of the reticular sheet. Thus, like VB the reticular nucleus receives a topographically accurate projection from S1. Further, the somatotopic map conveyed from S1 to TRN is orientated perpendicular to the plane of the nucleus and repeats the spatial organization of the map in VB. S2 injections result in zones of terminal labelling in that part of TRN that receives S1 inputs. On the basis of these findings, together with those in other mammalian species, two conclusions can be reached about corticoreticular relations. First, although there can be continuity in individual maps of cortical inputs to TRN, there are discontinuities in cortical representations at the inner and outer borders of the reticular sheet. Second, TRN can receive a significant convergence of inputs from different cortical areas.

The purpose of this study was to determine the selectivity with which polyspecific antibodies directed against large retinal ganglion cells destroy axons in the cat's optic nerve. Immune serum prepared against large ganglion cells isolated from ox retinas was injected into 1 eye of each of 2 cats. After more than 1 month, the cats were perfused with mixed aldehydes and the optic nerves were prepared for transmission electron microscopy. On the basis of a large sample of micrographs of transverse thin sections, we estimated that each of the nerves that issued from treated eyes contained approximately 62,500 necrotic fibers, amounting to 42-46% of the total fiber population in 1 case and 39-42% in the other. The diameters of 2900-5000 intact axons from each of 4 nerves (2 from immune-treated eyes and 2 from untreated eyes) were measured. Comparisons of histograms of axon diameter for nerves from treated and untreated eyes revealed that 90-100% of large axons with diameters above 3.5-4.0 micron were eliminated by the antibodies. Between 65 and 70% of medium-sized fibers were also eliminated. The number of small axons--those with diameters less than 1.2-1.6 micron--did not differ appreciably from normal. These results suggest that the immune serum destroyed virtually all alpha cell axons and a substantial fraction of beta cell axons but did not reduce the number of small fibers that largely stem from the gamma class of retinal ganglion cells.

Forty-eight kittens were dark reared or light reared from birth for 1 to 8 months and formed 6 age groups. Following rearing the kittens were examined daily in several tasks of visually guided behavior. Compared to younger dark-reared groups of kittens, older deprived groups showed longer acquisition times for visual placing to a surface, visual tracking, visually guided reaching to a serrated edge and moving object, and visually guided locomotion on elevated platforms. After dark rearing durations of 3 months or longer, deprived groups displayed overall deficiencies in obstacle avoidance during their 1st postdeprivation month. The older dark-reared groups gave some indication of a direct relationship between duration of dark rearing and both delay in acquisition times for the visually guided behaviors and deficiency in obstacle avoidance. One interpretation of the results is that during dark rearing the kitten may acquire nonvisual behaviors which could interfere with and prolong its development of visually guided behavior subsequent to deprivation.

In the companion study ( Dev. Brain Res. , 34 (1987) 223–233), we showed that a monocular injection of antibodies against ox large retinal ganglion cells produces a 53% (low concentration) to 82% (high concentration) loss of Y-cells in lateral geniculate nucleus (LGN) layers A and A 1 that receive inputs from the antibody-injected eye. At the same time, the percentage of LGN X-cells is unaffected. In the present study, we investigated the effect of this monocular antibody-induced reduction of LGN Y-cells on the development of ocular dominance in striate cortex. Four-week-old kittens were given an intraocular injection of either a low (110 μg/33 μl volume) or a high (333 μg/33 μl volume) concentration of antibodies and single-cell recordings were carried out in striate cortex 33–65 weeks later. Following an injection of either antibody concentration, we found only slight abnormalities in striate cortex ocular dominance compared to normal adult cats. There was a small, but significant, decrease in the percentage of binocularly driven cells and a concomitant increase in the percentage of cells driven exclusively by the normal or control-injected eye. No ocular dominance abnormalities were found in kittens injected monocularly with control γ-globulins, indicating that the changes are due to effects of the antibodies. The changes in cortical ocular dominance produced by early antibody treatment are very different from those produced by rearing with monocular deprivation (MD) despite a similar loss of LGN Y-cells in the two conditions. This suggests that an initial (primary) monocular loss of LGN Y-cells in young kittens is not sufficient to alter cortical ocular dominance in a manner similar to that found after MD. The results thus argue against the hypothesis that the MD-induced loss of response to the deprived eye in striate cortex is secondary to a Y-cell loss in the LGN.

The cat's superior colliculus (SC) receives direct inputs from retinal W-cells (a W-D input) and Y-cells (Y-D input) and an indirect Y-cell input via the lateral geniculate nucleus and visual cortex (Y-I input). In previous studies we have shown that intraocular injection of antibodies raised against large retinal ganglion cells produces a dose-dependent reduction in the Y retinogeniculate pathway. Furthermore, when a sufficiently high antibody concentration is used, there is a substantial loss of the Y pathway and no apparent loss of the W pathway. In the present study, we used the antibodies to investigate the contributions of the Y and W pathways to functional organization within the SC. Binocular injections of low (330 micrograms/100 microliters) or high (1,000 micrograms/100 microliters) antibody concentrations were made. The antibody-mediated effects on SC cells' response properties were compared directly with effects of early binocular deprivation, which have been attributed to a loss of Y-I input. Extracellular single-cell recordings were made from the SC, and cells were classified as receiving Y-D, Y-I, or W-D inputs on the basis of their response latencies to electrical stimulation of the optic chiasm and optic tract. Injections of the low antibody concentration produced no significant effects on inputs to the SC. However, injections of the high antibody concentration resulted in a 70% reduction in SC cells with a Y-D input and an 82% reduction in SC cells with a Y-I input. There was no effect on the percentage of cells with a W-D input. Binocular deprivation produced a 76% reduction in the percentage of cells with Y-I input. Visual response properties of SC cells also were assessed. Injections of the high antibody concentration produced a 55% reduction in cells that respond with a directional preference and a 51% reduction in cells that respond to high-velocity stimuli. Binocular deprivation produced a 78% reduction in the proportion of directional cells and a 25% reduction in cells that respond to the ipsilateral eye. Taken together, the results of this and previous studies using cortical lesions, visual deprivation, and immunoablation suggest that Y-D input is the primary basis for responses to high stimulus velocity, Y-I input is an important basis for directional responses and response through the ipsilateral eye, and W-D input is important for responses to low stimulus velocity.(ABSTRACT TRUNCATED AT 400 WORDS)

A comparison was made between penicillin- and bicuculline-induced epileptiform activity. Aqueous solutions of either penicillin or bicuculline were applied to striate cortex of rabbit pups, and the electroencephalogram was monitored. Applications were made twice daily for 14 consecutive days beginning on postnatal day 8–9. During this time period, interictal spikes generated by bicuculline and penicillin displayed similar properties in most respects. However, the morphology of spikes induced by each convulsant was different.

Studies have shown that normal development of receptive field properties in striate cortex and lateral geniculate nucleus (LGN) of the rabbit is severely altered in the presence of penicillin-induced disruption of cortical neuronal activity. We wished to replicate these studies using a different convulsant drug in order to rule out possible effects due to the penicillin drug itself. Aqueous bicuculline was injected twice daily into a cannula implanted over the monocular region of one striate cortex. Drug administration was initiated on postnatal day 8–9 and was discontinued either on postnatal day 19–24 or on postnatal day 24–30 for studies of the LGN and striate cortex, respectively. Coincidental with the bicuculline injections, control solutions were similarly applied to the monocular region of the contralateral striate cortex. Single-unit recordings made from LGN ipsilateral to bicuculline-treated cortex revealed normal percentages of receptive field types. However, in single-unit recordings made from bicuculline-treated striate cortex, an abnormal percentage distribution of receptive field types was found. In such cortex there was an unusually high proportion of no-response type cells and a substantially reduced proportion of oriented type cells. These developmental abnormalities are virtually the same as those found in the striate cortex of similarly reared animals treated with penicillin. Our present results lend support to our previous conclusion that in the rabbit, disruption of orderly neuronal activity in the geniculostriate system has a detrimental effect on the development of receptive fields in this system.

We studied the long-term effects of early epileptiform activity on the development of receptive fields in the visual cortex of the rabbit. Aqueous penicillin was injected twice daily into a cannula implanted over the monocular region of one visual cortex. Drug administration was initiated on postnatal day 8–9 and was discontinued on postnatal day 24–30. Coincidental with the penicillin injections a mixture of penicillin and penicillinase was similarly applied to the monocular visual region of the contralateral (control) cortex. Following each drug administration interictal epileptiform activity was observed only from the penicillin-treated (epileptic) cortex. Single-unit recordings were made in the visual cortex 5 or 11 months after the drug-treatment period. In both 5-month and 11-month postepileptic cortex, cell samples from areas adjacent to the cannula site showed abnormal percentages of receptive field types relative to control cortex percentages. After 5 months a low proportion of oriented type cells and a high proportion of no response and indefinite type cells were found. After 11 months a low proportion of oriented type cells was also found but the proportion of no response and indefinite type cells was normal; however, an unusually high proportion of non-oriented type cells was now evident. These results indicate that although previously epileptic visual cortex eventually develops a normal complement of cells with specific receptive fields, the quantitative distribution of those cells with regard to their various functional specificity remains abnormal.

Previous studies have shown that antibodies against large retinal ganglion cells (alpha-/Y-cells) reduce the Y-cell retinogeniculate pathway while having little or no effect on the X- or W-cell pathways. The present study investigated the dose-response relationship of these effects. We began by studying effects on the T1 (largely Y-cell- mediated) and T2 (largely X-cell-mediated) waves of the retinal field- potential. Different concentrations of the antibodies were injected intraocularly in adult cats and retinal field-potentials evoked by optic chiasm stimulation were examined. The lowest concentration of immune serum tested (330 micrograms/100 microliter volume) reduced both the T1 and T2 amplitudes. With increasing concentrations, the ratio of T1:T2 amplitudes progressively decreased from 0.71 to only 0.05. The highest concentration of immune serum tested (1000 micrograms/100 microliter volume) virtually eliminated the T1 wave while the T2 wave remained (albeit reduced). Next, we carried out single-cell physiological and morphological studies to verify the effects of the highest antibody concentration and compare them with previous results on effects of the lowest antibody concentration (Kornguth et al., 1982; Spear et al., 1982). In single-cell recordings from the retina, the encounter rates of Y- and X-cells were reduced by 85 and 53%, respectively, after injection of the highest antibody concentration. There was no effect on the encounter rate of retinal W-cells. After injection of the lowest antibody concentration, there was no change in the encounter rates of any of the retinal cell types. Morphological studies revealed an 88–99% loss of alpha-cells in retinae treated with the highest antibody concentration. There also was a substantial (24– 57%) loss of medium-size ganglion cells but no loss of small ganglion cells. The loss of alpha-cells was much greater after high- concentration injections than after low-concentration injections. In recordings from the LGN, the proportion of Y-cells was reduced by 87% in laminae receiving input from an eye injected with the highest antibody concentration. Laminae receiving input from an eye injected with the lowest concentration had a 77% reduction in Y-cells. The encounter rate of LGN X-cells was not affected by either concentration. Morphological analysis indicated that the loss of Y-cells in the LGN was not due to changes in cell size. These findings indicate that antibody-mediated effects on retinogeniculate pathways are dose- dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

We examined the effects of early epileptiform activity on development of visuocortical receptive fields in the rabbit. Aqueous penicillin was injected twice a day into a cannula implanted over the monocular area of one visual cortex. Drug administration was begun on postnatal day 8-9 and continued until postnatal day 24-30. Concomitant with the penicillin injections a mixture of penicillin and penicillinase was similarly applied to the monocular area of the contralateral control cortex. Interictal discharges were routinely observed only from the penicillin-treated or epileptic cortex. Single-unit recordings made on postnatal day 25-31 revealed that in the neuronal population adjacent to the cortical penicillin focus percentages of receptive field types were severely altered relative to control cortex percentages. Epileptic cortex showed an abnormally high percentage of no response type cells together with an abnormally low percentage of complex and oriented-directional type cells. These abnormalities were greater closer to the penicillin focus than further from it. Epileptic visual cortex receptive field percentages are compared with those for the neonatal rabbit and the rabbit subjected to early monocular deprivation. One interpretation of our results is that development of complex and oriented-directional type cells is impeded by epileptogenic disruption of organized geniculostriate activity.

Previous studies have shown that pharmacological activation of presynaptic kainate receptors at glutamatergic synapses facilitates or depresses transmission in a dose-dependent manner. However, the only synaptically activated kainate autoreceptor described to date is facilitatory. Here, we describe a kainate autoreceptor that depresses synaptic transmission. This autoreceptor is present at developing thalamocortical synapses in the barrel cortex, specifically regulates transmission at frequencies corresponding to those observed in vivo during whisker activation, and is developmentally down regulated during the first postnatal week. This receptor may, therefore, limit the transfer of high-frequency activity to the developing cortex, the loss of which mechanism may be important for the maturation of sensory processing.

The postnatal development of the ipsilateral retinocollicular projection in the rabbit and the effects of unilateral enucleation (performed on the day of birth, day 0) on that development were studied by using the anterograde axonal transport of tritiated proline injected intraocularly. Material from 1-, 6-, and 10-day-old (i.e., at days 1, 6, and 10) and adult animals was examined. On day 1, autoradiographically labelled optic fibers from the ipsilateral eye formed distinct patches and bands within the superior colliculus (SC), which were restricted primarily to the lateral one-half and anterior one-third to one-half of the nucleus. At subsequent ages no major changes in the location of this projection were found for normal animals or animals enucleated on day 0 (0-DE animals). From dorsal-view reconstructions, the pattern of the ipsilateral projection appeared wedge-shaped with a broad base aligned with the lateral SC border for all normal and 0-DE animals at the various postnatal ages examined. In normal animals the surface area of this projection increased with age and maintained a constant proportion of the increasing surface area of the total SC. In 0-DE animals the surface area of the projection initially increased more rapidly than in normal animals. Thus, by day 6 the area was already within the normal adult range but did not exceed this range at later postnatal ages. The only obvious difference in the appearance of the ipsilateral retinocollicular projection between normal and 0-DE animals at corresponding ages was an enhanced radial distribution of the projection across laminae in the 0-DE animals. Taken together these findings suggest that, in the rabbit, once topographically appropriate connections are established between the SC and the ipsilateral retinal projection, they are maintained regardless of substantial postnatal growth of the SC and removal of the contralateral retinal projection to the SC.

We investigated the effects of polyclonal antibodies, produced against ox large retinal ganglion cells, on the developing retinogeniculate pathways of cats. Four-week-old kittens were given an intraocular injection of either a low or a high concentration of the antibodies and effects were assessed 35-69 weeks later. After a low concentration (110 micrograms/33 microliter volume) injection, the density of retinal alpha-cells (the morphological counterpart of Y-cells) was reduced 44% in area centralis and 37% in peripheral retina. After a high concentration (333 micrograms/33 microliter volume) injection, alpha-cell density was reduced 76% in area centralis and 91% in peripheral retina. The same concentration of antibodies had no consistent effect on the numbers of medium- or small-size retinal ganglion cells. Electrophysiological recordings from single neurons in layers A and A1 of the lateral geniculate nucleus (LGN) revealed a 53% decrease in the percentage of Y-cells after a low-concentration injection and an 82% decrease after a high-concentration injection. There was a concomitant increase in the percentage of LGN cells that were non-responsive to light or that responded too poorly to be classified. No change was observed in the percentages of LGN X-cells or cells with mixed response properties. The reduced encounter rate of LGN Y-cells was not accompanied by significant changes in LGN cell-body size. Together, the results indicate that the immunoablation technique produces a large and apparently selective reduction of the Y-cell retinogeniculate pathway in developing kittens.

The prenatal development of the rabbit's retinal projections to the superior colliculus (SC) was studied by using anterograde transport of horseradish peroxidase injected intraocularly. Fetuses aged embryonic day 21 (E21) to E29 and an adult rabbit were examined. Gestation in the rabbit is 30-31 days. On E21 contralaterally projecting retinal fibers invade across the entire SC. Their distribution is initially diffuse within the superficial laminae, but by E29 they have a distinct stratified appearance. Ipsilaterally projecting retinal fibers invade the rostral half of the SC on E21. By E23 they cover the entire SC and overlap the contralateral fibers both tangentially and radially. The ipsilateral fibers for the most part are sparsely distributed, but they form a dense focal distribution in the rostrolateral quarter of the SC. This focus straddles the stratum griseum superficiale/stratum opticum (SGS/SO) border. On E25 the ipsilateral fibers maintain their widespread distribution and focal rostrolateral concentration. By E27 they are excluded almost entirely from the caudal half of the SC and are reduced in density in the rostromedial quarter of the nucleus. On E29 the ipsilateral terminal field forms distinct patches and bands that are restricted to the rostrolateral quarter of the SC and are confined to the SGS/SO border. Thus, a few days before birth the pattern and location of the ipsilateral retinocollicular projection resemble those seen in the adult. The early widespread distribution of the ipsilaterally projecting retinal fibers to the SC and their eventual restriction in the fetal rabbit are consistent with the development of this projection in other mammalian orders.

Previous studies have shown that unilateral enucleation of rabbit pups produces an aberrant uncrossed retinotectal projection. These fibers failed to drive collicular units when stimulated with either light or electric shock. The present study attempts to assess the possibility that enucleation at earlier stages of development would lead to a greater degree of morphological and physiological reorganization in the uncrossed retinotectal projection. Rabbit fetuses were unilaterally enucleated at day 20 or 25 of gestation. Birth is at day 31. After 3 months, the degree of reorganization of the uncrossed retinotectal projection was assessed using the following techniques: (1) autoradiographic demonstration of the projection from the remaining eye, (2) electrophysiological recording of collicular unit activity, and (3) a combination of these methods. Autoradiographic data indicated a much greater expansion of the anomalous uncrossed projection in fetally enucleated animals than in those enucleated at birth. Labelled terminals were found to occupy more than the anterior third of the ipsilateral colliculus and were distributed to the entire depth of the stratum griseum superficiale and stratum opticum. Electrode penetrations within the boundaries of the expanded projection failed to locate collicular units which could be driven by either light stimulation of the eye or electric shock of the optic nerve. Only a few cells encountered in the lateral border area, receiving the normal uncrossed retinal projection, could be driven by light stimulation. These negative findings are in contrast to the data reported for the rat and hamster where anomalous retinal projections are capable of forming functional connections. Further comparative studies of reorganization are needed.

The effects of electrical stimulation of the visual cortex on superior colliculus neurons were investigated in adult Dutch-belted rabbits. Single units were recorded in the superior colliculus and classified as to receptive field type. Stimulation of the ipsilateral visual cortex activated 29% of the recorded superior colliculus units. No units were driven by stimulation of the contralateral visual cortex. Comparison of the relative proportional distributions of cortically driven and not driven cells having various receptive field types revealed an over-representation of driven motion type cells. The excitatory influence of the visuocortical projection to the superior colliculus in the rabbit shows a preference for neurons responsive to moving visual stimuli.