Low-intensity repetitive transcranial magnetic stimulation improves abnormal visual cortical circuit topography and upregulates BDNF in mice.

Repetitive transcranial magnetic stimulation (rTMS) is increasingly used as a treatment for neurological and psychiatric disorders. Although the induced field is focused on a target region during rTMS, adjacent areas also receive stimulation at a lower intensity and the contribution of this perifocal stimulation to network-wide effects is poorly defined. Here, we examined low-intensity rTMS (LI-rTMS)-induced changes on a model neural network using the visual systems of normal (C57Bl/6J wild-type, n = 22) and ephrin-A2A5(-/-) (n = 22) mice, the latter possessing visuotopic anomalies. Mice were treated with LI-rTMS or sham (handling control) daily for 14 d, then fluorojade and fluororuby were injected into visual cortex. The distribution of dorsal LGN (dLGN) neurons and corticotectal terminal zones (TZs) was mapped and disorder defined by comparing their actual location with that predicted by injection sites. In the afferent geniculocortical projection, LI-rTMS decreased the abnormally high dispersion of retrogradely labeled neurons in the dLGN of ephrin-A2A5(-/-) mice, indicating geniculocortical map refinement. In the corticotectal efferents, LI-rTMS improved topography of the most abnormal TZs in ephrin-A2A5(-/-) mice without altering topographically normal TZs. To investigate a possible molecular mechanism for LI-rTMS-induced structural plasticity, we measured brain derived neurotrophic factor (BDNF) in the visual cortex and superior colliculus after single and multiple stimulations. BDNF was upregulated after a single stimulation for all groups, but only sustained in the superior colliculus of ephrin-A2A5(-/-) mice. Our results show that LI-rTMS upregulates BDNF, promoting a plastic environment conducive to beneficial reorganization of abnormal cortical circuits, information that has important implications for clinical rTMS.

Knockdown of the candidate dyslexia susceptibility gene homolog dyx1c1 in rodents: effects on auditory processing, visual attention, and cortical and thalamic anatomy.

The current study investigated the behavioral and neuroanatomical effects of embryonic knockdown of the candidate dyslexia susceptibility gene (CDSG) homolog Dyx1c1 through RNA interference (RNAi) in rats. Specifically, we examined long-term effects on visual attention abilities in male rats, in addition to assessing rapid and complex auditory processing abilities in male and, for the first time, female rats. Our results replicated prior evidence of complex acoustic processing deficits in Dyx1c1 male rats and revealed new evidence of comparable deficits in Dyx1c1 female rats. Moreover, we found new evidence that knocking down Dyx1c1 produced orthogonal impairments in visual attention in the male subgroup. Stereological analyses of male brains from prior RNAi studies revealed that, despite consistent visible evidence of disruptions of neuronal migration (i.e., heterotopia), knockdown of Dyx1c1 did not significantly alter the cortical volume, hippocampal volume, or midsagittal area of the corpus callosum (measured in a separate cohort of like-treated Dyx1c1 male rats). Dyx1c1 transfection did, however, lead to significant changes in medial geniculate nucleus (MGN) anatomy, with a significant shift to smaller MGN neurons in Dyx1c1-transfected animals. Combined results provide important information about the impact of Dyx1c1 on behavioral functions that parallel domains known to be affected in language-impaired populations as well as information about widespread changes to the brain following early disruption of this CDSG.

Switching retinogeniculate axon laterality leads to normal targeting but abnormal eye-specific segregation that is activity dependent.

Partial decussation of sensory pathways allows neural inputs from both sides of the body to project to the same target region where these signals will be integrated. Here, to better understand mechanisms of eye-specific targeting, we studied how retinal ganglion cell (RGC) axons terminate in their thalamic target, the dorsal lateral geniculate nucleus (dLGN), when crossing at the optic chiasm midline is altered. In models with gain- and loss-of-function of EphB1, the receptor that directs the ipsilateral projection at the optic chiasm, misrouted RGCs target the appropriate retinotopic zone in the opposite dLGN. However, in EphB1(-/-) mice, the misrouted axons do not intermingle with normally projecting RGC axons and segregate instead into a distinct patch. We also revisited the role of retinal activity on eye-specific targeting by blocking correlated waves of activity with epibatidine into both eyes. We show that, in wild-type mice, retinal waves are necessary during the first postnatal week for both proper distribution and eye-specific segregation of ipsilateral axons in the mature dLGN. Moreover, in EphB1(-/-) mice, refinement of ipsilateral axons is perturbed in control conditions and is further impaired after epibatidine treatment. Finally, retinal waves are required for the formation of the segregated patch of misrouted axons in EphB1(-/-) mice. These findings implicate molecular determinants for targeting of eye-specific zones that are independent of midline guidance cues and that function in concert with correlated retinal activity to sculpt retinogeniculate projections.

Imaging studies in congenital anophthalmia reveal preservation of brain architecture in 'visual' cortex.

The functional specialization of the human brain means that many regions are dedicated to processing a single sensory modality. When a modality is absent, as in congenital total blindness, 'visual' regions can be reliably activated by non-visual stimuli. The connections underlying this functional adaptation, however, remain elusive. In this study, using structural and diffusion-weighted magnetic resonance imaging, we investigated the structural differences in the brains of six bilaterally anophthalmic subjects compared with sighted subjects. Surprisingly, the gross structural differences in the brains were small, even in the occipital lobe where only a small region of the primary visual cortex showed a bilateral reduction in grey matter volume in the anophthalmic subjects compared with controls. Regions of increased cortical thickness were apparent on the banks of the Calcarine sulcus, but not in the fundus. Subcortically, the white matter volume around the optic tract and internal capsule in anophthalmic subjects showed a large decrease, yet the optic radiation volume did not differ significantly. However, the white matter integrity, as measured with fractional anisotropy showed an extensive reduction throughout the brain in the anophthalmic subjects, with the greatest difference in the optic radiations. In apparent contradiction to the latter finding, the connectivity between the lateral geniculate nucleus and primary visual cortex measured with diffusion tractography did not differ between the two populations. However, these findings can be reconciled by a demonstration that at least some of the reduction in fractional anisotropy in the optic radiation is due to an increase in the strength of fibres crossing the radiations. In summary, the major changes in the 'visual' brain in anophthalmic subjects may be subcortical, although the evidence of decreased fractional anisotropy and increased crossing fibres could indicate considerable re-organization.

Phr1 regulates retinogeniculate targeting independent of activity and ephrin-A signalling.

Proper functioning of the mammalian visual system requires that connections between the eyes and their central targets develop precisely. At birth, axons from the two eyes project to broad, overlapping regions of the dorsal-lateral geniculate nucleus (dLGN). In the adult, retinal axons segregate into distinct monocular regions at stereotyped locations within the dLGN. This process is driven by both molecular cues and activity-dependent synaptic competition. Here we demonstrate that Phr1, an evolutionarily conserved regulator of synapse formation and axon guidance, defines a novel molecular pathway required for proper localization of retinogeniculate projections. Following conditional excision of Phr1 in the retina, eye-specific domains within the dLGN are severely disturbed, despite normal spontaneous retinal wave activity and monocular segregation. Although layer placement is dramatically altered, Phr1 mutant retinal axons respond to ephrin-A in vitro. These findings indicate that Phr1 is a key presynaptic regulator of retinogeniculate layer placement independent of activity, segregation, or ephrin-A signaling.

Relay of visual information to the lateral geniculate nucleus and the visual cortex in albino ferrets.

The abnormal organization of the central visual pathways in the albino ferret has been characterized anatomically and physiologically. Recordings in dorsal lateral geniculate nucleus of the albino ferret show that lamina A1, which receives an aberrant projection from the contralateral eye, contains an extensive representation of the ipsilateral visual hemifield with receptive fields located up to 35 degrees from the vertical meridian. This is not the case in pigmented ferrets, for which the vast majority of units, activated through either the contralateral or ipsilateral eye, have receptive fields confined to the contralateral hemifield. The few fields found in the ipsilateral hemifield are driven through the contralateral eye and none is more than 10 degrees from the midline. Cortical topography was studied by making closely spaced electrode penetrations across the area 17/18 border. In pigmented animals, the reversal of topography at the border is characterized by units with receptive fields centered a few degrees into the ipsilateral hemifield. In 22 of 25 albinos, the "Boston" aberrant topography was found: the representation of the vertical meridian is within area 17, rather than at the area 17/18 border. Instead, at the area 17/18 border, there is a reversal in the topographic progression at up to 30 degrees into the ipsilateral hemifield. This pattern was most pronounced in the upper visual field. In agreement with the "Boston" physiology, injections of retrograde tracer made in area 17 usually label neurons in either lamina A or the part of lamina A1 that is aberrantly innervated by the contralateral eye. A column of labeled cells extending through all geniculate layers is rarely seen in albinos, although this is commonly the pattern in pigmented ferrets.

Time course of the effects of prenatal gamma irradiation on the dorsal lateral geniculate nucleus of Swiss mice.

A previous study reported that adult mice irradiated at the 16th embryonic day present a severe neuronal number reduction in the dorsal lateral geniculate thalamic nucleus. In the present study, we investigated the time course of the effects of prenatal irradiation on this thalamic nucleus. One day after irradiation, a great number of pyknotic figures were seen mainly in the cerebral proliferative zones. In the geniculate nucleus, only scattered pyknotic figures were identified. On the first week after birth, the geniculate nucleus presented frequent pyknotic figures. From five days after birth onwards, a severe shrinkage of the occipital cortex and a great reduction in the geniculate nucleus neuronal number were found. On the second week after birth this neuronal number reduction reached as high as 75%. At each postnatal analyzed age, severe volumetric geniculate nucleus shrinkage was combined to non-significant neuronal density variations. The presence of few pyknotic figures in the geniculate nucleus one day after irradiation and its delayed neuronal loss indicate an indirect effect of irradiation. We suggest that the effect upon the geniculate nucleus is secondary to the damage of the occipital cortex. A possible interpretation for thalamic neuronal loss is that geniculate neurons fail to establish cortical arbors after major target loss. In this case, the loss of trophic support should also be considered.

Abnormal retinotopic organization of the dorsal lateral geniculate nucleus of the tyrosinase-negative albino cat.

Visual defects associated with hypopigmentation have been studied extensively in Siamese and albino cats. Previous research on tyrosinase-negative albino cats has shown that (1) approximately 95% of all nasal and temporal retinal fibers cross at the optic chiasm, and (2) ocular dominance columns normally found in cortex are replaced with hemiretinal domains. In this study, we compared the retinotopic organization of the dorsal lateral geniculate nucleus (LGNd) and visual cortex in albino cats. Extracellular recordings were conducted in the LGNd, area 17, and area 18 of six albino cats. Receptive fields (RFs) were plotted for all sites. We find that, as in albino visual cortex, the albino LGNd contains (1) normal cells with RFs in the visual hemifield contralateral to the recording site (RFc), (2) abnormal cells with RFs in the ipsilateral hemifield (RFi), (3) abnormal cells with dual, mirror-symmetric RFs, one in each hemifield (RFd), and (4) abnormal cells with broad RFs that span the vertical meridian (RFb). Our data indicate that lamina A and lamina A1 consist predominantly of normal RFc and abnormal RFi cells, respectively. The C laminae contain a mixture of RFc, RFi, RFd, and RFb cells. The interlaminar zones contained RFd cells, RFb cells, or both. Thus, the albino LGNd is arranged into hemiretinal and not ocular dominance laminae. Finally, the percentage of normal cells is significantly larger in area 17 (84%) and area 18 (70%) than in the LGNd (46%), suggesting a suppression of abnormal activity in albino cat cortex, which could underlie the existing competence of visual function in albinos.

Visual search performance in dyslexia.

According to the magnocellular theory of dyslexia, otherwise intelligent children may fail to learn to read because of abnormalities in the magnocellular layers of the lateral geniculate nucleus (mLGN). If this were the case, one would predict that dyslexic subjects who show a deficit on low-level psychophysical tasks which tax the magnocellular system would also have deficits on higher-level visual tasks which do not rely on the properties of mLGN cells but depend upon the functioning of areas whose main inputs originate in the mLGN. In other words, magnocellular deficits should be traceable at later stages of visual processing. One area where such later processing is thought to occur is the posterior parietal cortex, damage to which impairs function on some classes of visual search. To test this hypothesis, we tested two groups of dyslexic subjects and a group of non-dyslexic controls on a range of visual search tasks. One group of dyslexic subjects had elevated motion coherence thresholds, a sign of deficits at the early levels (e.g. mLGN) of visual processing, and the other group had normal motion coherence thresholds. If the magnocellular deficits extended to the parietal cortex, it follows that the subjects with elevated motion coherence thresholds should have deficit in visual search, whereas those with normal motion coherence thresholds should not. The dyslexics with a motion coherence deficit were also impaired on serial visual search tasks but not on a parallel search. The dyslexics with normal motion coherence performance were unimpaired on visual search. The deficit was expressed as an elevation in reaction times, but there was no difference between the groups either in error rates or in the way the tasks were ranked according to difficulty. The results suggest that those dyslexics who have visual problems related to magnocellular functions also have visual-attentional problems related to the functions of areas such as the parietal cortex, which are dominated by inputs originating in the magnocellular LGN.

Activation of human extrageniculostriate pathways after damage to area V1.

We have used positron emission tomography (PET) to specify the cortical and subcortical structures activated following visual stimulation of the scotomatous field in a patient with an asymmetric bilateral developmental anomaly of the visual cortex. Computerized perimetry indicated a left visual field defect only although MRI and 18FDG-PET scans showed abnormalities in both occipital lobes. The visual stimuli were semicircular gratings moving in opposite directions on a dynamic random-dot background. They were specifically constructed to eliminate intra- and extraocular light scatter and to optimize the activation of extra-striate cortical areas and their projecting subcortical relays. For anatomical localization PET images were coregistered to the subject's MRI in Talairach coordinates. After subtraction of the baseline conditions from the stimulation conditions, a t-statistic map was created on a voxel-by-voxel basis. Stimulation of the scotomatous hemifield yielded significant activations of Brodmann cortical areas 18-19 and 47 as well as the pulvinar thalami of the left hemisphere, in addition to a less prominent activation in the right hemisphere. Stimulation of the intact hemifield produced significant activation of Brodmann cortical areas 30 and 47 of the left hemisphere. These results suggest that in the absence of area V1, residual vision observed in the blind hemifield could be mediated by a retinofugal pathway to extrastriate cortex via the pulvinar.

A morphological anomaly of the dorsal lateral geniculate nucleus in Macaca fascicularis.

In the present report we describe a morphological anomaly of the thalamus. In three macaque monkeys (Macaca fascicularis), we observed up to five finger-like protrusions that emanated from the posterior pole of the dorsal lateral geniculate nucleus (LGN) and extended posteriorly between the lateral pulvinar and reticular nucleus of the thalamus. These anomalous fingers measured up to 1.7 mm in length and contained dense accumulations of neurons and glia. The fingers received a direct retinal input from the contralateral eye indicating that they were part of the LGN rather than of other adjacent thalamic nuclei. In order to determine with which subcompartment(s) of the LGN the fingers were associated (parvocellular, magnocellular, or intercalated layers), we examined the immunochemical properties and size of neurons in the fingers and LGN subcompartments. We concluded that the fingers were not associated with the intercalated layers, since neurons in the fingers did not stain with an antibody to calbindin-D28k, whereas intercalated neurons stained intensely with this antibody. In addition, neurons located in the fingers were significantly smaller than those found in the magnocellular layers but were not significantly different in size from neurons in the parvocellular layers. We therefore consider that the fingers are an anomaly of the parvocellular subcompartment of the LGN. Interestingly, in two of the three cases with anomalous fingers, we also observed subsidiary parvocellular laminae, suggesting that these two anomalies were related. In five additional animals, however, we observed subsidiary parvocellular laminae without anomalous fingers. Thus, if there are common mechanisms underlying the development of both anomalous fingers and subsidiary layers, our data indicate that they do not always result in the concomitant expression of both anomalies.

Severe sensory deficits but normal CNS development in newborn mice lacking TrkB and TrkC tyrosine protein kinase receptors.

Analysis of mice carrying targeted mutations in genes encoding neurotrophins and their signalling Trk receptors has provided critical information regarding the role that these molecules play in the mammalian nervous system. In this study we generated mice defective in both TrkB and TrkC tyrosine kinase receptors to determine the biological effects of these receptors in the absence of compensatory mechanisms. trkB(-/-);trkC(-/-) double-mutant mice were born at the expected frequency, indicating that TrkB and TrkC signalling are not required for embryonic survival. However, these double-mutant mice had a significantly shorter lifespan and displayed more severe sensory defects than their single-mutant trkB(-/-) and trkC(-/-) littermates. The most dramatic sensory deficit observed in trkB(-/-);trkC(-/-) mutant mice was the absence of vestibular and cochlear ganglia. Interestingly, these mice developed inner ear sensory epithelia in spite of the complete absence of sensory innervation. Analysis of the CNS in trkB(-/-);trkC(-/-) mutant mice revealed a well formed hippocampus, cortex and thalamus. Moreover, the pattern of expression of several neuronal markers appeared normal in these animals. These observations suggest that neurotrophin signalling through TrkB and TrkC receptors is essential for the development of sensory ganglia; however, it does not play a major role in the differentiation and survival of CNS neurons during embryonic development.

Target recognition and visual maps in the thalamus of achiasmatic dogs.

Vision is dependent on ordered neuronal representations or maps of visual space. These maps depend on precise connections between retinal axons and their targets cells. In mammals, nerve fibres from right and left eyes produce congruent maps of contralateral visual space in adjacent layers of the lateral geniculate nucleus (LGN). We have identified an autosomal recessive mutation in Belgian sheepdogs that eliminates the optic chiasm. In these mutants, all retinal axons project into the ipsilateral optic tract, including those originating in the nasal hemiretina that normally cross midline. These animals exhibit a pronounced horizontal nystagmus. The abnormal ipsilaterally directed nasal fibres innervate the LGN as if they had successfully crossed the midline, terminating in the appropriate layer of the nucleus. As a consequence, the LGN contains non-congruent, mirror-image maps of visual space in adjacent layers. These results show that there is a robust affinity between nasal and temporal retinal axons and specific LGN layers even when all retinal axons originate from a single eye.

Induction of somatic sensory inputs to the lateral geniculate nucleus in congenitally blind mice and in phenotypically normal mice.

The incidence of aberrant innervation of the lateral geniculate nucleus by ascending somatic sensory axons was examined following injections of wheat germ agglutinin conjugated with horseradish peroxidase into the dorsal column nuclei of adult mice which were: (1) normal; (2) normal, but bilaterally enucleated on the day of birth; (3) normal, but received a large unilateral lesion of the rostral cortex on the day of birth; (4) normal, bilaterally enucleated, as well as unilaterally lesioned in the rostral cortex on the day of birth; (5) homozygous for an ocular retardation mutation (orj/orj); or (6) homozygous for the orj mutation and received a large unilateral lesion of the rostral cerebral cortex on the day of birth. In the phenotypically normal animals which were untreated, no somatic sensory inputs enter into the dorsal lateral geniculate nucleus. A few labeled axons enter into and arborize within the dorsal lateral geniculate nucleus in normal animals which received bilateral enucleations or unilateral rostral cortical lesions on the day of birth. However, in congenitally blind animals and in phenotypically normal animals which received bilateral enucleations as well as unilateral rostral cortical lesions on the day of birth, a significant number of labeled axons enter into and arborize within the dorsal lateral geniculate nucleus. Among all these experimental groups, the densest innervation of the lateral geniculate nucleus occurred in congenitally blind animals which received rostral cortical lesions on the day of birth. In these, robust arborizations of labeled somatic sensory axons occupy a substantial extent of the lateral geniculate nucleus. These results not only demonstrate that ascending somatic sensory axons can be rerouted to the lateral geniculate nucleus, but also indicate that the ability of a thalamic afferent pathway to undergo extensive reorganization and to innervate inappropriate thalamic targets following early perturbations is not unique to the retinal projection (in which this has previously been demonstrated), and may be a more general characteristic of the major thalamic afferent systems.

An abnormal retinal projection to the lateral posterior nucleus in micrencephalic rats.

The retinofugal projections of albino rats made micrencephalic by prenatal exposure to the cytotoxic teratogen methylazoxymethanol acetate (MAM Ac) have been examined. The only abnormality noted was an increased projection to the lateral posterior nucleus of the thalamus in rats exposed to MAM Ac on embryonic day 15. The relatively normal retinofugal projections were surprising in view of the extensive damage induced by prenatal exposure to this drug.

The normal and abnormal postnatal development of retinogeniculate projections in golden hamsters: an anterograde horseradish peroxidase tracing study.

In adult hamsters, the dorsal lateral geniculate nucleus (LGd), which lacks a noticeable pattern of cellular lamination, receives fibers predominantly from the contralateral eye except for a medial segment which receives fibers from the ipsilateral eye. Using the method of anterograde transport of horseradish peroxidase (HRP), it is shown in this study that the contralateral and ipsilateral retinogeniculate fibers innervate the LGd by day 0 with the development of the contralateral fibers slightly ahead of the ipsilateral ones. The entire contralateral LGd is filled with retinal fibers by day 1. The ipsilateral LGd is almost completely covered with retinal fibers on day 2 but with the fiber density much higher in the dorsal half of the nucleus. Thus, fibers from both eyes overlap with each other completely beginning on day 2 in the LGd. The segregation of these fibers becomes obvious on day 6 as indicated by a decrease in the density of ipsilateral fibers in the ventral portion of the LGd while the ipsilateral projection continues to concentrate in the dorsal half of the nucleus. A low density area in the dorsomedial part of the contralateral LGd is observed on day 7. By day 8, the segregation of the contralateral and ipsilateral projections has achieved an adult-like pattern. Thus, there seems to be two phases for the normal development of the retinogeniculate fibers. In the first phase, axons from both eyes grow in and occupy the entire LGd. In the second phase, those axons occupying inappropriate areas of the LGd are eliminated to form the adult pattern. The effect of unilateral eye removal at birth on the development of the retinogeniculate projection from the remaining eye was also studied with the anterograde HRP method. The ipsilateral fibers in the experimental animals are distributed in the lateral portion of the nucleus in the first two postnatal days. The entire LGd is not filled with ipsilateral fibers until day 4. From day 6 onwards, the ipsilateral fibers are more extensive than those of the normal animals. In addition to a dense projection to the dorsal two-thirds of the LGd, moderate amount of ipsilateral axons can be detected in the remaining ventral portion of the nucleus in day 6 and older experimental animals. The development of the contralateral retinal fibers in the experimental animals is similar to that of the normal from day 1 to day 6, i.e. the entire LGd is densely filled with crossed optic axons.(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormal retino-geniculate and geniculo-cortical pathways in several genetically distinct color phases of the mink (Mustela vison).

Several genetically distinct color phases of mink, which all show an abnormal reduction of pigment in the retinal pigment epithelium and which also show abnormalities of the retinofugal pathways, have been studied. Autoradiographic methods have been used to demonstrate the retino-geniculate pathways, and retrograde degeneration or the retrograde transport of horseradish peroxidase has been used for the geniculo-cortical pathways. The retino-geniculate abnormality is mild in some of the color phases and extremely severe in others, but within any one color phase the variability is relatively low. Although the severity of the abnormality varies between color phases, a rather specific pattern of abnormal geniculate innervation is recognizable for mink in general and this is distinct from that found in Siamese cats. In the abnormal mink the size of geniculate lamina A1 is reduced and there is an abnormal crossed input going to the intermediate sectors of this reduced layer. Layer C1 also receives an abnormal crossed input, but this is more variable than that going to A1 and there appears to be little correspondence, retinotopically, between the normal inputs to layers A1 and C1. In some of the abnormal mink there are interruptions within the cytoarchitectionically definable layer A1, and opposite these gaps reduplications of layer A are commonly seen, as though there is an intrinsic geniculate mechanism for generating the characteristic multilaminar geniculate structure. However, there are also numerous examples of fusions between layers receiving afferents from the same eye, and these demonstrate that the development of geniculate lamination must also be under the influence of the retinal inputs. The geniculo-cortical pathway shows a normal topography in most of the mink. Abnormal geniculo-cortical projections, comparable to the "Boston" pattern of Siamese cats are extremely rare, and their occurrence could not be correlated with the severity of the retino-geniculate abnormality or with the laminar pattern in the lateral geniculate nucleus. We suggest that the development of one or the other pattern of geniculo-cortical projection may depend upon the relative timing of the two mechanisms that produce the geniculate lamination.

Abnormal retinogeniculate projections in the congenitally microphthalmic cat.

The retinogeniculate projections from the normal eye of a unilaterally microphthalmic cat are abnormal in that optic tract fibers cross laminar borders and end, inappropriately, in geniculate layers that would normally receive input from the microphthalmic eye. This congenitally induced abnormal retinogeniculate projection is quite similar to that seen in cats with one eye surgically removed shortly after birth. Although most cells are shrunken in the laminae normally innervated by the microphathalmic eye, cells in the region of the abnormal projection appear normal. The normal pattern of geniculate lamination is also disrupted in that cell-free interlaminar regions are considerably more difficult to define in the microphthalmic cat.