Late spreding of excitation in the lateral geniculate nucleus following visual deafferentation is independent of the size of retinal lesions

Late spreading of excitation occurs in the lateral geniculate nucleus following partial retinal lesions. The extent of spreading remained the same when reducing the size of the lesions to one fifth. This is incompatible with the idea that the spreading could be caused by displacement of normal cells into the deafferented area as a consequence of transneuronal volume reduction.     

Synaptic reorganization in the dorsal lateral geniculate nucleus following damage to visual cortex in newborn or adult cats

We have studied the effects of making large lesions of visual cortex on the synaptic organization of the dorsal lateral geniculate nucleus (LGN) in the cat. Visual cortex was removed at birth in one group of cats and during adulthood in a second group. Following survival periods of 6 months to 2 years, the organization of synapses made by afferents from the retina in the LGN was investigated quantitatively with the electron microscope. In single thin sections we determined the percentage of retinal axon terminals that made synapses in the LGN, the average number of synapses made by each retinal axon terminal, and the identity of each postsynaptic process. These measurements were made separately for retinogeniculate connections in the A and C laminae of the LGN. For comparison, similar sets of measurements were made in adult cats that had been reared normally. When single thin sections from the A or C laminae of the LGN in normal cats are examined, about 60% of the axon terminals from the retina are seen to make at least one synaptic contact. These contacts can be with dendrites or F profiles or both. On average, each retinogeniculate terminal makes approximately 1.4 synapses in the plane of a single section and contacts dendrites three times as often as F profiles. In the A laminae of the LGN in cats that received a visual cortex lesion at birth or in adulthood, the percentage of retinal terminals that make synapses is the same as in normal cats. Similarly, the average number of synaptic contacts made by each retinogeniculate terminal is not changed by a lesion of visual cortex. In contrast, the number of contacts made with dendrites is reduced markedly, by about 29% after a lesion at birth and 53% after a lesion as an adult. However, these reductions are offset by compensatory increases in the number of contacts made with F profiles, and thus the mean number of contacts made by each retinogeniculate terminal is stabilized at a normal value. In the C laminae of the LGN, retinogeniculate terminals also reapportion their synaptic contacts. In cats with a lesion during adulthood, the redistribution of synapses is compensatory, as in the A laminae. When a lesion is made at birth, however, the number of new retinal contacts made with F profiles exceeds the number of dendritic contacts that are lost. As a result, each retinogeniculate terminal makes about 26% more synapses, in total, than normal.(ABSTRACT TRUNCATED AT 400 WORDS)     

Evolution of morphological and histochemical changes in the adult cat cuneate nucleus following forelimb denervation

Morphological and histochemical changes were studied in the ipsilateral cuneate nucleus between one and 52 weeks after forelimb denervation in adult cats. The deafferented nucleus and neighboring fasciculus were noticeably reduced in size within four weeks and decreased further by 13 weeks. The intensity of acetylcholinesterase staining decreased within one week and was further reduced one month after nerve transections. This reduction in acetylcholinesterase staining was transient, approaching control levels within one year. Parvalbumin immunostaining was also altered by the nerve transections; on the deafferented side, the neuropil staining in the cuneate nucleus and fasciculus decreased, but the number of parvalbumin-positive cells was consistently greater than in the contralateral side. These cell counts returned to normal levels within one year. One month after the injury, cytochrome oxidase activity was reduced. This reduction persisted and was even more apparent after one year. In parallel, the cell clusters of the nucleus became progressively less distinct. These observations in an adult mammal indicate that peripheral nerve injury imposes molecular and morphological changes on second-order sensory neurons which evolve differentially with time. Although some changes developed rapidly after deafferentation, the onset of others was slower; and whereas some seemed irreversible, others eventually regressed. Taken together with the functional studies of others, these findings suggest that early molecular changes observed in cuneate neurons reflect adaptive reactions to lesion-induced alterations in afferent activity. Permanent deprivation of the normal input, however, would eventually lead to chronic, and perhaps irreversible, degenerative changes. © 1996 Wiley-Liss, Inc.     

A study of Golgi preparations from the dorsal lateral geniculate nucleus of the adult cat

Four cell types are distinguishable in the lateral geniculate nucleus. The largest (class 1) have their dendrites oriented in relation to the plane of the laminae. The dendrites cross laminar borders freely and bear many fine spines. Class 2 cells show less orientation of their dendrites. These dendrites bear clusters of grape-like appendages close to the branching points and fine spines on their peripheral segments. Only the peripheral segments cross laminar borders. The smallest (class 3) cells have long stalked appendages and give rise to intrinsic axons which ramify close to the perikaryon. Cell classes 1 and 2 occur in laminae A and A1, with class 1 cells mainly concentrated between laminae. Class 3 cells occur in all major laminae. Class 4 cells, with long smooth dendrites oriented parallel to the lamina, lie in lamina B. Two types of extrinsic axon are seen. Type I axons give off many short simple terminal collaterals which often innervate more than one lamina. These are regarded as extra-retinal afferents. Type II axons (probably retinal afferents) have complex flower-like terminals and each axon innervates only one lamina. Contacts between several type II axons and two or more grape-like clusters occur in laminae A and A1. In lamina B finer type II axons form complex overlapping terminal nests around the dendrites of class 4 cells.     

Ventral lateral geniculate nucleus projects to the dorsal lateral geniculate nucleus in the cat

The lamina C3 of the dorsal lateral geniculate nucleus of the cat does not receive retinal projections but instead receives visual information from the small subpopulation of W-type ganglion cells via the upper substratum of the stratum griseum superficiale of the superior colliculus. We herein report a projection from the lateral division of the ventral lateral geniculate nucleus into the lamina C3 of the dorsal lateral geniculate nucleus. As the lateral division receives projections from the contralateral retina and the ipsilateral upper stratum griseum superficiale of the superior colliculus, we suggest that these regions make up a small cell type W-cell neuronal network that provides visual information to layer I of the striate cortex via the lamina C3.     

Increased transneuronal excitation of the cat lateral geniculate nucleus after acute deafferentation

Single neurons and sum potentials were recorded from the cat optic tract (OT), the lateral geniculate nucleus (LGN) and the optic radiation (OR) before and after visual deafferentation obtained by locally restricted photocoagulation of the retina or by 'total' photocoagulation of the optic disc of 'monocular' cats. Immediately after deafferentation, the spontaneous activity of single LGN-neurons fell to a very low level (is much less than 0.1 impulses/sec). This nearly total depression of neuronal activity was followed by a slow but incomplete recovery of the spontaneous impulse rate which reached about 1-2 impulses/sec, 2-4 days after deafferentation. The 'normal' LGN neuron impulse rate was about 8-30 impulses/sec. After deafferentation the impulse pattern showed an increased occurrence of double discharges separated by very long intermittent intervals. The excitability of LGN principal cells activated by OT electrical stimuli increased immediately after deafferentation. Double and multiple discharges were then elicited by single optic tract stimuli. The deafferentation hyperexcitability was abolished temporarily by OT stimulus trains with a frequency range > 10 stimuli/sec, and returned to the prestimulus level within 0.5-1sec after the stimulus train was terminated. Antidromic conditioning stimuli did not influence the deafferentation hyperexcitability. The time course of the postdeafferentation hyperexcitability was separated into two parts: an immediate rise in excitability after deafferentation was followed by a further slow increase in excitability within the first 2 h after deafferentation. The hyperexcitability measurable at a single unit level was already maximal after locally restricted deafferentation and did not increase with the extension of the retinal lesion beyond 1-2 mm diameter, corresponding to 4-8 degrees in the visual field. Intracellular recordings after deafferentation displayed no significant increase in the amplitude of subthreshold EPSPs, but additional slow, aperiodic, depolarizing waves were found to modify the resting membrane potential. From the multiple discharge pattern elicited by single OT electrical stimuli, one can conjecture that the suprathreshold EPSPs, however, increased considerably in their amplitude. The evoked potentials (OR-waves r1, r2) elicited by electrical OT stimuli increased in amplitude and the small waves r3-r6 became more prominent after deafferentation. All postsynaptic r-waves reached their maximum values about 1.5 h after interruption of the optic nerve signal flow and did not change further within the following 28 h.     

Inhibition from ventral tegmental area of nucleus accumbens neurons in the rat

The role of the ventral tegmental area (VTA), which is rich in dopamine-containing cell bodies, on nucleus accumbens (Acc) neurons was examined. In Acc neurons receiving input from parafascicular nucleus (Pf) of thalamus, VTA conditioning stimulation produced an inhibition of spike generation with Pf stimulation. In contrast, VTA conditioning stimulation did not affect Acc neurons receiving input from limbic structures such as the amygdala nucleus and hippocampus.     

Primary afferent plasticity following deafferentation of the trigeminal brainstem nuclei in the adult rat

Alpha-tyrosinated tubulin is a cytoskeletal protein that is involved in axonal growth and is considered a marker of neuronal plasticity in adult mammals. In adult rats, unilateral ablation of the left facial sensorimotor cortical areas induces degeneration of corticotrigeminal projections and marked denervation of the contralateral sensory trigeminal nuclei. Western blotting and real-time-PCR of homogenates of the contralateral trigeminal ganglion (TG) revealed consistent overexpression of growth proteins 15 days after left decortication in comparison with the ipsilateral side. Immunohistochemical analyses indicated marked overexpression of α-tyrosinated tubulin in the cells of the ganglion on the right side. Cytoskeletal changes were primarily observed in the small ganglionic neurons. Application of HRP-CT, WGA-HRP, and HRP to infraorbital nerves on both sides 15 days after left decortication showed a significant degree of terminal sprouting and neosynaptogenesis from right primary afferents at the level of the right caudalis and interpolaris trigeminal subnuclei. These observations suggest that the adaptive response of TG neurons to central deafferentation, leading to overcrowding and rearrangement of the trigeminal primary afferent terminals on V spinal subnuclei neurons, could represent the anatomical basis for distortion of facial modalities, perceived as allodynia and hyperalgesia, despite nerve integrity.     

Discontinuities in the dorsal lateral geniculate nucleus corresponding to the optic disc: A comparative study

A cylindrical cellular discontinuity commonly occurs in lateral geniculate layers that are innervated by the contralateral eye. Such a discontinuity has been found in a variety of mammalian species, including carnivores, primates, a rodent and a marsupial. Electrophysiological evidence obtained from some of these species shows that the discontinuity corresponds to the blind spot. It is concluded that the representation of the retina within the lateral geniculate nucleus is extremely accurate, since the retinal receptor layer and the geniculate layers have corresponding holes. Two possible mechanisms that would demand such a discontinuity are considered. One is an intralaminar mechanism in which the cells in each lamina accurately reflect the distribution of retinal receptors; the other is an interlaminar mechanism in which the representations of the homonymous hemiretinae are so accurately aligned that the optic disc must be represented by a cellular discontinuity.     

Genesis of interneurons in the dorsal lateral geniculate nucleus of the cat

Most neurons in the A-laminae of the cat's dorsal lateral geniculate nucleus (LGN) are born between embryonic days 22 and 32. Whereas approximately 78% of these cells are destined to become geniculocortical relay cells, the remaining 22% of LGN neurons do not appear to establish connections with visual cortex, and therefore can be considered interneurons. In the present study we have combined the 3H-thymidine method for labeling dividing neurons with the retrograde horseradish peroxidase (HRP) method for identifying LGN relay cells in order to study specifically the genesis of interneurons in the cat's LGN. Developing LGN interneurons in 12 kittens were labeled with 3H-thymidine by injecting the radioactive label into the allantoic cavity of their pregnant mothers on different embryonic days. Approximately 8-22 weeks after birth LGN relay cells in the A-laminae were labeled retrogradely by injecting large volumes of HRP into visual cortex areas 17 and 18. LGN cells that could not be labeled retrogradely with HRP were considered to be interneurons. Our results show that interneurons are born on each of the embryonic days studied, E24-E30. This period represents approximately the middle two-thirds of the entire period of LGN neurogenesis. Although the birth rate for interneurons is not uniform, there is no indication from our data that interneurons and relay cells in the cat's LGN are born at different times during LGN neurogenesis.     

A quantitative study of the complex laminated body in the lateral geniculate nucleus of the cat

A quantitative study has been made of the proportions and distribution of cells with complex laminated bodies (CLBs) in the lateral geniculate nucleus of the cat. They develop between 55 and about 70 days postnatal and are distributed irregularly across the medio-lateral extent of lamina A. There was no indication that the proportion of cells with CLBs is higher in the region of lamina A where the area centralis is represented, but the proportion in the binocular segment as a whole was higher than for the monocular segment. In kittens reared with unilateral or bilateral eyelid suture the proportions of cells with CLBs was above normal in the deprived laminae and below normal in the undeprived laminae.     

Genesis of neurons in the dorsal lateral geniculate nucleus of the cat

Neurons that will ultimately form the dorsal and ventral lateral geniculate nuclei, the medial interlaminar nucleus, the perigeniculate nucleus, and the nucleus reticularis of the cat undergo their final cell division beginning on, or slightly before, embryonic day 22 (E22) and ending on, or before, E32. Early in this period, neurogenesis proceeds for all of these geniculate nuclei, whereas only in the dorsal lateral geniculate nucleus does cell birth continue until E32. Distinct spatiotemporal gradients of cell birth are not obvious within any of the individual geniculate nuclei. For the dorsal lateral geniculate nucleus in particular, and for the other geniculate nuclei in general, neurons born early in this period exhibit a full range of adult soma sizes, including large and small neurons. Neurons born late in this period exhibit only small adult somas. The location and size of a neuron within the dorsal lateral geniculate nucleus provide clues to that cell's functional properties. On the basis of presently available information regarding the relationship between structure and function of neurons in the cat's dorsal lateral geniculate nucleus, the findings described here suggest that all functional classes of neurons in the dorsal lateral geniculate nucleus are born at the same time throughout most of this period.     

Electrophysiological and morphological correlates of axotomy-induced deafferentation of the goldfish Mauthner cell

Axotomy-induced changes in afferent synapses to the goldfish Mauthner cell have been analyzed with intracellular recordings and with electron microscopy. The studies encompassed 7-208 days after cervical spinal cord transection. The physiological findings suggest a persistent and specific reduction in excitatory chemical inputs to the soma and proximal lateral dendrite, with no changes in somatic inhibition or in the electrotonic and chemical inputs to the more distal regions of the lateral dendrite. Corroborative morphological evidence includes swelling of the M-cell soma, as indicated by a 35% increase in the length of its minor diameter, an increased spacing and a quantitatively lower density of terminals on the soma, and the appearance of astrocytic processes partially or completely engulfing the terminals in that region. Similar changes were observed on the inferior dendrites projecting from the ventral surface of the soma, although these dendrites do not exhibit the chromatolytic changes observed at the soma. In contrast, there are no noticeable changes in either the synaptic investment of the lateral dendrite or its ultrastructure. Quantitative and qualitative data support the conclusion that there is a restricted and specific reduction in the proximal excitatory inputs to the M-cell. The evidence also suggests that electrotonic junctions between afferents and the M-cell remain intact, functionally and structurally.     

Abnormal axonal growth in the dorsal lateral geniculate nucleus of the cat

Retino-geniculate axons in the cat were induced to grow abnormally by cutting one optic nerve in kittens. Surviving optic tract axons that had grown into the denervated regions were then filled in the adults with horseradish peroxidase to reveal the terminal arbors of individual axons. Two types of abnormal axonal growth are described—translaminar growth and monocular segment growth. Translaminar growth is the most common and occurs between lamine in the binocular part to the nucleus. Axons giving rise to translaminar growth do not branch as they pass through the denervated regions of the nucleus. Instead, the abnormal branches originate from portions of the terminal arbor within the normal target lamina. These axons look like normal retino-geniculate axons in terms of their branching patterns, cytological features, and patterns of synaptic contacts except that parts of their terminal arbors have expanded to innervate inappropriate laminae. The distribution of translaminar branches overlaps the distribution of a restricted group of surviving large neurons that have not undergone denervation atrophy. Monocular segment growth invades the lateral pole of the nucleus directly from the optic tract. These branches arise from axons passing through or near the denervated region and appear to represent the formation of new terminal arbors. The synaptic swellings arising from these branches have cytological features like the synaptic swellings arising from translaminar branches and they from similar patterns of synaptic contacts. However, monocular segment branches degenerate more rapidly when damaged and they are not associated with surviving large neurons.     

Retinal ganglion cell degeneration following loss of postsynaptic target neurons in the dorsal lateral geniculate nucleus of the adult cat.

Kainic acid was used to produce selective degeneration of neurons in the dorsal lateral geniculate nucleus of the adult cat. This degeneration mimics the rapid loss of geniculate neurons seen after visual cortex ablation in the neonate. Following survivals of 2, 4, or 6 months, the geniculate was injected with horseradish peroxidase and the retinae were examined for the presence of retrogradely labeled cells. Analysis of ganglion cell density in peripheral nasal retina revealed a 58% loss of cells overall at 6 months. The proportion of cells labeled with horseradish peroxidase decreased more rapidly, until none were labeled at 6 months. Separate analysis of small, medium, and large ganglion cell populations revealed that only medium-sized cells were lost at 2 months whereas both medium and large cells were lost at 4 and 6 months. By 6 months, 92% of medium cells and 65% of large cells had degenerated. These results show that mature retinal ganglion cells in the cat maintain a dependence on target integrity for their continued survival. When the appropriate target is lost, the ganglion cells respond first by axon terminal retraction and then by cell death.     

Y retinal terminals contact interneurons in the cat dorsal lateral geniculate nucleus

One of the largest influences on dorsal lateral geniculate nucleus (dLGN) activity comes from interneurons, which use the neurotransmitter gamma-aminobutyric acid (GABA). It is well established that X retinogeniculate terminals contact interneurons and thalamocortical cells in complex synaptic arrangements known as glomeruli. However, there is little anatomical evidence for the involvement of dLGN interneurons in the Y pathway. To determine whether Y retinogeniculate axons contact interneurons, we injected the superior colliculus (SC) with biotinylated dextran amine (BDA) to backfill retinal axons, which also project to the SC. Within the A lamina of the dLGN, this BDA labeling allowed us to distinguish Y retinogeniculate axons from X retinogeniculate axons, which do not project to the SC. In BDA-labeled tissue prepared for electron microscopic analysis, we subsequently used postembedding immunocytochemical staining for GABA to distinguish interneurons from thalamocortical cells. We found that the majority of profiles postsynaptic to Y retinal axons were GABA-negative dendrites of thalamocortical cells (117/200 or 58.5%). The remainder (83/200 or 41.5%) were GABA-positive dendrites, many of which contained vesicles (59/200 or 29.5%). Thus, Y retinogeniculate axons do contact interneurons. However, these contacts differed from X retinogeniculate axons, in that triadic arrangements were rare. This indicates that the X and Y pathways participate in unique circuitries but that interneurons are involved in the modulation of both pathways.     

A quantitative study of the effects of monocular enucleation and deprivation on cell growth in the dorsal lateral geniculate nucleus of the cat

Systematic, quantitative studies are presented concerning the effects of visual deprivation and deafferentation on the growth of developing neurons in the dorsal lateral geniculate nucleus of the cat. Three sets of experiments are described. In the first set, kittens were enucleated monocularly at one week postnatal, and sacrificed at intervals that ranged from one day to 40 weeks. The second set was similar in design, but enucleation was done at four weeks postnatal. The third series of experiments did not involve enucleation. Instead, kittens were deprived by suturing the lids of one eye closed at the time of normal eye opening. They were then allowed to survive for periods of time that varied from two to 32 weeks. In addition, two cats were studied that had been deprived for 16 weeks by sewing the nictitating membrane across the cornea of one eye. Cell counts in the binocular segment of lamina A indicate that enucleation at one week postnatal leads to rapid cell death in the lateral geniculate nucleus. Approximately 27% of deafferented cells die during the first week after enucleation. Comparable cell loss also occurs in kittens enucleated at four weeks, but its onset is delayed until the second week following eye removal. There is no loss of neurons in the lateral geniculate in cats raised with monocular eyelid suture. Measurements of cell sizes show that the primary effect of visual deprivation or deafferentation is to alter the growth of lateral geniculate neurons. In deprived kittens or those enucleated at one week, affected cells continue to grow, albeit slower than normal, for 3–4 weeks postoperatively, at which time all further cell growth stops. Subsequently, there is no marked cellular atrophy, and deprived or deafferented neurons remain at approximately two-thirds normal size. Enucleation at four weeks produces more severe effects. Eye removal arrests cell growth immediately, and approximately one month later deafferented neurons undergo significant atrophy. In these cats as well as in visually deprived animals, lateral geniculate cells receiving uncrossed input from the retina undergo greater changes in perikaryal size than neurons innervated contralaterally. In each set of experiments, rates of cell growth were compared in the binocular and monocular segments of lamina A ipsilateral and contralateral to the operated eye. No major differences were found between cells in the binocular segment and those in the dorsal portion of the monocular segment (that part of the monocular segment that lies adjacent to the lateral border of lamina A1). Furthermore, in enucleated cats, cell size changes throughout the deafferented monocular segment are equivalent, in general, to those in the binocular segment. By contrast, in visually deprived cats, neurons in the dorsal and ventral parts of the monocular segment respond differently. The present results suggest that a gradient of susceptibility to deprivation exists in the monocular segment since neurons located in the dorsal portion of the monocular segment are affected similarly to binocular segment cells, whereas cells in the ventral part ofthe monocular segment are resistant to deprivation. Neurons in the normally innervated binocular segment of lamina A in deprived or deafferented cats tend to grow somewhat faster than cells in normal animals, but do not attain larger than normal sizes. These experiments therefore do not provide evidence that normally innervated lateral geniculate neurons hypertrophy following monocular deprivation or enucleation.