Pattern formation by retinal afferents in the ferret lateral geniculate nucleus: developmental segregation and the role of N-methyl-D-aspartate receptors.

The projection from the retina to the lateral geniculate nucleus (LGN) in ferrets segregates during development into eye-specific layers and ON/OFF sublayers. The projection pattern and the morphology of single axons was examined at several postnatal ages. The axons progress from a simple, sparsely branched morphology at birth to crude arbors at postnatal day 7 (P7). At P14-P15, axons have terminal arbors that span one eye-specific layer. By P19-P21, retinal afferents in the A layers have segregated into inner and outer sublaminae that correspond to ON- and OFF-center cells. Sublaminae form mainly by directed growth of terminal arbors in appropriately positioned regions of the LGN, along with elimination of extraneous branches in inappropriate regions. From P28 to P35, the LGN assumes an adult-like shape, and retinogeniculate axons form terminal boutons on branch endings. During the period between P14 and P21, when retinogeniculate axons segregate into ON/OFF sublaminae, N-methyl-D-aspartate (NMDA) receptors were blocked with chronic infusion of specific antagonists into the LGN. NMDA receptor blockade prevents the retinal afferent segregation into ON/OFF sublaminae. Some individual retinogeniculate axons have arbors that are not restricted appropriately, and most are restricted in size but are located inappropriately within the eye-specific laminae. Thus, NMDA receptor blockade prevents the positioning of retinogeniculate arbors that lead to the formation of ON/OFF sublaminae in the LGN. These results indicate that the activity of postsynaptic cells, and the activation of NMDA receptors in particular, can influence significantly the patterning of inputs and the structure of presynaptic afferents during development.

Cortically induced thalamic plasticity in the primate somatosensory system.

The influence of cortical feedback on receptive field organization in the thalamus was assessed in the primate somatosensory system. Chronic and acute suppression of neuronal activity in primary somatosensory cortex resulted in a striking enlargement of receptive fields in the ventroposterior thalamus. This finding demonstrates a dramatic 'top-down' influence of cortex on receptive field size in the somatosensory thalamus. In addition, this result has important implications for studies of adult neuronal plasticity because it indicates that changes in 'higher-order' areas of the brain can trigger extensive changes in the receptive field characteristics of neurons located earlier in the processing pathway.

A role for nitric oxide in the development of the ferret retinogeniculate projection.

The ferret retinogeniculate projection segregates into eye-specific layers during the first postnatal week and into ON/OFF sublaminae, which receive inputs from either on-center or off-center retinal ganglion cells, during the third and fourth postnatal weeks. The restriction of retinogeniculate axon arbors into eye-specific layers appears to depend on action potential activity () but does not require activation of NMDA receptors (). The formation of ON/OFF sublaminae is also activity-dependent and is disrupted by in vivo blockade of NMDA receptors (). To investigate a possible mechanism whereby blockade of postsynaptic NMDA receptors in the lateral geniculate nucleus (LGN) results in changes in the size and position of presynaptic axon arbors, we tested the role of the diffusible messenger nitric oxide (NO) in the development of the retinogeniculate pathway. We found previously that NO synthase (NOS) is transiently expressed in LGN cells during the refinement of retinogeniculate projections (). In this study, treatment with NG-nitro-L-arginine (L-NoArg), an arginine analog that inhibits NOS, during the third and fourth postnatal weeks resulted in an overall pattern of sublamination that was significantly reduced compared with normal and control animals. Single retinogeniculate axon arbors were located in the middle of eye-specific layers rather than toward the inner or outer half as in normal or control animals. The effect of NOS inhibition was not a consequence of the hypertensive effect of L-NoArg. In contrast to the effect of L-NoArg on the formation of ON/OFF sublaminae, treatment with L-NoArg during the first postnatal week did not disrupt the formation of eye-specific layers. Biochemical assays indicated significant inhibition of NOS during both treatment periods. These data suggest that NO acts together with NMDA receptors in activity-dependent refinement of connections during a specific phase of retinogeniculate development.

Disruption of retinogeniculate afferent segregation by antagonists to NMDA receptors.

Afferent activity has an important role in the formation of connections in the developing mammalian visual system. But the extent to which the activity of target neurons shapes patterns of afferent termination and synaptic contact is not known. In the ferret's visual pathway, retinal ganglion cell axons from each eye segregate early in development into eye-specific laminae in the lateral geniculate nucleus (LGN). The dorsal laminae (termed laminae A and A1) then segregate further into inner and outer sublaminae that retain input from on-centre and off-centre retinal axons, respectively. Thus, individual retinogeniculate axons form terminal arbors within laminae A and A1 that are restricted to one inner or outer sublamina. We report here that blockade of N-methyl-D-aspartate (NMDA) receptors on LGN cells with specific antagonists during the period of sublamina formation prevents retinal afferents from segregating into 'On' and 'Off' sublaminae. Retinogeniculate axons have arbors that are not restricted appropriately, or are restricted in size but inappropriately positioned within the eye-specific laminae. NMDA receptor antagonists may specifically disrupt a mechanism by which LGN neurons detect correlated afferent and target activity, and have been shown to reduce retinogeniculate transmission more generally, causing LGN cells to have markedly reduced levels of activity. These results therefore indicate that the activity of postsynaptic cells can significantly influence the patterning of inputs and the structure of presynaptic afferents during development.

A map of visual space induced in primary auditory cortex.

Maps of sensory surfaces are a fundamental feature of sensory cortical areas of the brain. The relative roles of afferents and targets in forming neocortical maps in higher mammals can be examined in ferrets in which retinal inputs are directed into the auditory pathway. In these animals, the primary auditory cortex contains a systematic representation of the retina (and of visual space) rather than a representation of the cochlea (and of sound frequency). A representation of a two-dimensional sensory epithelium, the retina, in cortex that normally represents a one-dimensional epithelium, the cochlea, suggests that the same cortical area can support different types of maps. Topography in the visual map arises both from thalamocortical projections that are characteristic of the auditory pathway and from patterns of retinal activity that provide the input to the map.

Maturation of projections from occipital cortex to the ventrolateral geniculate and superior colliculus in postnatal hamsters.

The development of corticofugal axons from the posterior cortex of young (ages P3-P11, P15 and P22) and adult Syrian hamsters was investigated by anterograde axonal transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). On P3 and P4, 30 h after tracer was deposited in the cortex, The HRP reaction product was observed in the dorsal nucleus of the lateral geniculate body and in the lateral posterior nucleus of the thalamus, but no labeled axons were observed in the ventral nucleus of the lateral geniculate body (LGBv) until P5. Axon arborization, indicated by a granular precipitate scattered throughout the LGBv was light on P6 and robust on P7. Adult-like patterns of cortico-LGBv innervation were present by P11. The time course for the development of corticotectal fibers was similar to that for the cortico-LGBv projection: labeled cortical efferents were present in the pretectum on P5, but these did not enter the optic fiber layer of the superior colliculus (SC) until the following day (P6). Substantial invasion of the superficial gray layer, resulting from possible arborization of cortical axons in the optic fiber layer, occurred on P9. An adult-like distribution was evident by P11. Thus, corticofugal efferents to the LGBv and to the SC follow a similar developmental sequence, with the LGBv afferents maturing slightly earlier. There appears to be, however, a significant difference in the 'waiting periods' for the two systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Visualizing anterogradely transported HRP by use of TMB histochemistry: comparison of the TMB-SNF and TMB-AHM methods.

Horseradish peroxidase (HRP), a commonly used enzymatic marker for tracing pathways in the central nervous system, can be visualized histochemically with the aid of the chromogen tetramethyl benzidine (TMB). In a recent report, Olucha and collaborators (J Neurosci Meth 13:131, 1985) introduced the use of ammonium heptamolybdate (AHM) as a substitute for sodium nitroferricyanide (SNF) which serves to stabilize the HRP reaction product. This TMB-AHM method of Olucha et al. proves superior to the TMB-SNF method of Mesulam (J Histochem Cytochem 26:106, 1978) in that the reaction does not produce crystalline artifact. For visualization of retrogradely transported HRP, the two methods are reportedly equivalent in sensitivity. In the work reported here, we have compared the sensitivity of the two methods in detecting HRP that was transported anterogradely after intraocular injections of the enzyme in normal adult and neonatal hamsters, as well as in animals with lesions of the superior colliculus or retina. We demonstrate that the TMB-SNF method is decidedly more sensitive than the TMB-AHM technique for visualization of anterogradely transported HRP. This difference in sensitivity is especially evident in regions of sparse projections.