Unravelling the development of the visual cortex: implications for plasticity and repair

Abstract

The visual cortex comprises over 50 areas in the human, each with a specified role and distinct physiology, connectivity and cellular morphology. How these individual areas emerge during development still remains something of a mystery and, although much attention has been paid to the initial stages of the development of the visual cortex, especially its lamination, very little is known about the mechanisms responsible for the arealization and functional organization of this region of the brain. In recent years we have started to discover that it is the interplay of intrinsic (molecular) and extrinsic (afferent connections) cues that are responsible for the maturation of individual areas, and that there is a spatiotemporal sequence in the maturation of the primary visual cortex (striate cortex, V1) and the multiple extrastriate/association areas. Studies in both humans and non-human primates have started to highlight the specific neural underpinnings responsible for the maturation of the visual cortex, and how experience-dependent plasticity and perturbations to the visual system can impact upon its normal development. Furthermore, damage to specific nuclei of the visual cortex, such as the primary visual cortex (V1), is a common occurrence as a result of a stroke, neurotrauma, disease or hypoxia in both neonates and adults alike. However, the consequences of a focal injury differ between the immature and adult brain, with the immature brain demonstrating a higher level of functional resilience. With better techniques for examining specific molecular and connectional changes, we are now starting to uncover the mechanisms responsible for the increased neural plasticity that leads to significant recovery following injury during this early phase of life. Further advances in our understanding of postnatal development/maturation and plasticity observed during early life could offer new strategies to improve outcomes by recapitulating aspects of the developmental program in the adult brain.

Fig. 1

(A) Simplified diagram of the visual pathway that mediates conscious vision from the retina, through the lateral geniculate nucleus (LGN) of the thalamus to the primary visual cortex (V1). However, in addition there are also two disynaptic pathways that bypass V1 and terminate in the middle temporal (MT) area, forging through the koniocellular layers of the LGN (red) and the medial portion of the inferior pulvinar (PIm) (blue). (B) Simplified diagram of the right hemisphere of the marmoset monkey indicating the major dorsal and ventral visual stream areas (in colour). Visual information arriving at V1 is relayed to the dorsal and ventral parallel visual processing streams; the dorsal ‘where’ stream diverges from V1 towards the parietal lobe (associated areas indicated in red), whereas the ventral ‘what’ stream (associated areas indicated in green) diverges from V1 towards the temporal lobe. These broad streams incorporate the various visual areas (in colour) that are responsible for processing specific aspects of visual information. Visual areas indicated: V1, primary visual cortex; DM, dorsomedial area; DA, dorsoanterior area; DI, dorsoinferior area; PP, posterior parietal areas; MTC, middle temporal crescent; MST, medial superior temporal area; FST, fundus of the superior temporal area; IT, inferior temporal areas.

Fig. 2

Expression of Eph/ephrins in sagittal sections of marmoset brain at postnatal day (PD)0 and in adult examined by immunohistochemistry. At PD0, ephrin-A1, EphA6 and ephrin-A2 label layer 5 pyramidal cells (a, i, c) in the middle temporal (MT) area of the visual cortex. Ephrin-A1 is also expressed on axons in the white matter (b), and EphA6 is expressed on astrocytes in the white matter (ii). Low levels of EphA6, ephrin-A1 and -A2 were detected in the area MT region in adult brain.

Fig. 3

The molecular guidance cue semaphorin 3A is expressed according to an area-specific profile in the visual cortex of the maturing marmoset monkey, as revealed by immunolabelling of a sagittal section of a 7-day-old animal. At this stage of development, expression is absent in the primary visual cortex (V1); however, the adjacent area V2 reveals a strong expression profile, whereas the adjacent extrastriate area V3 shows no expression. Scale bar: 2.5 mm.

Fig. 4

Photomicrographs of medial and lateral sagittal sections immunostained for non-phosphorylated neurofilament protein (a marker of cellular maturation in a subset of pyramidal cells found throughout the visual cortex) (Lasek, 1981) from postnatal day (PD)14 and PD28 marmoset monkeys. Lateral sections reveal early maturation of the middle temporal (MT) area at PD14 before maturation of any other extrastriate area. At this stage the only other mature visual cortical area is the primary visual cortex (V1). By PD28, medial sections reveal earlier maturation of the dorsomedial (DM) area (part of the third visual complex with direct connectivity to area MT) before adjacent area V2. Both areas DM and MT are part of the dorsal stream. Ls, lateral sulcus. Scale bar: 5 mm.

Fig. 5

Schematic of the normal adult visual brain connections and hypothesized/qualified (Bridge et al. 2008) modifications following a unilateral lesion of the primary visual cortex (V1) in early life. The middle temporal (MT) area increases in size, there is an increase in size of the pulvinar (PUL) input to area MT, and an increase in callosal connectivity between the two area MTs. Also, novel contralateral connections between the contralateral geniculate nucleus (LGN) and PUL emerge.