A Model for Cortical Rewiring Following Deafferentation and Focal Stroke

Current thinking about long-term memory in the cortex is focused on changes in the strengths of connections between neurons. But ongoing structural plasticity in the adult brain, including synapse formation/elimination and remodelling of axons and dendrites, suggests that memory could also depend on learning-induced changes in the cortical 'wiring diagram'. Given that the cortex is sparsely connected, wiring plasticity could provide a substantial boost in storage capacity, although at a cost of more elaborate biological machinery and slower learning.

Although new and functional neurons are produced in the adult brain, little is known about how they integrate into mature networks. Here we explored the mechanisms of synaptogenesis on neurons born in the adult mouse hippocampus using confocal microscopy, electron microscopy and live imaging. We report that new neurons, similar to mature granule neurons, were contacted by axosomatic, axodendritic and axospinous synapses. Consistent with their putative role in synaptogenesis, dendritic filopodia were more abundant during the early stages of maturation and, when analyzed in three dimensions, the tips of all filopodia were found within 200 nm of preexisting boutons that already synapsed on other neurons. Furthermore, dendritic spines primarily synapsed on multiple-synapse boutons, suggesting that initial contacts were preferentially made with preexisting boutons already involved in a synapse. The connectivity of new neurons continued to change until at least 2 months, long after the formation of the first dendritic protrusions.

The cortical representations of the hand in area 3b in adult owl monkeys were defined with use of microelectrode mapping techniques 2-8 months after surgical amputation of digit 3, or of both digits 2 and 3. Digital nerves were tied to prevent their regeneration within the amputation stump. Successive maps were derived in several monkeys to determine the nature of changes in map organization in the same individuals over time. In all monkeys studied, the representations of adjacent digits and palmar surfaces expanded topographically to occupy most or all of the cortical territories formerly representing the amputated digit(s). With the expansion of the representations of these surrounding skin surfaces (1) there were severalfold increases in their magnification and (2) roughly corresponding decreases in receptive field areas. Thus, with increases in magnification, surrounding skin surfaces were represented in correspondingly finer grain, implying that the rule relating receptive field overlap to separation in distance across the cortex (see Sur et al., '80) was dynamically maintained as receptive fields progressively decreased in size. These studies also revealed that: the discontinuities between the representations of the digits underwent significant translocations (usually by hundreds of microns) after amputation, and sharp new discontinuous boundaries formed where usually separated, expanded digital representations (e.g., of digits 1 and 4) approached each other in the reorganizing map, implying that these map discontinuities are normally dynamically maintained. Changes in receptive field sizes with expansion of representations of surrounding skin surfaces into the deprived cortical zone had a spatial distribution and time course similar to changes in sensory acuity on the stumps of human amputees. This suggests that experience-dependent map changes result in changes in sensory capabilities. The major topographic changes were limited to a cortical zone 500-700 micron on either side of the initial boundaries of the representation of the amputated digits. More distant regions did not appear to reorganize (i.e., were not occupied by inputs from surrounding skin surfaces) even many months after amputation. The representations of some skin surfaces moved in entirety to locations within the former territories of representation of amputated digits in every monkey studied. In man, no mislocation errors or perceptual distortions result from stimulation of surfaces surrounding a digital amputation.(ABSTRACT TRUNCATED AT 400 WORDS)