Disrupted cortical map and absence of cortical barrels in growth-associated protein (GAP)-43 knockout mice

Abstract

There is strong evidence that growthassociated protein (GAP-43), a protein found only in the nervous system, regulates the response of neurons to axonal guidance signals. However, its role in complex spatial patterning in cerebral cortex has not been explored. We show that mice lacking GAP-43 expression (؊͞؊) fail to establish the ordered whisker representation (barrel array) normally found in layer IV of rodent primary somatosensory cortex. Thalamocortical afferents to ؊͞؊ cortex form irregular patches in layer IV within a poorly defined cortical field, which varies between hemispheres, rather than the stereotypic, whiskerspecific, segregated map seen in normal animals. Furthermore, many thalamocortical afferents project abnormally to widely separated cortical targets. Taken together, our findings indicate a loss of identifiable whisker territories in the GAP-43 ؊͞؊ mouse cortex. Here, we present a disrupted somatotopic map phenotype in cortex, in clear contrast to the blurring of boundaries within an ordered whisker map in other barrelless mutants. Our results indicate that GAP-43 expression is critical for the normal establishment of ordered topography in barrel cortex.

Molecular Mechanisms, Biological Actions, and Neuropharmacology of the Growth-Associated Protein GAP-43

“…A reduced level of GAP-43 mRNA was found in the dorsolateral prefrontal cortex of post-mortem samples from patients with schizophrenia [97]. A disrupted cortical map and an absence of cortical barrels were seen in GAP-43 knockout mice [57].…”

Fibroblast Growth Factor 8 Regulates Neocortical Guidance of Area-Specific Thalamic Innervation

“…The latter appear transiently after birth in the axons of sensory thalamic nuclei, including VB Maier et al, 1999;Zhou et al, 2000). Shifted S1 barrel fields labeled for both neurochemical markers ( Fig.…”

Somatosensory cortical plasticity: recruiting silenced barrels by active whiskers

“…Several lines of evidence indicate that somatosensory periphery-related neural maps and patterns are conveyed to target cells by the afferents at each synaptic relay station Jhaveri, 1990, 1992a,b;Erzurumlu and Killackey, 1983;Senft and Woolsey, 1991). Current understanding is that topographically organized projections (somatotopic maps) along the somatosensory system are established via several axon guidance cues independent of neural activity Fukuchi-Shimogori and Grove, 2001;Maier et al, 1999;Vanderhaeghen et al, 2000). On the other hand, patterning of neural connections within "somatotopic" maps is controlled by neural activity-mediated mechanisms (Erzurumlu and Kind, 2001).…”