Efferent and afferent connections of mouse sensory-motor cortex following cholinergic deafferentation at birth.
The present study investigates the effect of cholinergic basal forebrain lesions at birth on cortical connectivity in adulthood. We have previously shown that such neonatal lesions result in extensive cortical cholinergic deafferentation during early postnatal development, which is accompanied by abnormal morphogenesis of cortical cytoarchitecture (Höhmann at al., 1988). Here, we have used WGA-HRP to label anterogradely and retrogradely afferent and efferent projections of dorsal neocortex. Our results show an altered projection pattern from dorsal thalamus to layer IV of sensory-motor cortex following lesions among the cholinergic basal forebrain neurons (nBM), while corticothalamic projections from layer VI appear normal. In addition, corticofugal projections from layer V, labeled by striatal injection, appear to be expanded following the lesion. This indicates that cortical layers undergoing differentiation after the newborn nBM lesion present with long-term abnormalities in connectivity. The present results are compatible with the hypothesis that cholinergic afferents are instrumental in the regulation of cortical morphogenesis. Furthermore, our data show that ontogenetic disturbances can lead to structural abnormalities that persist long after the initial deficiency has abated. We discuss the significance of these results in relationship to human neurological disorders.
Höhmann
C F
CF
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Wilson
L
L
Coyle
J T
JT
D000344:Afferent Pathways / Q000166:cytology / Q000502:physiology*; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D003342:Corpus Striatum; D004525:Efferent Pathways / Q000166:cytology / Q000502:physiology*; D005260:Female; D006651:Histocytochemistry; D006735:Horseradish Peroxidase; D007267:Injections; D051379:Mice; D008807:Mice, Inbred BALB C; D009044:Motor Cortex / Q000166:cytology / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000502:physiology*; D011247:Pregnancy; D011712:Pyramidal Tracts / Q000166:cytology / Q000502:physiology; D013003:Somatosensory Cortex / Q000166:cytology / Q000502:physiology; D013788:Thalamus; D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate; D014909:Wheat Germ Agglutinins
D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate; D014909:Wheat Germ Agglutinins; D006735:Horseradish Peroxidase