Neonatal 5,7-DHT lesions cause sex-specific changes in mouse cortical morphogenesis.
Both monoaminergic and cholinergic afferent projections to the neocortex putatively modulate cortical morphogenesis and plasticity. Previously we showed that neonatal electrolytic lesions of the cholinergic nucleus basalis magnocellularis (nBM) projections to the neocortex result in significant decreases of cortical layer width that correlate with cognitive alterations. Such electrolytic lesions, performed for lack of a selective neurotoxin in mice, may affect mono-aminergic fibers of passage. Here, we investigate the effects of neonatal 5,7 dihydroxytryptamine (5,7-DHT) focal injections into the nBM region on cortical laminar morphology in adult male and female mice. 5,7-DHT lesions on the first postnatal day resulted in significant cortical depletion of both serotonin and norepinephrine that attenuated with age. Generally, cortical layer widths increased in response to the lesion; the effects were layer, region, and sex specific. Previous reports from our laboratories described long-term behavioral alterations after comparable focal, neonatal 5,7-DHT lesions. The studies described here provide an anatomical basis for such behavioral alterations. Our data suggest that monoaminergic and cholinergic projections to the cortex may have opposite effects on the developing cortical neuropil. Jointly, our morphological and behavioral findings may have important implications for a variety of developmental disorders in humans and provide some insights into sex differences in the penetrance of these disorders.
Hohmann
C F
CF
Department of Biology, Morgan State University, Cold Spring Lane and Hillen Rd., Baltimore, MD 21251, USA. chohmann@morgan.edu
Richardson
C
C
Pitts
E
E
Berger-Sweeney
J
J
D015116:5,7-Dihydroxytryptamine / Q000633:toxicity; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D020532:Basal Nucleus of Meynert / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000254:growth & development*; D005260:Female; D007839:Functional Laterality; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009024:Morphogenesis; D009638:Norepinephrine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D012727:Sex Characteristics; D013003:Somatosensory Cortex / Q000254:growth & development
D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D009638:Norepinephrine