Altered zincergic innervation of the developing primary somatosensory cortex in monoamine oxidase-A knockout mice.
Genetic inactivation of monoamine oxidase-A (MAO-A) significantly elevates levels of serotonin (5-HT) during early development and causes a disruption in the compartmented organization of thalamocortical axon terminals in layer 4 of the somatosensory cortex. In order to determine whether corticocortical innervation of the primary somatosensory cortex is also affected by this mutation, we examined the distribution of zinc-containing axon terminals (terminals known to originate from within the cortex) in the developing somatosensory cortex of MAO-A knockout mice, at postnatal days (PD) 3, 5, 6, 8, 10, 12, 15, 28, and 60. In layer 4 of wild-type mice, histochemical staining for zinc respected barrel-specific compartments at all ages beyond PD 5. By contrast, zinc staining in MAO-A knockout mice did not exhibit signs of barrel compartmentation at any age. Across cortical layers, substantial developmental changes in the distribution of zinc-containing terminals were observed in wild-type mice up until PD 12, at which time the mature lamina-specific pattern of zinc staining was achieved. Similar changes were observed in the somatosensory cortex of MAO-A knockout mice, except that its developmental time course was significantly compressed, with zincergic innervation achieving a mature appearance by PD 8. These results provide evidence that an excess of monoamines, most likely 5-HT, dramatically perturbs the columnar organization of intracortical zincergic afferents in layer 4 and significantly accelerates the appearance of a mature laminar pattern of zinc-containing corticocortical terminals.
Brown
Craig E
CE
Department of Psychology, University of Calgary, 2500 University Drive, NW, Calgary, Alberta T2N 1N4, Canada.
Seif
Isabelle
I
De Maeyer
Edward
E
Dyck
Richard H
RH
D000818:Animals; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008995:Monoamine Oxidase / Q000172:deficiency* / Q000235:genetics; D009154:Mutation; D017729:Presynaptic Terminals / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D013003:Somatosensory Cortex / Q000254:growth & development* / Q000502:physiology; D015032:Zinc / Q000378:metabolism*
D012701:Serotonin; D008995:Monoamine Oxidase; D015032:Zinc