EFFECTS OF MONOAMINE-OXIDASE A INHIBITION ON BARREL FORMATION IN THE MOUSE SOMATOSENSORY CORTEX - DETERMINATION OF A SENSITIVE DEVELOPMENTAL PERIOD

Genetic inactivation of monoamine oxidase A (MAOA) in C3H/HeJ mice cau ses a complete absence of barrels in the somatosensory cortex, and sim ilar alterations are caused by pharmacological inhibition of MAOA in w ild type mice. To determine when and bow MAOA inhibition affects the d evelopment of the barrel field, the MAOA inhibitor clorgyline was admi nistered to mice of the outbred strain OF1 for various time periods be tween embryonic day 15 (E15) and postnatal day 7 (P7), and the barrel fields were analyzed with cytochrome oxidase and Nissl stains in P10 a nd adult mice. High-pressure liquid chromatography measures of brain s erotonin (5-HT) showed three-to eightfold increases during the periods of clorgyline administration. Perinatal mortality was increased and w eight gain was slowed between P3 and P6. Clorgyline treatments from E1 5 to P7 or from P0 to P7 disrupted the formation of barrels in the ant erior snout representation and in parts of the posteromedial barrel su bfield (PMBSF). Treatments from P0 to P4 caused similar although less severe barrel field alterations. Clorgyline treatments only during emb ryonic life or starting on P4 caused no detectable abnormalities. In c ases with barrel field alterations, a rostral-to-caudal gradient of ch anges was noted: Rostral barrels of the PMBSF were most frequently fus ed and displayed an increased size tangentially. Thus, MAOA inhibition resulting in increased brain levels of 5-HT affects barrel developmen t during the entire first postnatal week, with a sensitive period betw een P0 and P4. The rostral-to-caudal gradient of changes in the barrel field parallels known developmental gradients in the sensory peripher y and in the maturation thalamocortical afferents. The observed barrel fusions could correspond to a default in the initial segregation of t halamic fibers or to a continued, exuberant growth of these fibers tha t overrides the tangential domain that is normally devoted to individu al whiskers. (C) 1998 Wiley-Liss, Inc.