Selective serotonin reuptake inhibitor disrupts organization of thalamocortical somatosensory barrels during development.
To further investigate the role of the transiently expressed serotonin (5-HT) transporter (5-HTT) in the development of thalamic fibers projecting to cortical barrels and the potential developmental changes in neuronal circuitry caused by a selective serotonin reuptake inhibitor (SSRI), paroxetine (5 mg/kg, twice daily, s.c.) or saline was administered to rat pups from postnatal day 0 (P0) to P8. Pups were perfused on P8 for 5-HT immunostaining (-im) to confirm the 5-HT uptake blockade, and 5-HTT-im and phospholipase C-beta1 (PLC-beta1)-im to label the thalamic afferents to barrels and barrel cells respectively. Paroxetine treatment completely blocked 5-HT uptake into the thalamocortical fibers as indicated by the negative 5-HT-im in cortical barrel areas. Organization of thalamic afferents to barrels, indicated by 5-HTT-im or PLC-beta1, was altered in paroxetine-treated pups in the following manners: (1) segregation of thalamocortical fibers was partially disrupted and thalamocortical fibers corresponding to anterior snouts and row A mystacial vibrissae were fused; (2) sizes of the unfused thalamocortical fiber patches related to the long caudal vibrissae in rows B, C, D and E were significantly decreased without changes in the brain weights and cortical areas representing these vibrissae; and (3) thalamocortical fibers corresponding to C4 and D4 vibrissae tended to be closer to each other along the arc while the relative positions of thalamocortical fibers related to the rest of the vibrissae were normal. Our study demonstrated that 5-HTT plays an important role in the refinement, but not the formation, of barrel-like clusters of thalamocortical fibers and that the development of neural circuitry in rodent somatosensory cortex was affected by exposure to a SSRI during thalamocortical synaptic formation.
Xu
Yanling
Y
Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA.
Sari
Youssef
Y
Zhou
Feng C
FC
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009434:Neural Pathways / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D017374:Paroxetine / Q000494:pharmacology*; D054799:Phospholipase C beta; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013003:Somatosensory Cortex / Q000187:drug effects* / Q000378:metabolism; D013788:Thalamus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D014738:Vibrissae / Q000187:drug effects* / Q000254:growth & development / Q000294:innervation / Q000378:metabolism
D002352:Carrier Proteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017374:Paroxetine; D054799:Phospholipase C beta; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D010738:Type C Phospholipases; C493232:Slc6a4 protein, rat; C518035:Plcb1 protein, rat