EFFECTS OF 5-HT ON THALAMOCORTICAL SYNAPTIC TRANSMISSION IN THE DEVELOPING RAT

1. Recent immunocytochemical and receptor binding data have demonstrat ed a transient somatotopic patterning of serotonin (5-HT)-immunoreacti ve fibers in the primary somatosensory cortex of developing rats and a transient expression of 5-HT1B receptors on thalamocortical axons fro m the ventral posteromedial thalamic nucleus (VPM). 2. These results s uggest that 5-HT should strongly modulate thalamocortical synaptic tra nsmission for a limited time during postnatal development. This hypoth esis was tested in intracellular recording experiments carried out in thalamocortical slice preparations that included VPM, the thalamic rad iations, and the primary somatosensory cortex. Effects of 5-HT and ana logues were monitored on membrane potentials and input resistances of cortical neurons and on the amplitude of the synaptic potentials evoke d in them by stimulation of VPM. 3. Results obtained from cortical neu rons in slices taken from rats during the first 2 wk of life indicated that 5-HT strongly inhibited the VPM-evoked excitatory postsynaptic p otential (EPSP) recorded from cortical neurons in a dose-dependent man ner. In contrast, 5-HT had no significant effects on membrane potentia l, input resistance, or depolarizations induced by direct application of glutamic acid to cortical cells. 4. The effects of 5-HT were mimick ed by the 5-HT1B receptor agonists 1-[3-(trifluoromethyl)phenyl]-piper azine (TFMPP) and trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo- [ 1,2-a]quinoxaline maleate and antagonized by the 5-HT1B receptor antag onist (-)-pindolol. The 5-HT1A agonist [(+/-)8-hydroxydipropylaminotet ralin HBr] (8-OH-DPAT) had less effect on the VPM-elicited EPSP, and t he effects of 5-HT upon this response were generally not antagonized b y either 1-(2-methoxyphenyl)-4-[4-(2-phthalimmido)butyl] -piperazine H Br (a 5HT(1A) antagonist) or ketanserine (a 5-HT2 antagonist) or spipe rone (a 5-HT1A and 2 antagonist). 5. The ability of 5-HT to inhibit th e VPM-evoked EPSP in cortical neurons was significantly reduced in sli ces from animals >2 wk of age. The effectiveness of TFMPP in such anim als was even more attenuated than that of 5-HT, and the effectiveness of 8-OH-DPAT was unchanged with age. These results are consistent with the disappearance of 5-HT1B receptors from thalamocortical axons afte r the second postnatal week and the maintenance of 5-HT1A receptors on some neurons. 6. All of the results obtained in this study are consis tent with the conclusion that 5-HT has a profound, but developmentally transient, presynaptic inhibitory effect upon thalamocortical transmi ssion in the rat's somatosensory cortex.