THE EFFECT OF IONS AND 2ND MESSENGERS ON LONG-TERM POTENTIATION OF CHEMICAL TRANSMISSION IN AVIAN CILIARY GANGLIA

1 The effects of tetanic stimulation of the oculomotor nerve on transm ission through the avian ciliary ganglion have been determined by use of the amplitude of the compound action potential recorded in the cili ary nerve, in the presence of hexamethonium (300 mum), as a measure of synaptic efficacy. 2 Tetanic stimulation for 20 s at 30 Hz potentiate d the chemical phase of the compound action potential by at least 100% of its control level. This potentiation, reflecting an increase in sy naptic efficacy, decayed over two distinct time courses: firstly, a ra pid decay with a time constant in the order of minutes, and secondly, a slower decay, representing a smaller potentiation, with a time const ant in the order of an hour. The large increase in synaptic efficacy i s attributed to post-tetanic potentiation (PTP) whereas the smaller bu t longer lasting increase is attributed to long-term potentiation (LTP ). 3 Higher frequencies of tetanic stimulation gave increased PTP and LTP. 4 In order to test whether the influx of calcium ions into the ne rve terminal during the tetanus is likely to be involved in potentiati on, facilitation was measured during PTP and LTP. Facilitation was red uced to approximately zero during PTP but recovered to normal values a bout 15 min into LTP. A requirement for the induction of LTP was shown to be the presence of calcium in the bathing solution. However, block ing synaptic transmission with a high concentration of hexamethonium ( 3 mm) during the tetanic stimulation did not block the induction of LT P. 5 Application of the muscarinic inhibitor, atropine (2 mum), did no t affect the magnitude of PTP or LTP. 6 The activator of protein kinas e C, phorbol 12,13-dibutyrate (2 mum) potentiated synaptic transmissio n and reduced the potentiation due to PTP although it did not affect t hat due to LTP, but the inhibitor of this kinase, staurosporine (0.5 m um), partially blocked the appearance of LTP without affecting PTP aft er the tetanus. 7 An inhibitor of calmodulin, W-7 (5 mum), reversibly blocked the appearance of LTP significantly after a tetanus although t he size of PTP was not affected.8 The results presented here suggest t hat the initiation of LTP in the ciliary ganglion is due to an influx of calcium ions into the calyciform nerve terminal during the tetanus and that the mechanism for LTP involves a calcium-calmodulin-dependent process.