LONG-TERM POTENTIATION OF GLYCINERGIC INHIBITORY SYNAPTIC TRANSMISSION. ODA, Yoichi, Stephane CHARPIER, Yusuke MURAYAMA, Chieko SUMA, and Henri KORN. Laboratory of Cellular and Molecular Neurobiology, INSERM U261, Institut Pasteur, 25, rue du Dr Roux, 75724 PARIS CEDEX 15, France and Department of Biophysical Engineering, Faculty of Engineering Science, Osaka University, Machikaneyama 1-3, Toyonaka, Osaka 560, Japan.
APStracts 2:0129N, 1995.
SUMMARY AND CONCLUSIONS
1. Tetanizing protocols were used to test whether glycinergic inhibition undergoes long-term plasticity in vivo. For this purpose, we studied the inhibition evoked disynaptically in the Teleost Mauthner (M-) cell by stimulation of the posterior branch of the contralateral eighth nerve (VIII n.). The advantage of this experimental design is that the inhibition, which is mediated by identified second order commissural interneurons is not contaminated by parallel excitation. 2. The VIII n. evoked inhibitory postsynaptic potentials (IPSPs) which are generated at the level of the soma are depolarizing in Cl- loaded M-cells. Following VIII n. tetanization, these IPSPs exhibited potentiation lasting more than 30 min in 23 out of 31 cells. The maximum enhancement measured 5 to 10 min after the onset of the tetanization averaged 100 19 % (SEM). In contrast, the non "tetanized" collateral IPSP induced by antidromic stimulation of the M-axon did not increase significantly suggesting synaptic specificity of the potentiation. 3. Single electrode voltage clamp studies of Cl- loaded M-cells indicated that this plasticity is due to an increased synaptic conductance which occurs without obvious modifications of the kinetics or voltage dependence of the inhibitory postsynaptic currents (IPSCs). 4. The synaptic conductance and its changes during potentiation were quantified by measuring the inhibitory shunt of the antidromic spike, while recording with potassium acetate (KAc) filled electrodes. For this purpose the ratio, r', of the inhibitory to resting membrane conductances (Gipsp/Gm) was calculated using the expression (V/V')-1 where V and V' are the amplitudes of the control and the test antidromic spikes, respectively. This ratio was called fractional conductance. Measured at the peak of the expected VIII n. evoked IPSP, r' increased by 114 18 % (n=46). Again the collateral inhibitory conductance was not modified. 5. Since there are two synapses in the inhibitory pathway, it became important to determine if modifications of the second order inhibitory junctions contribute to the overall potentiation. Several experimental procedures were used for this purpose. 6. The input-output relationship at the inhibitory synapses was determined by comparing the size of the presynaptic volley and r'. The former was recorded intra- or extracellularly as a monophasic positive potential, the so-called extrinsic hyperpolarizing potential (EHP) which increases in parallel with the strength of VIII n. stimulation. In 12 experiments where the presynaptic volley was unaffected by the tetanization, suggesting lack of involvement of the first relay, r' nevertheless increased in amplitude by 79{CARSPECIAUX 177 \f "Symbol"}14%. 7. In another 8 experiments, the volley was increased by the conditioning protocol, indicating potentiation at the first order excitatory relay. When the input-output function of the inhibitory synapses was examined over a wide range of test stimulus intensities, its slope was 50 20 % steeper at 30 min post- tetanization. This enhancement could occur when only a few commissural interneurons were tetanized by low intensity trains. 8. Direct evidence for plasticity of the inhibitory synapses was obtained with paired recordings from identified commissural interneurons and Cl- loaded M-cells. Stability of Cl- loading was monitored using the amplitude of the collateral IPSP (Vcoll) as a control. Eight of 23 pairs exhibited potentiation, with an average IPSP increase of 70 20 %, the longest recording session lasting 24 min after tetanization. 9. Taken together these results demonstrate that inhibitory synapses undergo a form of plasticity comparable to that termed long-term potentiation (LTP) at excitatory junctions. 10. Evidence suggests that a minimum level of M-cell cytoplasmic Ca2+ is necessary for the induction of the inhibitory LTP : depolarizations applied to the M-cell in conjunction with repeated test stimulations of the contralateral VIII n. resulted in a persistent potentiation. This observation is consistent with an earlier finding that postsynaptic injection of a Ca2+ chelator blocks induction of this potentiation. 11. Although quantal analysis was not systematically performed, results obtained using the coefficient of variation and constraint deconvolution methods were in close agreement and suggested that the inhibitory LTP is mainly expressed presynaptically. 12. The functional meaning of this form of plasticity is discussed in the context of its role in the control and adaptability of reflex activities rather than within the more conventional scheme of learning and memory. Consideration of network design, properties of the M-cell's afferent inputs and factors involved in acoustic localization lead to the suggestions that inhibitory LTP contribute to the direction and orientation of the sound evoked startle response triggered by the M-cell. 

Received 2 December 1994; accepted in final form 12 April 1995.
APS Manuscript Number J756-4.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  2 May 1995.