European Journal zyxwvutsrqpon of Neuroscience, Vol. zyxwvutsrqp 7, pp. 1097-1106, 1995 zyxwvuts @ European Neuroscience Association Long-lasting Potentiation of a Direct Central Connection between Identified Motor Neurons in the Locust zy David Parker Department of Zoology, Cambridge University, Downing Street, Cambridge, CB2 3EJ, UK Keywords: potentiation, locust, motor neuron, synapse, plasticity Abstract The plasticity of the direct central connection between the fast extensor and the posterior fast flexor tibiae motor neurons in the locust zyxwvutsrq (Schistocerca gregaria) metathoracic ganglion was studied. An action potential in the fast extensor results in a monosynaptic excitatory postsynaptic potential (EPSP) in the flexor motor neuron. Antidromic stimulation of the fast extensor at 100 Hz for 3.5 s resulted in a long-lasting potentiation of the EPSP amplitude. The potentiation was not dependent on feedback caused by movement of the tibia, and was associated with an increase in the input resistance of the flexor motor neuron. The potentiation was heterosynaptic, and was not affected by bath application of the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovaleric acid. The potentiation was voltage dependent, as hyperpolarizing the flexor motor neuron during the stimulation blocked the development of the potentiation whereas depolarizing the flexor in the absence of presynaptic activity caused potentiation of subsequent fast extensor-evoked EPSPs. The depolarization-induced potentiation was calcium dependent. Antidromic stimulation of the fast extensor at 100 Hz for 3.5 s also caused modulation of the presynaptic action potential. The spike duration was increased and the amplitude of the afterhyperpolarization reduced. These effects were dependent on movement of the tibia. Bath application of the 5-hydroxytryptamine(5-HT) receptor antagonist ketanserin blocked the changes in the presynaptic spike. The modulation was probably due to the release of 5-HT from proprioceptive afferents that monitor movement of the tibia about the femur. The modulation of the presynaptic action potential increases transmitter release onto the flexor motor neurons, and this acts in synergy with the postsynaptic modulation to potentiate the connection. Introduction zyxwvutsrqpo Alterations in behaviour often require changes in the output of neural circuits. This can be achieved by alterations in the intrinsic membrane properties of neurons and their synaptic connections, either through the release of neuromodulators, or by plasticity of the synaptic connections. This paper examines a synapse between identified motor neurons in the locust that shows postsynaptic potentiation and presynaptic modulation as a result of brief high frequency stimulation of the presynaptic neuron. Most forms of synaptic plasticity are associated with modulation of transmitter release from the presynaptic neuron. For example, post- tetanic potentiation is associated with an increase in transmitter release, possibly as a result of residual sodium or calcium ions in the terminals (Katz and Miledi, 1970; Rahaminoff et al., 1980), and synaptic depression is associated with a reduction of transmitter release, either by reducing a presynaptic calcium current (Klein et al., 1980; Parker, 1993), or by depletion of releasable transmitter stores (Liley and North, 1953). Long-term potentiation (LTP), however, is a long-lasting form of synaptic potentiation that has its locus for induction in the postsynaptic neuron (see Bliss and Collingridge, 1993). LTP is characterized by a long-lasting increase in synaptic strength following brief high frequency stimulation (Bliss and L0m0, 1973), which is dependent for its induction on postsynaptic depolariza- tion (Kelso et al., 1986; Keller et al., 1991), and on calcium entry (MacDermott et al., 1986). Although the induction of LTP is understood, the mechanism responsible for maintenance is uncertain, suggested mechanisms including an increase in transmitter release from the presynaptic neuron (Bliss et al., 1990; Malinow and Tsien, 1990) and an increase in postsynaptic response (Crick, 1982; Asztely et al., 1992; Yamamoto et al., 1993). Instead of purely presynaptic or postsynaptic maintenance, quanta1 analysis has shown that LTP in the same region of the hippocampus can be maintained presynaptically or postsynaptically, or by a mixture of both mechanisms (Kullman and Nicoll, 1992). depending on the initial rate of transmitter release (Hannay et al., 1993). In the locust metathoracic ganglion, the fast extensor tibiae motor neuron (FETi) makes direct central connections with a posterior group of flexor motor neurons (Burrows et al., 1989). This group has a slow, a fast and an intermediate flexor motor neuron. The experiments described in this paper examine a relatively long- lasting form of synaptic potentiation at the direct central connection between FETi and the posterior fast flexor tibiae motor neuron (PFFl). Correspondence to: D. Parker, Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institute, S- 17 1 17, Stockholm, Sweden Received 18 August, 1994, revised I Decembes 1994, accepted 13 Decembec 1994