The effects of neurotransmitters on the integrative properties of spinal neurons in the lamprey

1. The integrative behavior of lamprey central neurons was analyzed by white noise frequency domain methods and simulated with a minimal, non-linear neuronal model consisting of two voltage-dependent processes: (i) a depolarizing inwardly directed conductance carrying calcium and monovalent ions and (ii) a repolarizing outwardly directly conductance representing a generalized potassium conductance. In addition to normal properties, the effects of neurotransmitters were interpreted with the model. Specifically, N-methyl-D-aspartate (NMDA)-induced properties were simulated under conditions where the intrinsic voltage dependence of the potassium channels was constrained by properties of lamprey neurons. However, the NMDA channel kinetics were fixed by the single-channel properties of other neurons. The effects of focally applied neurotransmitters on the membrane properties of intact spinal cord neurons were quantitatively described with a reduced neuronal model that was also used to simulate transmitter-induced responses. In addition, transmitters were also released synaptically by KCl depolarization of projecting neurons. 2. Both synaptically released transmitters and focally applied putative excitatory or inhibitory transmitters directly applied to the spinal cord generally resulted in a decrease in the magnitude of the impedance function that was modeled by a decrease in membrane resistance (shunting effect). 3. Local application of the inhibitory neurotransmitters glycine or gamma-aminobutyric acid (GABA) led to small voltage responses when recorded near the resting potential. However, large decreases in the magnitude of the impedance function were observed in both current-clamp or voltage-clamp recording modes. 4. The excitatory amino acids quisqualate, kainate and glutamate evoked depolarizations in current clamp that activated intrinsic voltage-dependent conductances and obscured the direct effects of the transmitters. Under voltage-clamp conditions these transmitters caused a small decrease in the impedance magnitude that could be modeled by a shunt. 5. In contrast to the other excitatory amino acids, NMDA elicited large increases, rather than decreases, in both the magnitude and the phase lag of the impedance function. These changes were modeled by a negative conductance (a voltage-dependent conductance that produces an inward current). 6. The reduced neuron model provides an experimentally based description of the highly oscillatory and non-linear responses observed during NMDA activation of the spinal neurons involved in the pattern generation of locomotion. Simulations of sustained oscillatory behaviors consistent with experimental observations were carried out to illustrate the NMDA-induced integrative properties of central neurons.(ABSTRACT TRUNCATED AT 400 WORDS)