LOW-VOLTAGE-ACTIVATED CALCIUM CHANNELS IN THE LAMPREY LOCOMOTOR NETWORK - SIMULATION AND EXPERIMENT

To evaluate the role of low-voltage-activated (LVA) calcium channels i n the lamprey spinal locomotor network, a previous computer simulation model has been extended to include LVA calcium channels. It is also o f interest to explore the consequences of a LVA conductance for the el ectrical behavior of the single neuron. The LVA calcium channel was mo deled with voltage-dependent activation and inactivation using the m(3 )h form, following a Hodgkin-Huxley paradigm. Experimental data from l amprey neurons was used to provide parameter values of the single cell model. The presence of a LVA calcium conductance in the model could a ccount for the occurrence of a rebound depolarization in the simulatio n model. The influence of holding potential on the occurrence of a reb ound as well the latency at which it is elicited was investigated and compared with previous experiments. The probability of a rebound incre ased at a more depolarized holding potential and the latency was also reduced under these conditions. Furthermore, the effect of changing th e holding potential and the reversal potential of the calcium dependen t potassium conductance were tested to determine under which condition s several rebound spikes could be elicited after a single inhibitory p ulse in the simulation model. A reduction of the slow afterhyperpolari zation (sAHP) after the action potential reduced the tendency for a tr ain of rebound spikes. The experimental effects of gamma-aminobutyric acid-B (GABA(B)) receptor activation were simulated by reducing the ma ximal LVA calcium conductance. A reduced tendency for rebound firing a nd a slower rising phase with sinusoidal current stimulation was obser ved, in accordance with earlier experiments. The effect of reducing th e slow afterhyperpolarization and reducing the LVA calcium current was tested experimentally in the lamprey spinal cord, during N-methyl-D-a spartate (NMDA)-induced fictive locomotion. The reduction of burst fre quency was more pronounced with GABA(B) agonists than with apamin (inh ibitor of K-(Ca) current) when using high NMDA concentration (high bur st frequency). The burst frequency increased after the addition of a L VA calcium current to the simulated segmental network, due to a faster recovery during the inhibitory phase as the activity switches between the sides. This result is consistent with earlier experimental findin gs because GABA(B) receptor agonists reduce the locomotor frequency. T hese results taken together suggest that the LVA calcium chancels cont ribute to a larger degree with respect to the burst frequency regulati on than the sAHP mechanism at higher burst frequencies. The range in w hich a regular burst pattern can be simulated is extended in the lower range by the addition of LVA calcium channels, which leads to more st able activity at low locomotor frequencies. We conclude that the prese nt model can account for rebound firing and trains of rebound spikes i n lamprey neurons. The effects of GABA(B) receptor activation on the n etwork level is consistent with a reduction of the calcium current thr ough LVA calcium channels even though GABA(B) receptor activation will affect the sAHP indirectly and also presynaptic inhibition.