Modeling of substance P and 5-HT induced synaptic plasticity in the lamprey spinal CPG: Consequences for network pattern generation

Consequences of synaptic plasticity in the lamprey spinal CPG are analyzed by means of simulations. This is motivated by the effects substance P (a ta chykinin) and serotonin (5-hydroxytryptamin; 5-HT) have on synaptic transmi ssion in the locomotor network. Activity-dependent synaptic depression and potentiation have recently been shown experimentally using paired intracell ular recordings. Although normally activity-dependent plasticity presumably does not contribute to the patterning of network activity, this changes in the presence of the neuromodulators substance P and 5-HT, which evoke sign ificant plasticity. Substance P can induce a faster and larger depression o f inhibitory connections but potentiation of excitatory inputs, whereas 5-H T induces facilitation of both inhibitory and excitatory inputs. Changes in the amplitude of the first postsynaptic potential are also seen. These cha nges could thus be a potential mechanism underlying the modulatory role the se substances have on the rhythmic network activity. The aim of the present study has been to implement the activity dependent s ynaptic depression and facilitation induced by substance P and 5-HT into tw o alternative models of the lamprey spinal locomotor network, one relying o n reciprocal inhibition for bursting and one in which each hemicord is capa ble of oscillations. The consequences of the plasticity of inhibitory and e xcitatory connections are then explored on the network level. In the intact spinal cord, tachykinins and 5-HT, which can be endogenously released, increase and decrease the frequency of the alternating left-right burst pattern, respectively. The frequency decreasing effect of 5-HT has p reviously been explained based on its conductance decreasing effect on K un derlying the postspike afterhyperpolarization (AHP). The present simulation s show that short-term synaptic plasticity may have strong effects on frequ ency regulation in the lamprey spinal CPG. In the network model relying on reciprocal inhibition, the observed effects substance P and 5-HT have on ne twork behavior (i.e., a frequency increase and decrease respectively) can t o a substantial part be explained by their effects on the total extent and time dynamics of synaptic depression and facilitation. The cellular effects of these substances will in the 5-HT case further contribute to its networ k effect.