title: Modeling of substance P and 5-HT induced synaptic plasticity in the lamprey spinal CPG: consequences for network pattern generation.
abstract: Consequences of synaptic plasticity in the lamprey spinal CPG are analyzed by means of simulations. This is motivated by the effects substance P (a tachykinin) and serotonin (5-hydroxytryptamin; 5-HT) have on synaptic transmission in the locomotor network. Activity-dependent synaptic depression and potentiation have recently been shown experimentally using paired intracellular 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 significant plasticity. Substance P can induce a faster and larger depression of inhibitory connections but potentiation of excitatory inputs, whereas 5-HT induces facilitation of both inhibitory and excitatory inputs. Changes in the amplitude of the first postsynaptic potential are also seen. These changes could thus be a potential mechanism underlying the modulatory role these substances have on the rhythmic network activity. The aim of the present study has been to implement the activity dependent synaptic depression and facilitation induced by substance P and 5-HT into two alternative models of the lamprey spinal locomotor network, one relying on reciprocal inhibition for bursting and one in which each hemicord is capable of oscillations. The consequences of the plasticity of inhibitory and excitatory 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 previously been explained based on its conductance decreasing effect on K(Ca) underlying the postspike afterhyperpolarization (AHP). The present simulations show that short-term synaptic plasticity may have strong effects on frequency regulation in the lamprey spinal CPG. In the network model relying on reciprocal inhibition, the observed effects substance P and 5-HT have on network behavior (i.e., a frequency increase and decrease respectively) can to 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 network effect.
authors.affiliation: Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institute, SE-171 77 Stockholm, Sweden. akoslov@nada.kth.se
authors.forename: A
authors.initials: A
authors.lastname: Kozlov
authors.forename: J H
authors.initials: JH
authors.lastname: Kotaleski
authors.forename: E
authors.initials: E
authors.lastname: Aurell
authors.forename: S
authors.initials: S
authors.lastname: Grillner
authors.forename: A
authors.initials: A
authors.lastname: Lansner
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D007798:Lampreys / Q000033:anatomy & histology / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D023421:Models, Animal; D008959:Models, Neurological; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009415:Nerve Net / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D016571:Neural Networks, Computer; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D018091:Receptors, AMPA / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D012701:Serotonin; D013373:Substance P