Serotonin targets inhibitory synapses to induce modulation of network functions.
The cellular effects of serotonin (5-HT), a neuromodulator with widespread influences in the central nervous system, have been investigated. Despite detailed knowledge about the molecular biology of cellular signalling, it is not possible to anticipate the responses of neuronal networks to a global action of 5-HT. Heterogeneous expression of various subtypes of serotonin receptors (5-HTR) in a variety of neurons differently equipped with cell-specific transmitter receptors and ion channel assemblies can provoke diverse cellular reactions resulting in various forms of network adjustment and, hence, motor behaviour. Using the respiratory network as a model for reciprocal synaptic inhibition, we demonstrate that 5-HT(1A)R modulation primarily affects inhibition through glycinergic synapses. Potentiation of glycinergic inhibition of both excitatory and inhibitory neurons induces a functional reorganization of the network leading to a characteristic change of motor output. The changes in network operation are robust and help to overcome opiate-induced respiratory depression. Hence, 5-HT(1A)R activation stabilizes the rhythmicity of breathing during opiate medication of pain.
Manzke
Till
T
Department of Neuro- and Sensory Physiology, University of Göttingen, , 37073 Göttingen, Germany.
Dutschmann
Mathias
M
Schlaf
Gerald
G
Mörschel
Michael
M
Koch
Uwe R
UR
Ponimaskin
Evgeni
E
Bidon
Olivier
O
Lalley
Peter M
PM
Richter
Diethelm W
DW
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism*; D002065:Buspirone / Q000494:pharmacology; D002415:Cats; D017931:DNA Primers / Q000235:genetics; D004525:Efferent Pathways / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009415:Nerve Net / Q000469:parasitology*; D010507:Periodicity; D010636:Phenols / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D015656:Respiratory Mechanics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D010636:Phenols; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; C404922:SB 269970; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002065:Buspirone