A 3-synapse positive feedback loop regulates the excitability of an interneuron critical for sensitization in the leech.
Sensitization of reflexive shortening in the leech has been linked to serotonin (5-HT)-induced changes in the excitability of a single interneuron, the S cell. This neuron is necessary for sensitization and complete dishabituation of reflexive shortening, during which it contributes to the sensory-motor reflex. The S cell does not contain 5-HT, which is released primarily from the Retzius (R) cells, whose firing enhances S-cell excitability. Here, we show that the S cell excites the R cells, mainly via a fast disynaptic pathway in which the first synapse is the electrical junction between the S cell and the coupling interneurons, and the second synapse is a glutamatergic synapse of the coupling interneurons onto the R cells. The S cell-triggered excitatory postsynaptic potential in the R cell diminishes and nearly disappears in elevated concentrations of divalent cations because the coupling interneurons become inexcitable under these conditions. Serotonin released from the R cells feeds back on the S cell and increases its excitability by activating a 5-HT7-like receptor; 5-methoxytryptamine (5-MeOT; 10 microM) mimics the effects of 5-HT on S cell excitability, and effects of both 5-HT and 5-MeOT are blocked by pimozide (10 microM) and SB-269970 [(R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine-1-sulfonyl)phenol] (5 microM). This feedback loop may be critical for the full expression of sensitization of reflexive shortening.
Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, Florida 33136, USA. crisp@stolaf.edu
Kevin M
KM
Crisp
Kenneth J
KJ
Muller
D000818:Animals; D002478:Cells, Cultured; D004056:Differential Threshold / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D005246:Feedback / Q000502:physiology; D007395:Interneurons / Q000502:physiology*; D007865:Leeches / Q000502:physiology*; D009415:Nerve Net / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D012018:Reflex / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*