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.
Crisp
Kevin M
KM
Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, Florida 33136, USA. crisp@stolaf.edu
Muller
Kenneth J
KJ
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*