PT  - JOURNAL ARTICLE
AU  - Kevin M. Crisp
AU  - Kenneth J. Muller
TI  - A 3-Synapse Positive Feedback Loop Regulates the Excitability of an Interneuron Critical for Sensitization in the Leech
AID  - 10.1523/JNEUROSCI.3056-05.2006
DP  - 2006 Mar 29
TA  - The Journal of Neuroscience
PG  - 3524--3531
VI  - 26
IP  - 13
4099  - http://www.jneurosci.org/content/26/13/3524.short
4100  - http://www.jneurosci.org/content/26/13/3524.full
SO  - J. Neurosci.2006 Mar 29; 26
AB  - 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 μm) mimics the effects of 5-HT on S cell excitability, and effects of both 5-HT and 5-MeOT are blocked by pimozide (10 μm) and SB-269970 [(R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine-1-sulfonyl)phenol] (5 μm). This feedback loop may be critical for the full expression of sensitization of reflexive shortening.