Modulation of Intrinsic Spiking in Spinal Cord

33 34 The vertebrate spinal cord is equipped with a number of neuronal networks that 35 underlie repetitive patterns of behavior like locomotion. Activity in such networks 36 is mediated by intrinsic cellular properties as well as by synaptic coupling. In this 37 study, we focused on the modulation of the intrinsic activity by 5-HT and the 38 cholinergic agonist muscarine in spinal cord cultures (E14 rats). We investigated 39 theses cultures (slices and dissociated cells) at the network level using 40 multielectrode arrays (MEAs) and at the cellular level using whole cell patch 41 clamp. All cultures showed bursting network activity and intrinsic activity when 42 GABA, glycine and glutamate transmission was blocked. Using MEAs, we 43 observed an increase of the intrinsic activity in the ventral part of the slices with 44 5-HT and muscarine. In single cell recordings we found that 43% and 35% of the 45 cells that were silent in the absence of fast synaptic activity were 46 transformed into intrinsically spiking cells by 5-HT and muscarine respectively. 47 We tested the hypothesis that these neuromodulators act via modulation of the 48 persistent sodium currents INaP in these neurons. We found that 5-HT increased 49 three fold the amplitude of INaP specifically in the non-intrinsically spiking cells 50 and thus switched these cells into intrinsically spiking cells via activation of 5-HT2 51 receptor and the PLC pathway. In contrast, the effect of muscarine on non52 intrinsically spiking neurons seems to be independent of INaP. We conclude from 53 these findings that serotoninergic and cholinergic modulation can turn silent into 54