Spatial segregation of excitatory and inhibitory effects of 5-HT on

35 36 Altering neuronal membrane properties, including input resistance, is a key 37 modulatory mechanism for changing neural activity patterns. The effect of membrane 38 currents generated by either synaptic or voltage-dependent channels directly depends on 39 neuron input resistance. We found that local application of serotonin to different regions of 40 identified motor neurons of the postural/walking network of isolated crayfish produced 41 different changes in input resistance. Puff-applied 5-HT in the periphery of the initial 42 segment produced exclusively inhibitory responses. In contrast, when 5-HT was 43 puff-applied on the central arbor of the same Dep MN, exclusively depolarizing responses 44 were obtained. Both inhibitory and excitatory responses were direct because they 45 persisted in low calcium saline. We found numerous close appositions between 5-HT 46 immunoreactive processes and the initial segment of dextran rhodamine-filled depressor 47 (Dep) MNs. In contrast, almost no close apposition sites were found in Dep MN arbor. It 48 seems that the 5-HT controls the level of excitability of postural network MNs by two 49 mechanisms acting at two different sites: inhibitory responses (consistent with an action 50 involving opening of K channels) occur in the initial segment region and may involve 51 classical synaptic transmission, while depolarizing responses (consistent with an action 52 involving closing of K channels) occur on MN branches via apparent paracrine effects. 53