Neuronal Adaptations to Changes in the Social Dominance Status of Crayfish

The effect of superfused serotonin (5-HT; 50 mM) on the synaptic responses of the lateral giant (LG) interneuron in crayfish was found to depend on the social status of the animal. In socially isolated animals, 5-HT persistently increased the response of LG to sensory nerve shock. After social isolates were paired in a small cage, they fought and determined their dominant and subordinate status. After 12 d of pairing, 5-HT reversibly inhibited the response of LG in the social subordinate and reversibly increased the response of LG in the social dominant crayfish. The effect of 5-HT changed approximately linearly from response enhancement to inhibition in the new subordinate over the 12 d of pairing. If, after 12 d pairing, the subordinate was reisolated for 8 d, the response enhancement was restored. If the subordinate, instead, was paired with another subordinate and became dominant in this new pair, the inhibitory effect of 5-HT changed to an enhancing effect over the next 12 d of pairing. If, however, two dominant crayfish were paired and one became subordinate, the enhancing effect of 5-HT persisted in the new subordinate even after 38 d pairing. These different effects of serotonin result from the action of two or more molecular receptors for serotonin. A vertebrate 5-HT1 agonist had no effect on social isolates but reversibly inhibited the response of LG in both dominant and subordinate crayfish. The inhibitory effects of the agonist developed approximately linearly over the first 12 d of pairing. A vertebrate 5-HT2 agonist persistently increased the response of LG in isolate crayfish and reversibly increased the response of the cell in dominant and subordinate crayfish. Finally, although neurons that might mediate these effects of superfused 5-HT are unknown, one pair of 5-HT-immunoreactive neurons appears to contact the LG axon and initial axon segment in each abdominal ganglion in its projection caudally from the thorax

Dual and Opposing Modulatory Effects of Serotonin on Crayfish Lateral Giant Escape Command Neurons

Serotonin modulates afferent synaptic transmission to the lateral giant neurons of crayfish, which are command neurons for escape behavior. Low concentrations, or high concentrations reached gradually, are facilitatory, whereas high concentrations reached rapidly are inhibitory. The modulatory effects rapidly reverse after brief periods of application, whereas longer periods of application are followed by facilitation that persists for hours. These effects of serotonin can be reproduced by models that involve multiple interacting intracellular signaling systems that are each stimulated by serotonin. The dependence of the neuromodulatory effect on dose, rate, and duration of modulator application may be relevant to understanding the effects of natural neuromodulation on behavior and cognition and to the design of drug therapies

Fak56 functions downstream of integrin alphaPS3betanu and suppresses MAPK activation in neuromuscular junction growth

Background: Focal adhesion kinase (FAK) functions in cell migration and signaling through activation of the mitogen-activated protein kinase (MAPK) signaling cascade. Neuronal function of FAK has been suggested to control axonal branching; however, the underlying mechanism in this process is not clear. Results: We have generated mutants for the Drosophila FAK gene, Fak56. Null Fak56 mutants display overgrowth of larval neuromuscular junctions (NMJs). Localization of phospho-FAK and rescue experiments suggest that Fak56 is required in presynapses to restrict NMJ growth. Genetic analyses imply that FAK mediates the signaling pathway of the integrin αPS3βν heterodimer and functions redundantly with Src. At NMJs, Fak56 downregulates ERK activity, as shown by diphospho-ERK accumulation in Fak56 mutants, and suppression of Fak56 mutant NMJ phenotypes by reducing ERK activity. Conclusion: We conclude that Fak56 is required to restrict NMJ growth during NMJ development. Fak56 mediates an extracellular signal through the integrin receptor. Unlike its conventional role in activating MAPK/ERK, Fak56 suppresses ERK activation in this process. These results suggest that Fak56 mediates a specific neuronal signaling pathway distinct from that in other cellular processes