Synaptic engineering: an ionic switch of behavior

RAYES, D.H.; PIRRI, J.; ALKEMA, M.

Congreso; XXVIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2013

The unraveling of the human brain connectivity map is considered as an essential step in the understanding how the brain controls behavior. However, the connectivity map does not carry information about the sign of synaptic connections. Is it possible to reverse the behavioral output of a circuit by changing the sign of a synapse? Does the sign of a synapse provide constraints to the development and the specification of a connectome? We address these questions using the neuronal circuit of the C. elegans escape response in which tyraminergic neurons coordinate the suppression of head movements with backward locomotion through the activation of tyramine-gated Cl- channel LGC-55. Amino acid substitution allowed us to change the selectivity of LGC-55 from Cl- to Na +. Localization of LGC-55 cation channel is indistinguishable from wild-type LGC-55. Exogenous tyramine induces neck muscle relaxation and backward locomotion in the wild-type animals, but induces neck muscle contraction and forward locomotion in transgenic animals that express the LGC-55 cation. Similarly, touch or optogentically induced release of endogenous tyramine triggers opposite behavioral responses in animals that express the LGC-55 cation vs LGC-55 anion channel. Our data show that changing the nature of a synapse within a neural circuit can reverse its behavioral output and indicate that the C. elegans connectome is established independent of the nature of synaptic activity or behavioral output.