Synaptic engineering: An ionic switch of behavior

PIRRI J; RAYES D; ALKEMA M

New York, USA

Congreso; Neuronal Circuits Meeting. Cold Spring Harbor.. Cold Spring Harbor, NY, USA; 2012

Cold Spring Harbor Laboratories

The unraveling of the human connectome is considered by many as an essential step in understanding how the brain controls behavior. However, the neural connectivity map does not carry information about the nature of synaptic connections. Whether a synapse is excitatory or inhibitory within a neural circuit should drastically change the behavioral output of the circuit. Is it possible to change the behavioral output of a neural circuit by changing the nature of a synapse? Does the nature of a synapse provide constraints to the wiring, the specification, and behavioral output of a connectome? We have addressed this question in the only currently known connectome, that of the nematode C. elegans. C. elegans has a single pair of tyraminergic neurons that coordinate the suppression of head movements with backward locomotion in the animal´s touch response. Touch-induced tyramine release leads to the activation of an inhibitory postsynaptic receptor, the tyramine-gated chloride channel LGC-55. LGC-55 is a member of the ligand-gated ion channel family, whose ion selectivity is determined by the intracellular loop between transmembrane domains M1 and M2. We selectively mutated residues of this loop in LGC-55 to a channel selective for Na+ and K+. A fluorescently tagged LGC-55 cation channel localizes opposite tyramine release sites indistinguishable from the wild-type LGC-55 anion channel. Touch or optogenetically induced tyramine release triggers opposite behavioral responses in animals that express the LGC-55 cation vs LGC-55 anion channel. Tyramine induces neck muscle relaxation and backward locomotion in wild-type LGC-55 anion animals, but induces neck muscle contraction and forward locomotion in transgenic animals that express the LGC-55 cation channel. Our data show that changing the nature of a synapse within a neural circuit can reverse its behavioral output and indicate that the connectome is established independent of the nature of synaptic activity or behavioral output.