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Inhibition is critical for the proper functioning of neural circuits. Crayfish present

a unique opportunity for the study of inhibition. Crustaceans have been used extensively as model organisms, and many important neuroscientific phenomena were originally described in crayfish or other crustaceans. Their escape responses, mediated by giant fibers, have received particular attention. The lateral giant system has been mapped out in great detail, and every synapse between the receptors that stimulate it to the muscles it recruits is known. Quite surprisingly, despite this extensive knowledge of the excitatory portions of the circuit, its inhibitors are still poorly understood. The lateral giant interneuron is a particularly good target in which to study inhibition, as it receives three unique types of inhibition. Its firing causes a rapid autoinhibition of the neuron, its general excitability is modulated by tonic inhibition, and its selectivity to sudden, phasic stimuli is partially mediated by sensory-evoked inhibition. While the existence and very basic characterization of these forms of inhibition have been described, the mechanisms and details of all three remain elusive. Here I present data which aids substantially in our understanding of these inhibitory systems. I show that the lateral giant’s autoinhibition is mediated by both GABA and glutamate, and that the axon of lateral giant neuron responds to these inhibitory neurotransmitters. I also pharmacologically characterize the inhibitory inputs evoked by its sensory afferents, and show that the neuron is sensitive to THIP, a compound which is selective for receptor subtypes that mediate tonic inhibition. In addition, I utilize alcohol exposure to uncover these mechanisms, allowing it to be used to interpret the recently discovered social modulation of alcohol’s effect that is seen in crayfish, and aiding in our understanding of alcohol’s interplay with cellular inhibition.