Biology Theses and Dissertations

Permanent URI for this collectionhttp://hdl.handle.net/1903/2749

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    INHIBITION IN THE CRAYFISH LATERAL GIANT CIRCUIT
    (2020) Winter, Lucy Soda Venuti; Herberholz, Jens; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    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.
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    Physiological Effects of Alcohol on Crayfish Escape Circuitry
    (2016) Swierzbinski, Matthew Edward; Herberholz, Jens; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Alcohol is one of the oldest and most widely used drugs on the planet, but the cellular mechanisms by which it affects neural function are still poorly understood. Unlike other drugs of abuse, alcohol has no specific receptor in the nervous system, but is believed to operate through GABAergic and serotonergic neurotransmitter systems. Invertebrate models offer circuits of reduced numerical complexity and involve the same cell types and neurotransmitter systems as vertebrate circuits. The well-understood neural circuits controlling crayfish escape behavior offer neurons that are modulated by GABAergic inhibition, thus making tail-flip circuitry an effective circuit model to study the cellular mechanisms of acute alcohol exposure. Crayfish are capable of two stereotyped, reflexive escape behaviors known as tail-flips that are controlled by two different pairs of giant interneurons, the lateral giants (LG) and the medial giants (MG). The LG circuit has been an established model in the neuroscience field for more than 60 years and is almost completely mapped out. In contrast, the MG is still poorly understood, but has important behavioral implications in social behavior and value-based decision making. In this dissertation, I show that both crayfish tail-flip circuitry are physiologically sensitive to relevant alcohol concentrations and that this sensitivity is observable on the single cell level. I also show that this ethyl alcohol (EtOH) sensitivity in the LG can be changed by altering the crayfish’s recent social experience and by removing descending inputs to the LG. While the MG exhibits similar physiological sensitivity, its inhibitory properties have never been studied before this research. Through the use of electrophysiological and pharmacological techniques, I show that the MG exhibits many similar inhibitory properties as the LG that appear to be the result of GABA-mediated chloride currents. Finally, I present evidence that the EtOH-induced changes in the MG are blocked through pre-treatment of the potent GABAA receptor agonist, muscimol, which underlines the role of GABA in EtOH’s effects on crayfish tail-flip circuitry. The work presented here opens the way for crayfish tail-flip circuitry to be used as an effective model for EtOH’s acute effects on aggression and value-based decision making.