Physiological Effects of Alcohol on Crayfish Escape Circuitry

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.

The Impact of Prenatal Nicotine Exposure on Impulsivity and Neural Firing in the Medial Prefrontal Cortex

Prenatal nicotine exposure (PNE) is linked to a large number of psychiatric disorders, including attention deficit hyperactivity disorder (ADHD). Current literature suggests that core deficits observed in ADHD reflect abnormal inhibitory control governed by the prefrontal cortex (PFC) of the brain. The PFC is structurally altered by PNE, but it is still unclear how neural firing is affected during tasks that test behavioral inhibition, such as the stop-signal task, or if neural correlates related to inhibitory control are affected after PNE in awake behaving animals. To address these questions, we recorded from single medial PFC (mPFC) neurons in control rats and PNE rats as they performed our stopsignal task. We found that PNE rats were faster for all trial types and were less likely to inhibit the behavioral response on STOP trials. Neurons in mPFC fired more strongly on STOP trials and were correlated with accuracy and reaction time. Although the number of neurons exhibiting significant modulation during task performance did not differ between groups, overall activity in PNE was reduced. We conclude that PNE makes rats impulsive and reduces firing in mPFC neurons that carry signals related to response inhibition.