The Effect of Estradiol on Striatal Synaptic Plasticity Underlying Goal-Directed Learning

Estradiol (E2), the predominant form of estrogen, has many neurological effects throughout the brain, including in synaptic processes thought to underlie various forms of learning and memory. One area of the brain in which estradiol exerts its effects is the dorsal striatum, a region of the basal ganglia associated with several functions including motor control and instrumental conditioning. Maladaptive changes in network function in the basal ganglia underlie substance use disorders, which involve changes in control over drug use between the two striatal subregions: from dorsomedial striatum (DMS)-based goal-directed learning to dorsomedial striatum (DLS)-based habitual learning. Males and females are found to exhibit differences in some striatal function, including dopamine activity, which may be related to known biological sex differences in substance use disorders. Furthermore, E2 has been found to impair several DMS- and DLS-based learning types in animals, which may underpin the sex difference in striatal function. However, estradiol mechanisms of action are unclear. Given that E2 is found to impair certain types of learning that involve the dorsal striatum, it is critical to understand the effect of E2 on striatal synaptic plasticity, a cellular process underlying learning. This dissertation uses ex vivo electrophysiology in male and female mouse brain slices to uncover the role of cycling female sex hormones and E2 receptors in particular in inhibiting synaptic plasticity in the DMS. This dissertation also explores DMS and DLS differences in the role of brain-derived neurotrophic factor (BDNF) on synaptic plasticity. The results from this dissertation uncover the identity of important modulators of the neurological substrates of learning that can have strong implications for substance use disorders.

Author

• Lewitus, Valerie Johanna

• BDNF
• dorsal striatum
• estradiol
• long-term potentiation
• substance use disorder
• synaptic plasticity

Identifier

hdl:1920/14474

OAI identifier oai:identifier

oai:MARS:1920/14474