2023 Theses Doctoral

The Role of the Tail of the Striatum in Associative Learning

Stanley, Adrien Trejo

Associative learning is critical for survival. For example, learning to associate environmental cues with threat or safety is required to optimize avoidance and foraging behaviors. I focus here on how sounds may become associated with threat or safety in mice. Much is known about neural circuits mediating threat association learning, however, relatively little is known about those that mediate safety association learning. One brain area implicated in safety learning that is well positioned to integrate sensory cues and influence behavior is the tail of the striatum (TS). Local field potentials in the TS increase in response to safety-associated auditory cues. However, which TS cell type shows this increase and the causal relationship between this activity and learning is not known.

In Chapter 1, I review the currently literature on safety learning as well as functional implications of the TS which may relate to learned safety behavior.

In Chapter 2, I correlate learned safety behavior with TS activity selectively in D1 or D2 spiny projection neurons (SPNs) using fiber photometry. I find that TS SPNs of both populations showed increased calcium responses to learned safety cues that differed from learned threat cues. I also show that sound-safety associations induce a postsynaptic long-term potentiation at auditory thalamus to TS D1 SPN synapses.

In Chapter 3, I explore how TS SPN activity may relate to locomotion in neutral and threatening contexts. In Chapter 4, I explore how TS activity may relate to pain modulation. I find that TS activity is not modulated by pain intensity but is modulated by aversive stimulus duration. In Chapter 5, I explore how sound-safety learning alters serotonin release in the TS. I find that auditory cues and foot shocks produced transient decreases in serotonin release that is not modulated by sound-safety learning.

Finally, in Chapter 6, I depart from exploration of TS function and explore the role of norepinephrine in the cerebellum in sound-threat association learning. I find that sound-threat associated cues induce norepinephrine release in the cerebellum and norepinephrine signaling required for cued threat association.