The Role of Somatostatin in the Prefrontal Cortex
Restricted (Penn State Only)
- Author:
- Brockway, Dakota
- Graduate Program:
- Neuroscience
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- February 20, 2023
- Committee Members:
- Nikki Crowley, Chair & Dissertation Advisor
Janine Kwapis, Major Field Member
Sonia Cavigelli, Outside Unit Member
Yuval Silberman, Outside Field Member
Sonia Cavigelli, Professor in Charge/Director of Graduate Studies - Keywords:
- Prefrontal Cortex
Somatostatin
Neuropeptide
Pharmacology
Electrophysiology
Behavior - Abstract:
- Neurons communicate with rapid-acting neurotransmitters as well as through a variety of neuropeptides. Great strides have been made in elucidating synaptic neurotransmission, however there is a gap in our understanding of cellular and circuit level impacts of neuropeptides on brain function, cortical signaling, and behavior. Dysregulation of neuropeptide function and levels in the prefrontal cortex, a chief brain region regulating executive function, are observed following stress and substance use and accompanies almost every neuropsychiatric disease. Until recently, these neuropeptide signals were ‘invisible’ to neuroscientists, precluding a dissection of their function; however new technologies, and targeted experiments have enabled greater scientific efforts into the function of peptides throughout the brain - including in the prefrontal cortex (PFC). Somatostatin (SST) in the PFC is well positioned as a key modulator of executive function and an exemplar peptide for further targeting. SST neurons have been implicated in exploration, anxiety, fear, and substance use, suggesting SST may be an important regulatory molecule in these behaviors. SST is released from SST-expressing GABAergic neurons in the PFC and my work describes how it acts to modulate cortical signaling and alter behavior in a long-lasting fashion by acting on G protein-coupled receptors. In Chapter 1, I review the major findings concerning the action of neuropeptides in the PFC as well PFC-governed disease states, describing that neuropeptides including SST are implicated in the pathology of numerous neuropsychiatric disorders. In Chapter 2, I elucidate the neuromodulatory role of SST in the PFC to broadly dampen cortical signaling in a circuit and cell specific manner. Further, I reveal that SST acts to promote exploratory behaviors. In Chapter 3, I elucidate the impact of a mouse model of voluntary binge alcohol drinking on the SST peptide and its signaling. I found that binge drinking reduces SST release and causes deficits in SST signaling on pathway-agnostic pyramidal, neurons while preserving signaling onto pyramidal neurons specifically projecting to reward regions (nucleus accumbens). Overall interpretation, discussion, and future directions are presented in Chapter 4. This dissertation elucidates the role of the SST peptide on both signaling and behavior in the PFC, in both basal and disease states.