Date of Award

January 2023

Document Type


Degree Name

Doctor of Philosophy (PhD)


Biomedical Sciences

First Advisor

Saobo Lei


The amygdala is a limbic structure critical for emotional processing as well as roles in learning and memory. Disruption of the normal activity of the amygdala has been implicated in several disorders including phobia disorders, anxiety-like disorders, and substance abuse. The function of the amygdala and its role in various disorders is directly related to its underlying cellular activity. The amygdala is both a cortical- and striatal-like structure containing mainly glutamatergic and GABAergic neurons, respectively. This dissertation has three aims related to the neuropeptide modulation of these cell types in the basolateral (BLA) and central amygdala (CeA). The first aim addresses how the neuropeptide, neuromedin B (NMB), alters excitability within the CeA and contributes to cardiac output and fear responses. The second aim addresses how NMB modulates neuronal activity in the BLA and anxiety-like behaviors. Finally, the third aim studies the roles and mechanisms of neurokinin B-mediated modulation of neuronal excitability and fear responses.

For Study 1, bath application of NMB excited CeL neurons in vitro. NMB selectively activated bombesin 1 receptors (BB1Rs) increasing action potential firing that was dependent on the activity of PLC and PKC, but excitation was independent of Ca2+ flux. NMB enhanced CeL neuronal excitation by inhibiting inwardly rectifying K+ channels. Direct application of NMB into the CeA reduced mean arterial pressure and heart rate and reduced fear potentiated startle responses.

For Study 2, activation of BB1Rs excited BLA neurons and enhanced glutamatergic transmission. NMB-mediated excitation of BLA neurons was mediated through the activation of non-selective cation channels and depression of inwardly rectifying K+ channels. NMB enhanced spontaneous glutamatergic transmission but inhibited evoked glutamate responses through TRPV1 channels. Direct application of NMB into the BLA produced anxiogenic phenotypes in the Vogel Conflict Test.

For Study 3, selective activation of neurokinin 3 receptors (NK3Rs) with senktide or the endogenous ligand neurokinin B enhanced neuronal excitability of BLA neurons. NK3R-elicited excitation of BLA neurons is mediated by the activation of non-selective cation channels and depression of inwardly rectifying K+ channels. The NK3R-mediated excitation of BLA neurons required the function of PLC and cleavage of membrane phosphatidylinositol 4,5-bisphosphate. Direct application of senktide into the BLA augmented fear potentiated startle responses. TRPC4/5 and GIRK channels are involved in senktide-induced augmentation of fear potentiated startle responses.