Type
Text
Type
Dissertation
Advisor
Role, Lorna W | Kritzer, Mary | Talmage, David | Fontanini, Alfredo | Moore, Holly.
Date
2014-12-01
Keywords
acetylcholine, amygdala, fear, learning, optogenetic, synaptic transmission | Neurosciences
Department
Department of Neuroscience.
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/76584
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
The amygdala, a subcortical structure in the anterior temporal lobe, plays important roles in integrating sensory information from different brain areas, assigning emotional valence and effecting adaptive behavioral, physiological, and cognitive responses. Sensory inputs from cortical and thalamic sources, carrying highly processed sensory information and low level, more direct sensory information, respectively, converge in the basolateral nucleus of the amygdala (BLA). Here, neuromodulation by acetylcholine (ACh), released from inputs arising from the nucleus basalis of Meynert (NBM) in the basal forebrain, plays a major role in synaptic integration during different emotional arousal states. Using patch-clamp electrophysiology in acute brain slices from adult mice, I took advantage of the fact that these inputs project through spatially distinct fiber tracts, and stimulated either or both of these pathways while recording excitatory post-synaptic currents (EPSCs) in BLA pyramidal neurons. I found that while both the cortical and thalamic inputs have a similar baseline synaptic strength, they differ in their plasticity to patterned stimulation. Whereas cortical inputs readily potentiate, thalamic inputs are much more variable, showing either potentiation, depression, or no response at all. I subsequently used ChAT-Cre mice transfected with a floxed channelrhodopsin construct targeted to the NBM to compare the response of these inputs to optogenetic stimulation of endogenous cholinergic inputs to the BLA. I found that these inputs are oppositely modulated by endogenous ACh; while cortical inputs show synaptic potentiation, thalamic inputs show synaptic depression. Finally, optogenetic stimulation or inhibition of cholinergic inputs to BLA bidirectionally altered learning and memory in a cued fear conditioning paradigm. In sum, my work suggests that the influence of ACh on integration of inputs in the BLA is potent, input specific, and a key component of behavioral adaptation to fearful stimuli. With disorders such as PTSD an ever increasing problem, the amygdaloid circuitry underlying sensory integration and behavioral adaption represents an especially promising target for clinical intervention. | 155 pages
Recommended Citation
Lederman, James David, "Cholinergic modulation and integration of excitatory inputs to basolateral amygdala" (2014). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 2478.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/2478