Anxiety disorders, including post-traumatic stress disorder (PTSD), affect about 40 million American adults each year (18% of the population) and thus represent a major health problem. The main brain system involved in fear and anxiety is the amygdala, including its connections with discrete forebrain and brainstem regions. Studies of emotional learning in the amygdala have identified many of the neural circuits and mechanisms involved in normal fear and anxiety, and have suggested ways in which alterations in these mechanisms can provoke anxiety disorders. However, much more needs to be learned about these circuits before more effective treatments can be developed. The proposed study is the continuation of a long-term investigation of the synaptic organization of the basolateral nuclear complex of the rat amygdala (BLC) whose main goal is to elucidate the basic chemical neuroanatomy of amygdalar circuits involved in emotion, including emotional learning. In the present project we focus on the synaptic organization of inputs from three transmitter-specific neuromodulatory systems of the brainstem and basal forebrain. These include noradrenergic and dopaminergic systems of the brainstem, as well as the cholinergic/GABAergic inputs from the basal forebrain. Despite the importance of these systems for the physiology and pathophysiology of amygdalar emotional function, there have been few studies of these circuits using state-of-the-art multiple- labeling light and electron microscopic methods.
Specific Aim #1 will analyze the innervation of the BLC by cholinergic and GABAergic neurons of the basal forebrain.
Specific Aim #2 will study the Innervation of pyramidal cells and distinct interneuronal subpopulations by noradrenergic inputs to the BLC.
Specific Aim #3 will examine the dopaminergic innervation of the BLC, and its interactions with dopamine receptors and glutamatergic sensory inputs from the temporal cortex. The overarching hypothesis of this research is that there is a parcellation of emotional mnemonic subfunctions subserved by separate neuromodulatory systems projecting to the BLC, and that this will involve the differential targeting of discrete neuronal subpopulations and compartments by different neuromodulatory systems, and by the expression of different receptor subtypes in distinct neuronal subpopulations. Anxiety disorders, including post-traumatic stress disorder (PTSD), affect about 40 million American adults each year (18% of the population) and thus represent a major health problem. The main brain system involved in fear and anxiety is the amygdala, including its connections with discrete forebrain and brainstem regions. The proposed study is the continuation of a long-term investigation of the synaptic organization of the basolateral nuclear complex of the rat amygdala (BLC) whose main goal is to elucidate the basic chemical neuroanatomy of amygdalar systems involved in emotion.

Public Health Relevance

Anxiety disorders, including post-traumatic stress disorder (PTSD), affect about 40 million American adults each year (18% of the population) and thus represent a major health problem. The main brain system involved in fear and anxiety is the amygdala, including its connections with discrete forebrain and brainstem regions. The proposed study is the continuation of a long-term investigation of the synaptic organization of the basolateral nuclear complex of the rat amygdala (BLC) whose main goal is to elucidate the basic chemical neuroanatomy of amygdalar systems involved in emotion.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA027305-13
Application #
8267068
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Pilotte, Nancy S
Project Start
1999-07-01
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2014-05-31
Support Year
13
Fiscal Year
2012
Total Cost
$306,817
Indirect Cost
$90,749
Name
University of South Carolina at Columbia
Department
Pharmacology
Type
Schools of Medicine
DUNS #
041387846
City
Columbia
State
SC
Country
United States
Zip Code
29208
Zhang, J; Muller, J F; McDonald, A J (2013) Noradrenergic innervation of pyramidal cells in the rat basolateral amygdala. Neuroscience 228:395-408
Muller, Jay F; Mascagni, Franco; Zaric, Violeta et al. (2013) Muscarinic cholinergic receptor M1 in the rat basolateral amygdala: ultrastructural localization and synaptic relationships to cholinergic axons. J Comp Neurol 521:1743-59
Pinard, C R; Mascagni, F; McDonald, A J (2012) Medial prefrontal cortical innervation of the intercalated nuclear region of the amygdala. Neuroscience 205:112-24
McDonald, A J; Muller, J F; Mascagni, F (2011) Postsynaptic targets of GABAergic basal forebrain projections to the basolateral amygdala. Neuroscience 183:144-59
McDonald, A J; Mascagni, F (2011) Neuronal localization of M2 muscarinic receptor immunoreactivity in the rat amygdala. Neuroscience 196:49-65
Muller, Jay F; Mascagni, Franco; McDonald, Alexander J (2011) Cholinergic innervation of pyramidal cells and parvalbumin-immunoreactive interneurons in the rat basolateral amygdala. J Comp Neurol 519:790-805
McDonald, Alexander Joseph; Mascagni, Franco (2010) Neuronal localization of m1 muscarinic receptor immunoreactivity in the rat basolateral amygdala. Brain Struct Funct 215:37-48
Pinard, Courtney R; Mascagni, Franco; Muller, Jay F et al. (2010) Limited convergence of rhinal cortical and dopaminergic inputs in the rat basolateral amygdala: an ultrastructural analysis. Brain Res 1332:48-56