|Department:||Pharmacology, Physiology, & Neuroscience|
B.S., Duke University (Magna Cum Laude)|
Ph.D., West Virginia University
Research in the McDonald lab focuses on a brain area known as the amygdala, which is one of the main brain regions regulating emotional learning and behavior. There is currently considerable interest in the amygdala because of its involvement in fear/anxiety, post-traumatic stress disorder (PTSD), and Alzheimer's disease. The current research in the lab focusses on the modulation of amygdalar neurons and their inputs by the neurotransmitter acetylcholine via muscarinic cholinergic receptors (mAChRs). The cholinergic innervation of the amygdala by the basal forebrain is much greater than that of any other brain area, and both the basal forebrain and amygdala exhibit severe degeneration in Alzheimer's disease (AD). There is evidence that this neuronal degeneration is critical for much of the memory loss in AD. In collaboration with the Mott lab in our department, we are systematically exploring the molecular, cellular, and network-level mechanisms by which activation of distinct mAChRs modulate amygdalar neurocircuitry. These comprehensive studies combine multiple-labeling confocal and electron microscopy with state-of-the-art electrophysiology and optogenetics. The objective of these studies is to determine how synaptically-released acetylcholine, acting on mAChRs, regulates neuronal oscillations, synaptic transmission and plasticity in the BL. This information is critical for the development of novel therapies to ameliorate neuropsychiatric such as anxiety disorders and the emotional and memory impairments seen in Alzheimer’s disease.
Fig. 1. (left) Electron micrograph of a spine of a pyramidal cell in the amygdala that expresses M1 muscarinic receptor immunoreactivity (M1sp; see particulate M1-ir). It receives a synapse from a cholinergic axon terminal (Vt; arrowhead) and an excitatory terminal that expresses M1-ir (M1t; asterisk)
Fig. 2. (right) Biocytin-filled interneuron in the amygdala recorded from a brain slice. Lower left insert: Post-hoc immunohistochemistry showed it to be a parvalbumin-ir interneuron (arrow). Upper right insert: Recording demonstrating a muscarinic current in this neuron.
- Fajardo-Serrano A, Liu L, Mott DD, McDonald AJ (2017) Evidence for M2 muscarinic receptor modulation of axon terminals and dendrites in the rodent basolateral amygdala: an ultrastructural and electrophysiological analysis. Neuroscience 357:349-362.
- Muller JF, Mascagni F, Zaric V, Mott, DD, McDonald AJ (2016) Localization of the m2 muscarinic cholinergic receptor in dendrites, cholinergic terminals and non-cholinergic terminals in the basolateral amygdala: An ultrastructural analysis. J Comp Neurol. 524:2400-2417.
- McDonald AJ, Mott DD (2016) Functional neuroanatomy of amygdalohippocampal interconnections and their role in learning and memory. Journal of Neuroscience Research 95:797-820. Invited Review.
- Zhang J, McDonald AJ (2016) Light and electron microscopic analysis of enkephalin-like immunoreactivity in the basolateral amygdala, including evidence for convergence of enkephalin and norepinephrine-containing axon terminals onto common targets. Brain Research 1636:62-73.
- McDonald AJ, Zaric V (2015) Extrinsic origins of the somatostatin and neuropeptide Y innervation of the rat basolateral amygdala. Neuroscience 294: 82-100.
- Zhang J, Muller JF, McDonald AJ (2015) Mu opioid receptor localization in the basolateral amygdala: an ultrastructural Analysis. Neuroscience. 303:352-363.
- Chakrabarti M, McDonald AJ, Reed JW, Moss MA, Das BC, Ray SK (2015) Molecular signaling mechanisms of natural and synthetic retinoids for inhibition of pathogenesis in Alzheimer's disease. Journal of Alzheimer's Disease 50:335-352.
- McDonald AJ, Zaric V (2015) GABAergic somatostatin-immunoreactive neurons in the amygdala project to the entorhinal cortex. Neuroscience 290:227-242.
- McDonald, A.J. (2014) Amygdala. In: Encyclopedia of the Neurological Sciences. Second Edition. M.J. Aminoff and R.B. Daroff (eds.), Vol. 1, pp.124-128. Elsevier.
PubMed Link: https://www.ncbi.nlm.nih.gov/pubmed?term=McDonald%20aj