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. Upper right insert: Recording demonstrating a muscarinic current in this neuron.
Research of 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 severe neuropsychiatric disorders, including the emotional and memory impairments seen in Alzheimer’s disease.
- Muller JF, Mascagni F, McDonald AJ (2013) Muscarinic cholinergic receptor M1 in the rat basolateral qmygdala: ultrastructural localization and synaptic relationships to cholinergic axons. J Comp Neurol. 521:1743-59
- Zhang J, Muller JF, McDonald AJ (2013) Noradrenergic innervation of pyramidal cells in the rat basolateral amygdala. Neuroscience 228:395-408.
- Pinard CR, Mascagni F, Muller JF, McDonald AJ (2012) Medial prefrontal cortical innervation of the intercalated nuclear region of the amygdala. Neuroscience 205:112-124.
- McDonald AJ, Mascagni F, Zaric V (2012) Subpopulations of somatostatin-immunoreactive nonpyramidal neurons in the amygdala and adjacent external capsule project to the basal forebrain: evidence for the existence of GABAergic projection neurons in the cortical nuclei and basolateral nuclear complex. Front Neural Circuits 6:46.
- Muller JF, Mascagni F, McDonald AJ (2011) Cholinergic innervation of pyramidal cells and parvalbumin-immunoreactive interneurons in the rat basolateral amygdala. J. Comp. Neurol. 519:790-805.
- McDonald AJ, Muller JF, Mascagni F (2011) Postsynaptic targets of GABAergic basal forebrain projections to the basolateral amygdala. Neuroscience 183:144-159.
- Dabrowska J, Ahern TH, Hazra R, McDonald AJ, Mascagni F, Muller JF, Young LJ, Rainnie DG (2011) Type 2 corticotrophin-releasing factor receptor-like (CRFR2) and oxytocin immunoreactive patterns overlap in the hypothalamus and bed nucleus of the stria terminalis (BNST). PsychoNeuroEndocrinology 36:1312-1326.
- McDonald AJ, Mascagni F (2011) Neuronal localization of m2 muscarinic receptor immunoreactivity in the rat amygdala. Neuroscience 196:49-65.