Marked Differences in the Number and Type of Synapses Innervating the Somata and Primary Dendrites of Midbrain Dopaminergic Neurons, Striatal Cholinergic Interneurons, and Striatal Spiny Projection Neurons in the Rat Rachel J. Sizemore, Rong Zhang, Naili Lin, Liping Goddard, Timothy Wastney, Louise C. Parr-Brownlie, John N.J. Reynolds, and Dorothy E. Oorschot* Department of Anatomy, Otago School of Medical Sciences, and the Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand ABSTRACT Elucidating the link between cellular activity and goal- directed behavior requires a fuller understanding of the mechanisms underlying burst firing in midbrain dopami- nergic neurons and those that suppress activity during aversive or non-rewarding events. We have character- ized the afferent synaptic connections onto these neu- rons in the rat substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA), and compared these findings with cholinergic interneurons and spiny projec- tion neurons in the striatum. We found that the average absolute number of synapses was three to three and one-half times greater onto the somata of dorsal striatal spiny projection neurons than onto the somata of dopa- minergic neurons in the SNpc or dorsal striatal choliner- gic interneurons. A similar comparison between populations of dopamine neurons revealed a two times greater number of somatic synapses on VTA dopaminer- gic neurons than SNpc dopaminergic neurons. The per- centage of symmetrical, presumably inhibitory, synaptic inputs on somata was significantly higher on spiny pro- jection neurons and cholinergic interneurons compared with SNpc dopaminergic neurons. Synaptic data on the primary dendrites yielded similar significant differences for the percentage of symmetrical synapses for VTA dopaminergic vs. striatal neurons. No differences in the absolute number or type of somatic synapses were evi- dent for dopaminergic neurons in the SNpc of Wistar vs. Sprague-Dawley rat strains. These data from identi- fied neurons are pivotal for interpreting their electro- physiological responses to afferent activity and for generating realistic computer models of neuronal net- works of striatal and midbrain dopaminergic function. J. Comp. Neurol. 524:1062–1080, 2016. VC 2015 Wiley Periodicals, Inc. INDEXING TERMS: substantia nigra pars compacta; ventral tegmental area; dorsal striatum; synaptic innervation; transmission electron microscopy; RRID:AB_39024; RRID:AB_94647 The relationship between the anatomy of neural cir- cuits and their function is central to understanding information processing in the brain. Dopaminergic neu- rons in the ventral midbrain play key roles in reward processing, learning, memory, and movement (Omel- chenko et al., 2009). Their dysfunction is implicated in a number of disorders, including Parkinson’s disease, schizophrenia, and drug addiction (Wise, 2004). Under- standing the morphological bases of behavioral control requires characterization of the afferents that regulate firing patterns in midbrain dopaminergic neurons, Rong Zhang’s current address is The Liggins Institute, University of Auckland, Auckland 1142, New Zealand Grant sponsor: Health Research Council of New Zealand (to D.E.O); Grant sponsor: Neurological Foundation of New Zealand (to D.E.O., L.F.B., R.J.S); Grant sponsor: Lottery Grants Board of New Zealand (to D.E.O); Grant sponsor: Royal Society of New Zealand Marsden Fund (to J.N.J.R., D.E.O); Grant sponsor: Strategic Research Fund of the Department of Anatomy (to D.E.O); Grant sponsor: Nga Pae o te Maramatanga (to R.J.S); Grant sponsor: University of Otago (to R.Z). *CORRESPONDENCE TO: Associate Professor Dorothy E. Oorschot, PhD, Department of Anatomy, University of Otago, P.O. Box 913, Dunedin 9054, New Zealand. E-mail: dorothy.oorschot@anatomy.otago.ac.nz Received December 21, 2013; Revised August 17, 2015; Accepted September 2, 2015. DOI 10.1002/cne.23891 Published online October 7, 2015 in Wiley Online Library (wileyonlinelibrary.com) VC 2015 Wiley Periodicals, Inc. 1062 The Journal of Comparative Neurology | Research in Systems Neuroscience 524:1062–1080 (2016) RESEARCH ARTICLE