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

Abstract

Elucidating the link between cellular activity and goal-directed behavior requires a fuller understanding of the mechanisms underlying burst firing in midbrain dopaminergic neurons and those that suppress activity during aversive or non-rewarding events. We have characterized the afferent synaptic connections onto these neurons in the rat substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA), and compared these findings with cholinergic interneurons and spiny projection 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 dopaminergic neurons in the SNpc or dorsal striatal cholinergic interneurons. A similar comparison between populations of dopamine neurons revealed a two times greater number of somatic synapses on VTA dopaminergic neurons than SNpc dopaminergic neurons. The percentage of symmetrical, presumably inhibitory, synaptic inputs on somata was significantly higher on spiny projection 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 evident for dopaminergic neurons in the SNpc of Wistar vs. Sprague-Dawley rat strains. These data from identified neurons are pivotal for interpreting their electrophysiological responses to afferent activity and for generating realistic computer models of neuronal networks of striatal and midbrain dopaminergic function.

A Viral Toolbox of Genetically Encoded Fluorescent Synaptic Tags

“…However, the punctate expression patterns and higher density of PSD95.FingR-labeled synapses than Gephyrin.FingR-labeled synapse suggest that the FingR vectors correctly identify excitatory and inhibitory synapses. Furthermore, the synaptic densities we report for excitatory synapses in adult-born granule cells and for inhibitory synapses in striatal cholinergic interneurons are in line with previous studies ( Sizemore et al., 2016 , 2010 ; Sultan et al., 2015 ; Toni et al., 2007 ; van Praag et al., 2002 ).…”

Neurobiological mechanisms associated with antipsychotic drug-induced dystonia

“…Striatal cholinergic interneurons receive afferent input with a wide variety of neurotransmitters (Lim et al, 2014), including glutamatergic input from especially the intralaminar thalamic nuclei (Assous and Tepper, 2019), nigrostriatal dopaminergic input (Lim et al, 2014) and cholinergic input from other cholinergic interneurons. Although dopaminergic projections to MSNs are by far more abundant than those on cholinergic interneurons (Sizemore et al, 2016), the majority of these interneurons express inhibitory dopamine D2 receptors next to excitatory D5 receptors, and about 20% contain low levels of excitatory D1 receptors (Lim et al, 2014). Nigrostriatal projections largely enhance the activity of certain CSTC circuits by affecting specific MSNs and modify the activity of a group of MSNs by inhibiting the more widespread activity of cholinergic interneurons.…”

Noncanonical Roles of hα-syn (A53T) in the Pathogenesis of Parkinson’s Disease: Synaptic Pathology and Neuronal Aging

“…Studies in different animal models have shown that the damage of dopaminergic neurons in the SNc is clear. This condition may be due to the following reasons: First, many synaptic connections exist in dopaminergic neurons in the SNc [45]. Thus, the frequency of neuron activity is high and accompanied by high metabolism.…”