Dopamine D1 or D2 receptor‐expressing neurons in the central nervous system

Abstract

Dopamine signals mainly through D1 receptors (D1Rs) and D2 receptors (D2Rs); D1R-expressing or D2R-expressing neurons contribute to distinct reward and addictive behaviors. Traditionally, transgenic mice expressing green fluorescent protein (GFP) under D1R or D2R promoters are used for fluorescent verification in electrophysiology studies, whereas Cre mice are employed for behavioral research. However, it is unknown whether the same neuronal populations are targeted in GFP and Cre mice. Additionally, while D1Rs and D2Rs are known to be expressed in different striatal neurons, their expression patterns outside the striatum remain unclear. The present study addressed these two questions by using several transgenic mouse lines expressing fluorescent proteins (GFP or tdTomato) or Cre under the control of D1R or D2R promoters. We found a high degree of overlap between GFP-positive and Cre-positive neurons in the striatum and hippocampus. Additionally, we discovered that D1Rs and D2Rs were highly segregated in the orbitofrontal cortex, prefrontal cortex, dorsal and ventral hippocampus, and amygdala: ~4-34 percent of neurons co-expressed these receptors. Importantly, slice electrophysiological studies demonstrated that D1R-positive and D1R-negative hippocampal neurons were functionally distinct in a mouse line generated by crossing Drd1a-Cre mice with a Cre reporter Ai14 line. Lastly, we discovered that chronic alcohol intake differentially altered D1R-positive and D2R-positive neuron excitability in the ventral CA1. These data suggest that GFP and Cre mice target the same populations of striatal neurons, D1R-expressing or D2R-expressing neurons are highly segregated outside the striatum, and these neurons in the ventral hippocampal may exert distinct roles in alcohol addiction.

Contrasting patterns of ERK activation in the tail of the striatum in response to aversive and rewarding signals

“…The direct visualization of D1R-and D2R-SPNs revealed that in the intermingled area, SPNs co-expressing both D1R and D2R were preferentially clustered adjacently to the corpus callosum. This contrasts with the homogenous distribution previously described in the anterior dorsal striatum (Gagnon et al 2017;Ren et al 2017;Wei et al 2018). The second territory, embedded between the striatum and the central amygdala is characterized by a high percentage of D1R/D2R-SPNs (~33%).…”

The role of fibroblast growth factor 2 in drug addiction

“…1). Striatal neurons mostly consist of GABAergic medium spiny neurons (MSN), which can be divided into two sub-populations as determined by the type of dopamine receptor they express: D1-or D2-expressing MSNs (Kreitzer & Malenka, 2008;Beaulieu & Gainetdinov, 2011;Gerfen & Surmeier, 2011;Calabresi et al, 2014;Wei et al, 2018). These neurons play opposite functional roles (Kreitzer & Malenka, 2008) in the socalled direct and indirect pathways, which were previously implicated in the action of drugs of abuse (Lobo & Nestler, 2011).…”

Effects of endogenous and exogenous D1/D5 dopamine receptor activation on LTP in ventral and dorsal CA1 hippocampal synapses

“…Although the dopaminergic innervation of the hippocampus appears to be relatively limited (Hortnagl, Berger, Sperk, & Pifl, ; Scatton et al, ; Swanson and Hartman, ; Swanson, Kohler, & Bjorklund, ), hippocampus is significantly populated by dopamine receptors (Hansen and Manahan‐Vaughan, ; Smith and Greene, ; Wei et al, ) and the functional impact of DA in the hippocampus neural circuitry is substantial (Frey et al, ; Hansen and Manahan‐Vaughan, ; Ito and Schuman, ; Kempadoo, Mosharov, Choi, Sulzer, & Kandel, ; Lisman and Otmakhova, ; Takeuchi et al ; Werlen and Jones, ). Importantly, the DAergic projections from the ventral tegmental area and the substantia nigra are disproportionately segregated along the hippocampal long axis.…”