Somatodendritic dopamine release: recent mechanistic insights

Abstract

One contribution of 16 to a discussion meeting issue 'Release of chemical transmitters from cell bodies and dendrites of nerve cells'. Dopamine (DA) is a key transmitter in motor, reward and cogitative pathways, with DA dysfunction implicated in disorders including Parkinson's disease and addiction. Located in midbrain, DA neurons of the substantia nigra pars compacta project via the medial forebrain bundle to the dorsal striatum (caudate putamen), and DA neurons in the adjacent ventral tegmental area project to the ventral striatum (nucleus accumbens) and prefrontal cortex. In addition to classical vesicular release from axons, midbrain DA neurons exhibit DA release from their cell bodies and dendrites. Somatodendritic DA release leads to activation of D2 DA autoreceptors on DA neurons that inhibit their firing via G-protein-coupled inwardly rectifying K þ channels. This helps determine patterns of DA signalling at distant axonal release sites. Somatodendritically released DA also acts via volume transmission to extrasynaptic receptors that modulate local transmitter release and neuronal activity in the midbrain. Thus, somatodendritic release is a pivotal intrinsic feature of DA neurons that must be well defined in order to fully understand the physiology and pathophysiology of DA pathways. Here, we review recent mechanistic aspects of somatodendritic DA release, with particular emphasis on the Ca 2þ dependence of release and the potential role of exocytotic proteins.

Striosome–dendron bouquets highlight a unique striatonigral circuit targeting dopamine-containing neurons

“…A reciprocal striatonigral pathway, returning to the dopamine-containing neurons of the substantia nigra pars compacta (SNc), is thought to regulate the activity of the dopamine-containing SNc neurons, potentially affecting nigrostriatal tract function as well as local dopamine release from ventrally extending dendrites of SNc neurons (1). Strikingly, this striatonigral pathway has been shown to originate mainly from the striosomal compartment (also known as "patches") of the striatum (2-4).…”

Cannabis use by women during pregnancy does not influence infant DNA methylation of the dopamine receptor DRD4

“…Dopamine signaling is involved in many cognitive processes, including memory and reward (15). Cannabis dependence is linked to a reduction in striatal dopamine release which is also correlated with poor working memory and learning performance (29).…”

“…CB 1 R is known to be co-expressed with dopamine receptors (14) and cannabis, like all recreational drugs, causes an increase in dopamine levels in the terminal regions of the mesolimbic dopamine system. Dopamine signaling is linked to memory, cognition, and is one of the major reward pathways in the brain implicated in drug addiction (15). Little is known about the effects of maternal cannabis use on methylation of genes involved in dopamine signaling in offspring.…”

Release of chemical transmitters from cell bodies and dendrites of nerve cells

“…Dysfunction of dopaminergic systems has been implicated in disorders that include Parkinson's disease, addiction and schizophrenia. In addition to exhibiting classical vesicular release of dopamine from their axon terminals, dopamine-containing midbrain neurons release the transmitter from their cell bodies and dendrites [30]. Axons of dopaminergic neurons in the brainstem project to the dorsal and ventral striatum and to the forebrain.…”