Co-transmission of dopamine and glutamate

In the 1934 Dixon lectures, Sir Henry Dale articulated that the chemical nature of each neuron is fixed and unchangeable (Dale, 1935). John Eccles elevated these observations to a principle in 1954 when he and colleagues postulated that “the same chemical transmitting substance is used at all junctions operated by a particular cell” (Eccles et al., 1954). Dale’s Principle had thus been interpreted to mean that each neuron used a single neurotransmitter, although Eccles later suggested that multiple substances may be released (Eccles, 1976). The pioneering work of Dale’s gave way to current models of multi-neurotransmitter modulation and co-release of neurotransmitters. Specifically in the striatum, Kocsis and Kitai (1977) demonstrated that stimulation of midbrain neurons produce a dual excitatory EPSP comprised of a fast and slow component, suggesting the involvement of glutamate and dopamine in this system. A recent study provided evidence of cholinergic and glutamatergic co-transmission from medial habenula (Ren et al., 2011). The medial habenula projects to the interpeduncular nucleus and is involved in aversive states such as pain or nicotine withdrawal (Salas et al., 2009). Photostimulation of habenular neurons expressing channelrhodopsin under control of the ChAT promoter produced both slow nicotinic currents and rapid glutamatergic currents (Ren et al., 2011). Other recent studies demonstrated glutamatergic co-release from dopaminergic and serotonergic cells (Chuhma et al., 2004; Varga et al., 2009; Hnasko et al., 2010), suggesting that co-release may be a general mechanism used in modulatory neurons to increase their repertoire of neurotransmitter actions. The principal projection neuron in both the ventral and dorsal striatum is the GABAergic medium spiny neuron, the postsynaptic target of convergent input from distal glutamatergic and midbrain dopaminergic neurons. Midbrain dopamine neurons very densely innervate the striatum where the released dopamine, among other things, modulates excitatory glutamatergic transmission in this region. In this Journal Club article, I review the contribution of Stuber et al. (2010) to striatal circuitry. Here, they reported that midbrain dopaminergic neurons that project to the nucleus accumbens