Dual character, asynaptic and synaptic, of the dopamine innervation in adult rat neostriatum: A quantitative autoradiographic and immunocytochemical analysis

Abstract

Dopamine (DA) axon terminals (varicosities) in the neostriatum of adult rats were examined for shape, size, content, synaptic incidence, type of junction, synaptic targets, and microenvironment after electron microscopic identification either by [3H]DA uptake autoradiography or by immunocytochemistry with monoclonal antibodies against DA-glutaraldehyde-protein conjugate. Both approaches yielded comparable results. Whether they were from the paraventricular or the mediodorsal neostriatum, respectively, the [3H]DA-labeled and DA-immunostained varicosities were generally oblong and relatively small; more than 60% contained one or more mitochondria. Sixty to seventy percent were asynaptic, and 30-40% were endowed with a synaptic membrane differentiation (junctional complex), as inferred by stereological extrapolation from single thin sections (both approaches) or observed directly in long, uninterrupted series of thin sections (immunocytochemistry). The synaptic DA varicosities always displayed symmetrical junctions: 67% with dendritic branches, 30% with dendritic spines, and 2-3% with neuronal cell bodies. DA varicosities juxtaposed to one another were frequent. Other axonal varicosities were more numerous in the immediate vicinity of DA varicosities than around randomly selected, unlabeled terminals. The respective microenvironments of DA and unlabeled varicosities also showed enrichment in the preferred synaptic targets of both groups of varicosities, with dendritic branches for DA and dendritic spines for the unlabeled ones. These data suggest a dual mode of operation that is diffuse as well as synaptic for the nigrostriatal DA system. In such a densely DA-innervated brain region, they also lead to the hypothesis that a basal level of extracellular DA might be maintained permanently around every tissue constituent and, thus, contribute to the mechanisms of action, properties, and functions (or dysfunctions) of DA within the neostriatum itself and as part of the basal ganglia circuitry.

Occupancy of Striatal and Extrastriatal Dopamine D2 Receptors by Clozapine and Quetiapine

“…Both of these atypical APDs have a low affinity for the DA D 2 r (Schotte et al, 1996). Studies of striatal DA D 2 r indicate that, although a significant fraction are extrasynaptic, the majority of striatal DA D 2 r are located at synapses (Levey et al, 1993;Descarries et al, 1996). In the cortex, dopaminergic neurotransmission appears to be largely extrasynaptic or a volume mode Smiley et al, 1994;Sesack et al, 1998).…”

The role of transmitter diffusion and flow versus extracellular vesicles in volume transmission in the brain neural–glial networks

“…Recently, surface diffusion of astrocytic glutamate transporters were found to shape the kinetics of excitatory postsynaptic currents and thus synaptic transmission [32]. VT mediated by monoamines seems to depend on extrasynaptic release and transmitter spread to extrasynaptic receptors [11,14,15,18,33] since inter alia a large proportion of monoamine terminals lack postjunctional complexes [34,35]. Rice & Cragg [36] have modelled DA extrasynaptic transmission from terminals based on DA spillover after quantal release, considering a large number of experimental data from their own and other groups.…”

Cholinergic interneuron characteristics and nicotinic properties in the striatum

“…Rather, thinner parts of the axons contain vesicles and have specializations indicative of en passant type synapses. Evidence indicates that DA fibers do make synaptic connections (Pickel et al, 1981;Freund et al, 1984; but see Descarries et al, 1996), but "spillover" of DA from the synapse into the extracellular space may be common. Spillover, which has been recognized at other neurotransmitter synapses (Barbour and Hausser, 1997), is likely to be an important contributor to dopaminergic volume transmission in the striatum.…”