Synaptic relationships between dopaminergic afferents and cortical or thalamic input in the sensorimotor territory of the striatum in monkey

Abstract

The cerebral cortex and the intralaminar thalamic nuclei are the major sources of excitatory glutamatergic afferents to the striatum, whereas the midbrain catecholaminergic neurones provide a dense intrastriatal plexus of dopamine-containing terminals. Evidence from various sources suggests that there is a functional interaction between the glutamate- and dopamine-containing terminals in the striatum. The aim of the present study was to determine the synaptic relationships between cortical or thalamic inputs and the dopaminergic afferents in the sensorimotor territory of the monkey striatum. To address this issue, anterograde tracing in combination with immunocytochemistry for tyrosine hydroxylase (TH) was carried out by light and electron microscopy. Squirrel monkeys received injections of biocytin in the primary motor and somatosensory cortical areas or injections of either Phaseolus vulgaris-leucoagglutinin (PHA-L) or biocytin in the centromedian nucleus (CM) of the thalamus. Sections that included the striatum were processed to visualize the anterograde tracers alone or in combination with TH immunoreactivity. The anterogradely labelled fibres from the cerebral cortex and CM display a band-like pattern and are exclusively confined to the postcommissural region of the putamen, whereas TH-immunoreactive axon terminals are homogeneously distributed throughout the entire extent of the striatum. Electron microscopic analysis revealed that the anterogradely labelled terminals from the cerebral cortex form asymmetric synapses almost exclusively with the heads of dendritic spines. The thalamic terminals also form asymmetric synapses, but in contrast to cortical fibres, predominantly with dendrites (67.4%) and less frequently with spines (32.6%). The TH-immunoreactive boutons are heterogeneous in morphology. The most common type (84% of the total population) forms symmetric synapses; of these the majority is in contact with dendritic shafts (72.1%), less with spines (22.5%) and few with perikarya (5.4%). In sections processed to reveal anterogradely labelled cortical fibres and TH-immunoreactive structures, individual spines of striatal neurones were found to receive convergent synaptic inputs from both cortical and TH-immunoreactive boutons. In contrast, anterogradely labelled thalamic terminals and TH-immunoreactive boutons were never seen to form convergent synaptic contacts on the same postsynaptic structure. These findings suggest that the dopaminergic afferents are located to subserve a more specific modulation of afferent cortical input than afferent thalamic input in the sensorimotor territory of the striatum in primates.

Dopaminergic signaling in dendritic spines

“…A significant subpopulation of spines [15] is simultaneously contacted by both dopaminergic and glutamatergic varicosities [15][16], forming the "striatal microcircuit" or "synaptic triad" [17]. Similar DA innervation architecture is also observed in pyramidal neurons in the cortex and hippocampus, and magnocellualar neurons of basolateral amygdale [17,32].…”

“…However, a unique, disproportionately large population of DA receptors is localized in dendritic spines [11][12][13][14], where most of the excitatory glutamatergic synapses are formed. Moreover, a subset of DA receptor-containing spines is innervated simultaneously by both glutamatergic terminals and dopaminergic terminals [15][16][17]. DA receptors within dendritic spines differ from extraspinous receptors in that they are physically, and perhaps functionally, confined in the small compartment of spines.…”

“…The glutamatergic inputs from these regions are mediated by the densely populated spines on the dendrites of MSNs. Most DA varicosities are in contact with spines, and to a lesser extent with dendritic shafts and cell bodies of MSNs, forming axosomatic, axodendritic, and axospinous synapses [15][16] (Figure 2A). …”

“Early” and “Late” Effects of Sustained Haloperidol on Apomorphine- and Phencyclidine-induced Sensorimotor Gating Deficits

“…A second possible explanation for the delayed emergence of anti-PCP effects of haloperidol in this paradigm is that these effects may result from a direct augmentation of NMDA receptor processes (Banerjee et al 1995), or via changes in specific interactions between glutamate and DA receptors in frontal cortex (Cepeda et al 1992), striatum (Amalric et al 1994;Smith et al 1994) or nucleus accumbens (Svensson et al 1994) -all regions implicated in the regulation of PPI (Swerdlow et al 1992). Other reports suggest that subchronic perturbations of glutamatergic substrates via repeated injections of PCP are capable of modifying behavioral and neurochemical properties of brain DA systems (Jentsch et al 1997(Jentsch et al , 1998.…”

Subcellular and Subsynaptic Localization of Presynaptic and Postsynaptic Kainate Receptor Subunits in the Monkey Striatum

“…Because both cortical and thalamic afferents provide glutamatergic terminals forming asymmetric synapses in the monkey striatum (Sadikot et al, 1992;Smith et al, 1994), we tested whether KAR subunits were associated with both glutamatergic inputs. Injections of BDA were made in the centromedian nucleus of the thalamus or the primary motor cortex in two squirrel monkeys.…”