Evidence for a glutamatergic projection from the zona incerta to the basal ganglia of rats

Abstract

This study explores the organisation and neurochemical nature of the projections from the zona incerta (ZI) to the basal ganglia. Sprague-Dawley rats were anaesthetised with ketamine (100 mg/kg) and Rompun (10 mg/kg), and injections of cholera toxin subunit B were made into each of the following nuclei: the ZI, the substantia nigra (SN), the pedunculopontine tegmental nucleus (PpT), and the entopeduncular nucleus (Ep). Brains were aldehyde fixed, sectioned, and processed using standard methods. Tracer-labelled sections were then doubly labelled with antibodies to glutamate (Glu), nitric oxide synthase (NOS), parvalbumin (Pv), or glutamic acid decarboxylase (GAD; the latter two are markers for GABAergic cells); these neurochemicals characterise most types of ZI cells. After ZI injections, labelling was nonuniform across the different basal ganglia nuclei. The bulk of labelling, both anterograde and retrograde, was seen in the SN and PpT and, to a lesser extent, within the other nuclei of the basal ganglia (e.g., caudate-putamen, globus pallidus, subthalamus, Ep). In the SN, labelling was found in both major parts of the nucleus, the pars compacta and pars reticulata. Within the PpT, however, the bulk of labelling was limited to only one of the two sectors of the nucleus, namely, the pars dissipata (PpTd). The pars compacta of the PpT (PpTc) remained largely free of labelled profiles. After CTb injections into three basal ganglia nuclei (SN, PpT, Ep), most labelled cells in the ZI were glutamate+ and very few were NOS+ or gamma-aminobutyric acidergic. Overall, the results indicate that the ZI is in a position to influence preferentially the activity of the SN and PpTd of the basal ganglia via an excitatory, glutamatergic input.

Subthalamic nucleus stimulation in Parkinson’s disease

“…Neurochemical studies have demonstrated that the zona incerta has preferential glutamatergic interconnections with both parts of substantia nigra (pars caudata and pars reticulata) and the pedunculopontine nucleus pars reticulata [26]. Glutamatergic projections from pedunculopontine nucleus pars reticulata onto the medulla and spinal cord are related in particular to the initiation of walking [53].…”

Bilateral caudal zona incerta nucleus stimulation for essential tremor: outcome and quality of life

“…Its rostral component extends over the dorsal and medial surface of the STN whereas its caudal or motor component lies posteromedial to the STN 29 30…”

Atlas-Independent, Electrophysiological Mapping of the Optimal Locus of Subthalamic Deep Brain Stimulation for the Motor Symptoms of Parkinson Disease

“…Hamel et al [19] describe rat studies showing that various functions of the ZI are affected in PD. Heise and Mitrofanis [14] provide evidence for glutamatergic projections from the ZI to the basal ganglia, which may be involved in PD. Plaha et al [20] describe studies suggesting that the ZI is the region by which tremor-related oscillations are transmitted to the ventral intermediate nucleus.…”

“…Some models of STN DBS propose that high-frequency stimulation directly inhibits an overactive STN in PD, releasing the basal-ganglia motor circuitry from inhibition [9, 10], suggesting an optimal locus of stimulation within the STN. By contrast, other models propose that high-frequency stimulation of fibers of passage in the STN region replaces pathologic signal information flow in the basal ganglia, without direct STN inhibition [11-14]. …”