GABAergic inputs from direct and indirect striatal projection neurons onto cholinergic interneurons in the primate putamen

Abstract

Striatal cholinergic interneurons (ChIs) are involved in reward-dependent learning and the regulation of attention. The activity of these neurons is modulated by intrinsic and extrinsic γ-aminobutyric acid (GABA)ergic and glutamatergic afferents, but the source and relative prevalence of these diverse regulatory inputs remain to be characterized. To address this issue, we performed a quantitative ultrastructural analysis of the GABAergic and glutamatergic innervation of ChIs in the postcommissural putamen of rhesus monkeys. Postembedding immunogold localization of GABA combined with peroxidase immunostaining for choline acetyltransferase showed that 60% of all synaptic inputs to ChIs originate from GABAergic terminals, whereas 21% are from putatively glutamatergic terminals that establish asymmetric synapses, and 19% from other (non-GABAergic) sources of symmetric synapses. Double pre-embedding immunoelectron microscopy using substance P and Met-/Leu-enkephalin antibodies to label GABAergic terminals from collaterals of “direct” and “indirect” striatal projection neurons, respectively, revealed that 47% of the indirect pathway terminals and 36% of the direct pathway terminals target ChIs. Together, substance P- and enkephalin-positive terminals represent 24% of all synapses onto ChIs in the monkey putamen. These findings show that ChIs receive prominent GABAergic inputs from multiple origins, including a significant contingent from axon collaterals of direct and indirect pathway projection neurons.

Learning-Related Translocation of δ-Opioid Receptors on Ventral Striatal Cholinergic Interneurons Mediates Choice between Goal-Directed Actions

“…Here we describe a new mechanism that, through predictive learning, allows CINs in the NAc-S to acquire the capacity of efficiently interrupting their activity through the accumulation of the DOR, an inhibitory G-protein-coupled receptor, in the membrane of these neurons. The endogenous ligand of DORs, enkephalin, is a good candidate for the source of this inhibition to CINs as it is produced by surrounding D 2 -containing MSNs, one of the two biggest populations of striatal projection neurons, with extensive inputs onto CINs (McGinty, 2007;Gonzales et al, 2013). It is noteworthy that DORs were found to be accumulating mainly in the somatic region of CINs, which is a hot spot of regulation for the efficient interruption of dendro-axonal communication (Freund and Katona, 2007).…”

Beclin-1- mediated autophagy may be involved in the elderly cognitive and affective disorders in streptozotocin-induced diabetic mice

“…Transmission electron microscopy (TEM, PHILIPS CM-120, Netherlands) Brain tissues were perfused with 2.5% glutaraldehyde perfusate (25% glutaraldehyde and 0.2 M phosphate buffer with 3mMMgCl2, pH 7.4), followed by fixation with 2.5% glutaraldehyde as previously described [28]. And then concentional of fixation solution, dehydrated, embedded in paraffin, sliced and 3% uranyl acetate and lead citrate double staining.…”

Anatomical localization of Cav3.1 calcium channels and electrophysiological effects of T-type calcium channel blockade in the motor thalamus of MPTP-treated monkeys

“…The tissue was prepared to localize Ca v 3.1 immunoreactivity using the pre-embedding immunogold method, according to a protocol used routinely in our laboratory (Gonzales et al 2013;Kuwajima et al 2007;Mitrano et al 2010). Sections were treated with sodium borohydride and processed with the cryoprotectant protocol described above.…”

“…The immunoreactive elements were classified based on ultrastructural features (Peters et al 1991), and the relative distribution of Ca v 3.1 immunoreactivity amongst neuronal elements was then statistically compared between normal and MPTP-treated animals using a Mann-Whitney test. Labeled dendrites were divided into small (Ͻ0.5 m), medium (0.5-1 m), or large (Ͼ1 m) profiles, based on their cross-sectional diameter (Galvan et al 2014;Gonzales et al 2013;Villalba et al 2006). The immunogold-stained sections were used to confirm expression of Ca v 3.1 labeling on the plasma membrane and at synaptic sites along immunoreactive dendrites.…”