An in vitro analysis of striatal microcircuitry

Low threshold spiking interneurons (LTSIs) and cholinergic interneurons are subtypes of striatal neurons that play an important role in modulation of final striatal output. This thesis describes an in vitro electrophysiological investigation of the mutual control of LTSIs and cholinergic interneurons. Moreover, this thesis describes the effects of three classes of opiate receptors agonists on LTSIs and cholinergic interneurons were investigated. Experiments were carried out using transgenic NPY-GFP mice or transgenic ChR2-EYFP-SOM-IRES-Cre mice. Whole-cell, perforated-whole cell and cell-attached recordings were obtained from mice brain slices maintained in vitro.

Our data report the presence of both GABAergic and cholinergic tones controlling LTSIs. Endogenous acetylcholine modulates LTSIs both directly and indirectly. The main direct effect of endogenous acetylcholine is inhibition of LTSIs through muscarinic cholinergic receptors. On the other hand, the main indirect effect of endogenous acetylcholine is activation of LTSIs. Moreover, endogenous acetylcholine inhibits the GABAergic transmission on LTSIs.
Furthermore, blue light- activation of LTSIs depolarized the cholinergic interneurons. This depolarization was only blocked by NO synthase inhibitor (L-NAME; 100 µM). These results indicate that the LTSIs exert a main stimulatory effect on the cholinergic interneurons mediated by nitric oxide through s-GMP independent mechanism.
Regarding the opioidergic control of LTSIs and cholinergic interneurons, our data report that δ receptor agonist (DPDPE; 1 µM) and κ receptor agonist (U-50488 hydrochloride; 10 µM) strongly inhibit LTSIs and cholinergic interneurons. Moreover, DPDPE inhibits GABAergic transmission on LTSIs but U-50488 does not affect the GABAergic transmission on LTSIs.

Furthermore, µ receptor agonist (DAMGO; 1 µM) has dual effect on LTSIs. The dual effect persisted in the presence of TTX. When GABAA, nicotinic and muscarinic receptors were blocked in presence of TTX, DAMGO always inhibited LTSIs. DAMGO also inhibited the GABAergic transmission on LTSIs.