- • Pharmacological activation of nicotinic ACh receptors (nAChRs) excites striatal interneurones and induces a GABA-mediated current in medium spiny projecting neurones (MSNs) via feedforward inhibition.
- • Striatal interneurones identified as neuropeptide Y (NPY)+, parvalbumin (PV)+ and tyrosine hydroxylase (TH)+ have somatic expression of nAChRs.
- • The neurogliaform (NGF) subtype of NPY+ interneurones exhibits the most robust nicotinic response and has high synaptic connectivity with MSNs.
- • Antagonism of nAChR responses suggests the expression of distinct receptor subtypes between interneurone classes.
- • NPY+ NGF and TH+ interneurones mediate cholinergic control of MSNs and thus striatal output via GABAA receptors.
Abstract Choline acetyltransferase-expressing interneurones (ChAT)+ of the striatum influence the activity of medium spiny projecting neurones (MSNs) and striatal output via a disynaptic mechanism that involves GABAergic neurotransmission. Using transgenic mice that allow visual identification of MSNs and distinct populations of GABAergic interneurones expressing neuropeptide Y (NPY)+, parvalbumin (PV)+ and tyrosine hydroxylase (TH)+, we further elucidate this mechanism by studying nicotinic ACh receptor (nAChR)-mediated responses. First, we determined whether striatal neurones exhibit pharmacologically induced nicotinic responses by performing patch-clamp recordings. With high [Cl−]i, our results showed increased spontaneous IPSC frequency and amplitude in MSNs as well as in the majority of interneurones. However, direct nAChR-mediated activity was observed in interneurones but not MSNs. In recordings with physiological [Cl−]i, these responses manifested as inward currents in the presence of tetrodotoxin and bicuculline methobromide. Nicotinic responses in MSNs were primarily mediated through GABAA receptors in feedforward inhibition. To identify the GABAergic interneurones that mediate the response, we performed dual recordings from GABAergic interneurones and MSNs. Both TH+ and neurogliaform subtypes of NPY+ (NPY+ NGF) interneurones form synaptic connections with MSNs, although the strength of connectivity, response kinetics and pharmacology differ between and within the two populations. Importantly, both cell types appear to contribute to nAChR-mediated GABAergic responses in MSNs. Our data offer insight into the striatal network activity under cholinergic control, and suggest that subclasses of recently identified TH+ and NPY+ interneurones are key mediators of striatal nicotinic responses via GABAergic tonic and phasic currents.