Reciprocal interaction between striatal cholinergic and low-threshold spiking interneurons - A computational study

The striatum is the main input stage of the basal ganglia receiving extrinsic input from cortex and thalamus. The striatal projection neurons (SPN) constitute 95% of the neurons in the striatum in mice while the remaining 5% are cholinergic and GABAergic interneurons. The cholinergic (ChIN) and low-threshold spiking interneurons (LTS) are spontaneously active and form a striatal subnetwork involved in salience detection and goal-directed learning. Activation of ChINs has been shown to inhibit LTS via muscarinic receptor type 4 (M4R) and LTS in turn can modulate ChINs via nitric oxide (NO) causing a prolonged depolarization. Thalamic input prefentially excites ChINs, whereas input from motor cortex favours LTS, but can also excite ChINs. This varying extrinsic input with intrinsic reciprocal, yet opposing, effects raises the possibility of a slow input-dependent modulatory subnetwork. Here, we simulate this subnetwork using multicompartmental neuron models that incorporate data regarding known ion channels and detailed morphological reconstructions. The modelled connections replicate the experimental data on muscarinic (M4R) and nitric oxide modulation onto LTS and ChIN, respectively, and capture their physiological interaction. Finally, we show that the cortical and thalamic inputs triggering the opposing modulation within the network induce periods of increased and decreased spiking activity in ChINs and LTS. This could provide different temporal windows for selective modulation by acetylcholine and nitric oxide, and the possibility of interaction with the wider striatal microcircuit.