Computational modeling of dSPN dendritic activity.

(A) Morphology of reconstructed dSPN with cartoon to illustrate the direction of stimulation along a dendrite. (B) Synaptic potentials recorded at the soma in response to clustered spine activation (18 neighboring glutamatergic synapses stimulated sequentially at 1 ms intervals) in 2 separate dendrites. A dendritic spike is generated to the distal (orange trace) but not proximal dendritic input (blue trace). The quarterdrop duration is defined as the time interval between the last stimulation and the time for the membrane voltage to drop by one quarter of its peak value. (C) Quarterdrop interval (ms) plotted as a function of path distance from the center of that dendrite to the soma (μm) for every dendrite with spines (50) of the reconstructed dSPN. Dendritic spikes were only reliably observed in distal dendrites (>100 μm from cell soma). (D) Onsite phasic GABAergic activation and glutamatergic activation delivered to the same distal dendrite. Synaptic potentials recorded at the dendrite (E) and soma (F). GABA synaptic activation comprised 3 simultaneous stimulations delivered 5 times at an interval of 1 ms to the midpoint of the dendrite. The timing of this phasic input was varied relative to a fixed clustered supra-threshold glutamatergic input (delivered to 18 spines; 1 ms interval as before) in intervals of 10 ms from −10 (blue) to 80 ms (orange). For comparison, the effect of glutamatergic activation alone is illustrated by a thick gray line. Onsite GABAergic activation causes a dramatic cessation of dendritic and somatic potentials in a manner consistent with the relative timing of the 2 inputs. (G) Offsite phasic GABAergic activation delivered to 4 distal dendritic locations. A clustered glutamatergic input (15 spines; 1 ms interval) delivered to the same dendrite as before resulted in a subthreshold synaptic potential (red) at the dendritic site of delivery (H) and soma (I). Similarly, the effect of only activating GABAergic synapses at 1 ms intervals at each of the 4 offsite dendritic locations simultaneously (3 per dendrite; 12 in total) resulted in a moderate postsynaptic potential (blue trace). When delivered sequentially, with GABAergic activation preceding glutamatergic by 10 ms, the previously subthreshold glutamatergic input (red traces) resulted in the generation of a spike (black trace; H and I). The data underlying the graphs shown in the figure can be found in dx.doi.org/10.5281/zenodo.10386854. SPN, spiny projection neuron.