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. 2024 May 22;81(9):870–881. doi: 10.1001/jamapsychiatry.2024.1112

Figure 5. Roles of β1-Adrenoceptor (β1-AR), L-Type Calcium Channel (LTCC), and SK Channels in Dorsolateral Prefrontal Cortex (dlPFC) Delay Cell Firing.

Figure 5.

The left subpanels show the mean (SEM) delay-related firing for all delay cells under control vs drug conditions; the right subpanels show the mean (SEM) d’ measure of spatial tuning for all delay cells under control vs drug conditions. A, The β1-AR agonist xamoterol (orange) was associated with reduced delay-related firing of dlPFC delay cells for the neurons’ preferred direction but not for nonpreferred directions (R 2-way analysis of variance, F1,19 = 12.99; P = .002), leading to a significant reduction in the d’ measure of spatial tuning (paired t test, t19 = 4.68; P < .001). B, Conversely, the β1-AR antagonist betaxolol (green) was associated with enhanced delay-related firing (R 2-way analysis of variance, F1,10 = 6.42; P = .03), and increased d’ measures of spatial tuning (paired t test, t10 = 3.36; P = .007). C, The reducing effects of the β1-AR agonist xamoterol were blocked by pretreatment with the LTCC antagonist, diltiazem (R 2-way analysis of variance, F2,24 = 5.90; P = .008; Tukey multiple comparisons: preferred direction, control vs diltiazem plus xamoterol; P = .16; control vs xamoterol, P < .001; diltiazem plus xamoterol vs xamoterol, P = .002). D, The SK channel blocker NS8593 was significantly associated with increased delay firing for the neurons’ preferred direction, as well as a smaller increase for nonpreferred directions (R 2-way analysis of variance, F1,17 = 12.13; P = .003), leading to a significant increase in d’ measure of spatial tuning (paired t test, t17 = 2.18; P = .04). E, The mean firing rate of 14 dlPFC delay cells, showing that the reducing effects of the LTCC agonist S-Bay were blocked by pretreatment with the SK channel antagonist NS8593 (R 2-way analysis of variance, F2,26 = 5.89; P = .008). F, The mean firing rate of 12 dlPFC delay cells, showing that the reducing effects of the LTCC agonist S-Bay were blocked by pretreatment with the hyperpolarization-activated and cyclic nucleotide–gated channel antagonist ZD7288 (R 2-way analysis of variance, F2,22 = 13.47; P < .001).

aP < .001.

bP < .005.

cP < .0001.

dP < .05.