Figure 2.

Cortical evoked EPSCs are negatively modulated by histamine acting at H₃ receptors. A, A Z-stack projection of an MSN labeled with biocytin in the dorsal striatum of a D2-GFP mouse. The labeled neuron shows the typical appearance of an MSN with densely spiny dendrites. B, Post hoc immunolabeling of biocytin-labeled neurons reveals GFP-positive (left) or GFP-negative MSNs (right) in a D2-GFP transgenic mouse. Insets show the labeled neurons through the red and green channels at higher magnification. Ci, Diagram of the stimulating and recording paradigm and example single-sweep traces of EPSCs recorded from MSNs while electrically stimulating the external capsule before, during and after application of histamine (10 μm). The first negative deflection is the stimulus artifact. Note the marked reduction in the amplitude of the EPSC in the presence of histamine. In this and subsequent figures the numbers on traces correspond to time points in the trace in Cii. Infrared differential interference contrast (IRDIC) image and fluorescence image of recording condition showing location of stimulating and recording electrodes. Cii, Plot of average, normalized EPSC amplitude (mean ± SEM) before, during and after application of histamine. A reduction in EPSC amplitude occurred in both D1 and D2 MSNs. Ciii, Bar plot of average, normalized EPSC amplitude in the presence of histamine, in conjunction with the H₃ receptor antagonist, thioperamide (10 μm) or thioperamide alone. The histamine-mediated reduction in EPSC amplitude (baseline vs histamine; p < 0.05) is blocked by coapplication of thioperamide (histamine vs histamine + thioperamide; p < 0.05 and p < 0.01), indicating that the effect is mediated through H₃ receptors.