Figure 3.

Thalamic evoked EPSCs are negatively modulated by histamine acting at H₃ receptors. A, Thalamic neurons in the intralaminar nuclei expressing both ChR2-YFP (green) following the injection of AAV (left). Section has been stained with Nissl-Cy5 to facilitate anatomical characterization (blue). Membrane expression of ChR2-YFP in both the soma and processes of infected thalamic neurons can be seen at higher magnification (right). fr, Fasciculus retroflexus, mt, mammillothalamic tract, DG, dentate gyrus, CA1 and CA3: cornu ammonis 1 and 3 of the hippocampus. B, The class of MSN was determined by immunolabeling the biocytin-labeled MSNs (red) for PPE (blue) defining the neuron as a PPE⁺, presumed indirect pathway MSN. Note also the YFP-expressing thalamic fibers labeled in green. Ci, Diagram of the stimulating and recording paradigm and example single-sweep traces of EPSCs recorded from MSNs while optically stimulating the thalamic afferents before, during and after application of histamine (10 μm). IRDIC and fluorescence image of recording condition showing location of recording electrode (left) and YFP-expressing thalamic fibers (right). Cii, Plot of average, normalized EPSC amplitude before, during and after application of histamine (10 μm). A reduction in EPSC amplitude was observed in both PPE⁻ and PPE⁺ MSNs i.e., presumed direct and indirect pathway 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 < 0.01) is blocked by coapplication of thioperamide (histamine vs histamine + thioperamide; p < 0.01) indicating that the effect is mediated through H₃ receptors.