Dopaminergic activation excites rat lateral habenular neurons in vivo

The lateral habenular complex (LHb) of the epithalamus is part of a dorsal diencephalic conduction system connecting basal forebrain with regulatory midbrain nuclei. The LHb has been implicated in the regulation of ascending monoaminergic transmission, particularly midbrain dopaminergic neuronal activity. Here, we have investigated whether the LHb in turn is subject to dopaminergic modulation. Alterations in spontaneous neuronal activity within the LHb following systemic application of dopaminergic drugs have been examined in anesthetized rats using extracellular single unit recordings. The administration of apomorphine (2 mg/kg) resulted in an excitation of individual LHb neurons. On average, the spontaneous action potential firing of the LHb neurons was increased by 39%. However, the apomorphine effect showed marked topographic differences within the LHb. Particularly, a small subset of neurons in the lateral division of the LHb, which was localized within the oval subnucleus, showed an apomorphine-mediated increase in discharge frequency by 96%. In contrast, spontaneous discharge of neurons within other areas of the lateral division was not modified. Likewise, within the medial division of the LHb, a region that preferentially receives projections from dopaminergic midbrain nuclei, the majority of neurons failed to show apomorphine-mediated alterations in action potential firing. However, within the superior subnucleus of this division, an area with yet unclear afferent supply, spontaneous neuronal firing was enhanced by 56%. The apomorphine-mediated excitation of LHb neurons was antagonized by coapplication of haloperidol (2 mg/kg), which alone did not alter spontaneous action potential firing of individual LHb neurons. The present study demonstrates that spontaneous activity of distinct subsets of neurons within the LHb is strongly enhanced by systemic activation of dopaminergic receptors. Despite the small sample size, the data suggest that this dopaminergic modulation shows a topographic specificity. Therefore, the results support the hypothesis of a functional subnuclear organization of the rat habenular complex.