Dysfunction Of The Lateral Habenular D1 Receptor Effect On Emotions And Memory

Hb(Habenula nucleus,Hb) is an important hub that links the limbic forebrain and the dorsal brainstem. It mainly consists of the medial habenular nucleus(MHb) and lateral hanbenular nucleus(LHb), which participates in the regulation of many physiological activities through a variety of neurotransmitters. Recently, accumulating evidence suggest that Hb has an important role in cognition and emotion.The LHb is riciprically connected with midbrain dopamine system expecially the Ventral Tegmental Area (VTA). Hb contains dopamine type 1 and type 2 receptor (D1R,D2R). Previous researches mainly focus on the effects of LHb on dopamine system. Substatial evidences suggested abnormal activities of LHb neurons involved in depressive like behavior. But the role of DIR in the LHb in emotion is not clear. Futhemore, Some studies have showed that DIR in the LHb involves the cognitive progress especially with the spatial learning and attention. Hippocampus is a key brain area involved memory and emotion. The long-term potentiation(LTP) and long-term depression(LTD) are considered to be the molecular mechanism of learning and memory. Phosphorylation of GluRl subunit in the hippocampus is required for learning and memory and LTP. Accumulating evidence indicate that there is a functional link between LHb and hippocampus. LHb might be implicated in spatial memory processing through functional interaction with hippocampus. It is still not clear whether DIR in the LHb modulates hippocampus dependent learning and memory.This paper mainly examined the effect of D1R dysfunction in the LHb on the emotional behaviors, fear memory, aversive learning memory, synaptic plasticity of hippocampus CA1 and phosphorylation of GluRl subunit with behavioral, electrophysiological and molecular biological methods in male SD rats.We found that:1) Behavioral:Rat was detected in open field, elevated plus maze, forced swimming, conditioned fear memory and conditioned taste aversion. These results showed that local application of D1R agonist SKF-38393 or antagonist SCH-23390 respectively in the LHb increased rats’anxiety level, impaired the acquisitionof context fear memory and the acquisition and retrieval of aversive learning memory but could produce antidepressant like behaviors.2) Electrophysiologial:In awake, freely moving rat, we used electrophysiological recording techniques to study the effect of local application of D1R agonist or antagonist in the LHb on hippocampal CA1 synaptic transmission. It was found that high frequence stimulation could induce synaptic potention at least one hour in Schaeffer collateral-CA1 pathway of hippocampus. Compared with control group, the amplitude of LTP in drug group was impaired.3) Molecullar:Western blot study found that local application of D1R agonist or antagonist in the LHb decreased phosphorylation of GluRl subunit at ser845&ser831 in the hippocampus.Take together:local application of D1R agonist or antagonist in the LHb increased rats’anxiety level, produced antidepressant like behaviors, impaired the acquisition and retrieval of rats’memory, decreased phosphorylation of GluRl subunit and the amplitude of LTP in the hippocampus. Our results suggestted that how to use a new functional loop regulates emotion and cognition by dopamine system.