Chronic constant light-induced hippocampal late-phase long-term potentiation impairment in vitro is attenuated by antagonist of D1/D5 receptors.

Previous study reported that chronic constant light exposure caused hippocampus-dependent long-term memory deficit. However, the underlying cellular mechanism of this impairment is still unclear. Multiple lines of evidence indicated that long-term potentiation (LTP) is a cellular model for memory formation. Here we found that, by recording of field excitatory postsynaptic potential (fEPSP) in vitro, chronic constant light (CCL, 3 weeks) exposure impaired the late long-term potentiation (L-LTP), but not early long-term potentiation (E-LTP) and basal transmission in Schaffer collateral (SC)-CA1 synapses of hippocampal slices from rats. Because L-LTP depends on D1/D5 receptors, we examined whether interference of D1/D5 receptors can modulate L-LTP of CCL rats. Bath application of D1/D5 receptors antagonist SCH23390 (1µM) blocked L-LTP in control rats and attenuated the impaired L-LTP in CCL rats. In contrast, pre-incubation of D1/D5 receptors agonist SKF38393 (25µM) occluded further L-LTP in control rats while exacerbated the L-LTP impairment in CCL rats. These results suggested that CCL-induced L-LTP impairment can be modulated by D1/D5 receptors. Our findings may contribute to the further understanding of synaptic plasticity mechanism underlying hippocampal long-term memory impairment induced by circadian rhythm disruption.

Whole-scale neurobehavioral assessments of photothrombotic ischemia in freely moving mice.

BACKGROUND: Neurobehavioral assessments have been considered as an essential component of preclinical research in ischemic stroke. However, real-time neurobehavioral evaluation is seldom applied during ischemia induction as it is usually accompanied with anesthesia. NEW METHOD: We induced photothrombosis in freely moving mice after one-week recovery from cannula implantation surgeries. After rose bengal (RB) injection (100 mg/kg, i.p.), photothrombosis was induced in freely moving mice by 473 nm laser irradiation through the cannulas implanted into unilateral primary motor cortex beforehand. Mice received nimodipine (15 mg/kg, i.p.), a widely used anti-ischemic agent, or vehicle before irradiation. Motor coordination and equilibrium were evaluated by rotarod and rung walk tests throughout the whole process of ischemia. Endurance capacity was assessed by treadmill at 1 day and 7 days after irradiation. Mice were decapitated at different time points post irradiation for TTC (2,3,5-triphenyltetrazolium chloride) staining. RESULTS: Consistent with the results of TTC staining, motor deficits firstly occurred at 15-min post irradiation and aggravated 1-day later, while the capacity improved 3-days later and partially recovered 7-days post irradiation. And, the recovery process was accelerated by nimodipine application. COMPARISON WITH EXISTING METHODS: This method established a precise linkage between focal brain ischemia development and neurobehavioral deficits throughout a full scale of photothrombosis, which avoided the confounding factors of anesthetics and surgeries on neurobehavioral assessments, as infarct was induced in freely moving mice. CONCLUSIONS: This method with high temporal and spatial resolution will be an optimal model for neurobehavioral evaluation in preclinical anti-ischemic drug screening.