| Calcium/calmodulin-dependent protein kinaseⅡ(CaMKⅡ) plays an important role in synaptic plasticity, learning and memory. The a andβCaMKⅡare two main isoforms of CaMKⅡin the forebrain. The roles of aCaMKⅡin synaptic plasticity have been studied extensively; however, the information regarding that ofβCaMKⅡis rare. This experiment was designed to investigate the effects of theβCaMKⅡon the synaptic plasticity in dentate gyrus (DG) and the hippocampus-related memory by using the transgenic mice in which the overexpression of PCaMKⅡis restricted to the DG area. In vitro electrophysiological technique and behavioral method were employed in the present study. The major findings are showed as follows:1. Protein analysis ofβCaMKⅡexpressionWestern bloting analysis showed that the level ofβCaMKⅡprotein in hippocampus was significant higher inβCaMKⅡ-F90G transgenic mice than in wild type mice.2. Investigation of the basic synaptic transmission and basal electrophysiological properties of granule cells in dentate gyrus ofβCaMKⅡ-F90G transgenic miceWe have investigated the basic synaptic transmission function of Medial Perforant Pathway (MPP) and Lateral Perforant Pathway (LPP) inβCaMKⅡ-F90G transgenic mice by using the brain slice field potential recording technique. The results from the paired pulse depression and paired pulse facilitation curves suggest that presynaptic function is normal inβCaMKⅡ-F90G transgenic mice.To study the effects ofβCaMKⅡon granule cells'basal electrophysiological properties, we use the brain slice patch clamp technique to evaluate the resting membrane potential (Vm) and voltage-current plot of dentate gyrus granule cells of βCaMKⅡ-F90G transgenic mice and wild-type mice. The results showed that there were no significant differences between wild-type and transgenic mice in all these respects. So high expression ofβCaMKⅡdid not change the basal electrophysiological properties of dentate gyrus granule cells.3. Investigation of long-term synaptic plasticity at MPP and LPP synapses inβCaMKⅡ-F90G transgenic miceBy employing the field potential recording technique, we have studied the effect ofβCaMKⅡoverexpression specific in DG on synaptic plasticity in entorhinal cortex input synapses onto the MPP and LPP. The results showed that the low frequency stimulation (1 Hz,15 min and 3 Hz,5 min) failed to induce the robust long-term depression at medial perforant pathway inβCaMKⅡ-F90G transgenic slices as did in wild type slices. Furthermore,0.5μM NM-PP1, a specific inhibitor ofβCaMKⅡ-F90G could restore the LTD deficit in the transgenic slices. These results suggest that overexpression of PCaMKII impairs the LTD inβCaMKⅡ-F90G transgenic slices, and NM-PP1 treatment can reverse this deficit in transgenic slices. When we changed the stimulation frequency to 5Hz,3min or lOHz,1.5min, there is also significant difference in synaptic plasticity at MPP pathway between two groups, but the relation is reversed. The results indicate that overexpression ofβCaMKⅡsubunit may weaken the synaptic plasticity in DG area. Besides, we can get the same conclusion from the result of Lateral Perforant Pathway.4. The general activity and the hippocampus-related memory ofβCaMKⅡ-F90G transgenic miceSome behavioral tasks such as open field and light-dark transition were used to study the general activity and emotional behavior ofβCaMKⅡ-F90G transgenic mice. No significant difference has been observed in the locomotor activity, exploratory ability and emotion between transgenic mice and wild-type mice. To investigate the relationship between overexpression ofβCaMKⅡin DG area and hippocampus-related learning memory function, we used passive avoidance test to study the associative memory and extinction process in mice. TheβCaMKⅡ-F90G mice exhibited impaired performances, which was reversed by oral treatment of 5μM NM-PP1. These results indicate that the overexpression ofβCaMKⅡin DG may influence the behavior flexibility in mice. Our research is helpful to understand the close relationship between synaptic plasticity and learning memory.These results suggest that overexpression of theβCaMKⅡmay impair the long-term depression and the hippocampus-related memory without effect on the presynaptic function in DG area or basic electrophysiological properties of granule cells.
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