Memory is stored in neural networks via changes in synaptic strength mediated in part by NMDA-dependent long-term potentiation (LTP). There is evidence that entorhinal cortex enables neocortical neuroplasticity through cholecystokinin (CCK)-containing neocortical projections. Here we show that a CCK B antagonist blocks high-frequency stimulation (HFS)-induced LTP in the auditory cortex, whereas local infusion of CCK induces LTP. CCK -/- mice lacked neocortical LTP and showed deficits in a cue-cue associative learning paradigm; administration of CCK rescued associative learning. HFS of CCK-containing entorhino-neocortical projection neurons in anesthetized mice enabled cue-cue associative learning. Furthermore, when one cue was pre-conditioned to footshock, the mouse showed a freezing response to the other cue, indicating that the mice had formed an association. HFS-induced neocortical LTP was completely blocked by either NMDA antagonist or CCK-BR antagonist, while application of either NMDA or CCK induced LTP after low-frequency stimulation (LFS). Moreover, in the presence of CCK LTP was still induced, even after blockade of NMDA receptors. Local application of NMDA induced CCK release in the neocortex. To identify how NMDA receptor switches LTP, a stimulation protocol of 25 pulse-pairs was adopted to replace HFS; NMDA-dependent LTP was induced with the inter-pulse intervals between 10 and 100 ms, but not with those of 5 and 200 ms. LTP-mediated plasticity was linked to localization of the NMDA receptor subunit NR2a on cortical CCK terminals originating in the entorhinal cortex. These novel findings suggest that presynaptic NMDA receptors on CCK terminals control the release of CCK, which enables neocortical LTP and formation of cue-cue associative memory. One Sentence Summary Presynaptic NMDA receptors switches the release of CCK from entorhinal neurons, which enables neocortical LTP and formation of sound-sound associative memory.

OBJECTIVE:To assess the inhibitory modulation of blood pressure by stimulation of the deep peroneal nerve (DPN) and to determine the involvement of nociceptive fibers in the modulation.METHODS:All the animals were divided into six groups (A-F). The rats in groups A and B received no pretreatment. The rats in groups C and D received subcutaneous injection of capsaicin or control vehicle, respectively, near the DPN for 2 days. Those in groups E and F had the DPN exposed to capsaicin or control vehicle, respectively, for 20 min. Subsequently, pressor responses were induced by stimulation of paraventricular nucleus (PVN) either electrically (groups A and C C-F) or chemically via injection of glutamate (group B). After two stable pressor responses (baseline), all groups were subject to 5-min DPN stimulation followed by PVN stimulation for 10 s. Arterial blood pressure, heart rate, and electrocardiogram were recorded. The pressor response was calculated as the difference in the mean arterial pressure (MAP) before and after PVN stimulation, and changes from baseline in pressor response after DPN stimulation were compared between the groups.RESULTS:Increases of MAP of 22.88±2.18 mm Hg and 20.32±5.25 mm Hg were induced by electrical (group A) or chemical (group B) stimulation of the PVN, respectively. These pressor responses were inhibited by stimulation of the DPN, and the MAP was reduced to 12.00±2.10 mm Hg in group A (n=6, P<0.01) and 7.00±2.85 mm Hg in group B (n=6, P<0.01). Subcutaneous injection of capsaicin (125 mg/kg) near the DPN in group C (n=7) had no effect on the inhibitory effect of DPN stimulation compared with the group D (n=9), and neither did blockade of nociceptive fibers with capsaicin in group E (n=6) compared with group F (n=8).CONCLUSION:Stimulation of the DPN mimicking acupuncture has an inhibitory effect on the pressor response, and the effect is mediated by capsaicin-insensitive afferent fibers in the DPN.

Objective To investigate the response of astrocytes to craniocerebral injury caused by water-sac pressure on rat brain. Methods The water sac entirely inserted into encephalic putamen of rat was filled with sterile physiological saline and maintained its size and pressure for 2 hours.Rats were sacrificed at indicated times and their brain tissue were collected to carry out HE staining and immunohistochemical staining. Results In the 1 h injury group,Glial fibrillary acidic protein(GFAP) positive cells with short pustutes were found around the injury area and most of reactive astrocytes aggregated at wound margin..In the 24 h injury group,the extent of GFAP expression increased and most of positive cells showed larger size of bodies,increscent pustutes and deep staining.Meanwhile,the total number of positive cells increased and aggregated at would margin and injury area.GFAP was expressed in hippocampus cells after 24 h injury.In the 3 d,6 d,and 12 d injury groups,GFAP expression maintained at a high level and these positive cells displayed diverse celluar bodyand pustute shapes.When injured for 12 days,the expression of GFAP was highest and the mount of GFAP positive cells reached a peak. Conclusion The water-bag pressure-caused brain injury model can mimic the pathogenesis of craniocerebral hematoma injury.