Derrick. Long-term potentiation in direct perforant path projections to the hippocampal CA3 region in vivo. J Neurophysiol 87: 669 -678, 2002; 10.1152/jn.00938.2000. The perforant path constitutes the primary projection system relaying information from the neocortex to the hippocampal formation. Long-term synaptic potentiation (LTP) in the perforant path projections to the dentate gyrus is well characterized. However, surprisingly few studies have addressed the mechanisms underlying LTP induction in the direct perforant path projections to the hippocampus. Here we investigate the role of N-methyl-D-aspartate (NMDA) and opioid receptors in the induction of LTP in monosynaptic medial and lateral perforant path projections to the CA3 region in adult pentobarbital sodium-anesthetized rats. Similar to LTP observed at the medial perforant path-dentate gyrus synapse, medial perforant path-CA3 synapses display LTP that is blocked by both local and systemic administration of the competitive NMDA receptor antagonist (Ϯ)-3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid [(Ϯ)-CPP]. By contrast, LTP induced at the lateral perforant path-CA3 synapses is not blocked by either local or systemic administration of this NMDA receptor antagonist. The induction of LTP at lateral perforant path-CA3 synapses, which is blocked by the opioid receptor antagonist naloxone, is also blocked by the selective mu () opioid receptor antagonist Cys 2 -Tyr 3 -Orn 5 -Pen 7 -amide (CTOP), but not the selective delta (␦) opioid receptor antagonist naltrindole (NTI). CTOP was without effect on the induction of medial perforant path-CA3 LTP. The selective sensitivity of lateral perforant path-CA3 LTP to -opioid receptor antagonists corresponds with the distribution of -opioid receptors within the stratum lacunosum-moleculare of area CA3 where perforant path projections to CA3 terminate. These data indicate that both lateral and medial perforant path projections to the CA3 region display LTP, and that LTP induction in medial and lateral perforant path-CA3 synapses are differentially sensitive to NMDA receptor and -opioid receptor antagonists. This suggests a role for opioid, but not NMDA receptors in the induction of LTP at lateral perforant path projections to the hippocampal formation.
The role of beta-endorphin as a possible mediator in the reinforcing properties of opiates was investigated using a conditioned place preference paradigm. Heroin, a synthetic opiate known to have reinforcing properties, produced a strong preference for an environment previously paired with heroin injection at all doses tested (0.25, 0.5, 1.0, 2.0 mg/kg SC). No such place preference was observed following saline injections. Rats also showed dose-dependent place preference for the environment paired with beta-endorphin when injected intracerebroventricularly (significant dose was 2.5 micrograms). At higher doses (5.0 and 10.0 micrograms) rats showed no preference for the paired environment, but were catatonic. Pretreatment with naloxone (0.04, 0.2, 1.0 mg/kg SC) attenuated the rewarding effect of beta-endorphin (2.5 micrograms) at all doses tested. The lowest dose of naloxone which had no aversive effect when tested alone could also significantly block the positive effect of beta-endorphin. The reinforcing dose of beta-endorphin (2.5 micrograms) also produced an increase in locomotor activity, when tested in photocell cages. This suggests that the hyperactivity induced by beta-endorphin may contribute to the preference for an environment previously paired with the same drug. The reinforcing effect of beta-endorphin is most probably mediated by the mu and/or delta opioid subtype receptor, since beta-endorphin has a high affinity for these receptors. These results demonstrate positive reinforcing properties of beta-endorphin in the central nervous system.
Long-term cognitive impairments are a feared consequence of therapeutic cranial irradiation in children as well as adults. Studies in animal models suggest that these deficits may be associated with a decrease in hippocampal granule cell proliferation and survival. In the present study the authors examined whether whole brain irradiation would affect trace fear conditioning, a hippocampal-dependent task. Preadolescent (postnatal Day 21, PD 21), adolescent (PD 50), and postadolescent (PD 70) rats received single doses of 0 Gray (Gy), 0.3 Gy, 3 Gy, or 10 Gy whole brain irradiation. Three months after radiation treatment, a significant dose-dependent decrease in bromo-deoxyuridine positive cells was observed. Irradiation produced a dose-dependent decrease in freezing in response to the conditioned stimulus in all age groups. Interestingly, the authors found no differences in context freezing between irradiated and control groups. Further, there were no differences in delay fear memories, which are independent of hippocampus function. Our results strongly indicate that irradiation impairs associative memories dependent on hippocampus and this deficit is accompanied by a decrease in granule cell neurogenesis indicating that these cells may be involved in normal hippocampal memory function.
The trend in power electronic applications is to reach higher power density and higher efficiency. Currently, the wide band-gap devices such as Silicon Carbide MOSFET (SiC MOSFET) are of great interest because they can work at higher switching frequency with low losses. The increase of the switching speed in power devices leads to high power density systems. However, this can generate problems such as overshoots, oscillations, additional losses and electromagnetic interference (EMI). In this paper, a novel active gate driver (AGD) for improving the SiC MOSFET switching trajectory with high performance is presented. The AGD is an open-loop control system and its principle is based on gate energy decrease with a gate resistance increment during the Miller Plateau effect on gatesource voltage. The proposed AGD has been designed and validated through experimental tests for high-frequency operation. Moreover, an EMI discussion and a performance analysis were realized for the AGD. The results show that the AGD can reduce the overshoots, oscillations and losses without compromising the EMI. Besides, the AGD can control the turn-on and turn-off transitions separately and it is suitable for working with asymmetrical supplies required by SiC MOSFETs.
The dorsal CA3 region of the hippocampus is unique in its connectivity, sensitivity to neurotoxic lesions, and its ability to encode and retrieve episodic memories. Computational models of the CA3 region predict that blocking mossy-fiber and/or perforant path activity to CA3 would cause impairments in learning and recall of spatial memory, respectively. Because the CA3 region contains -opioid receptors and receives inputs from the mossy-fiber and lateral perforant pathways, both of which contain and release opioid peptides, we tested the hypothesis that inactivating -opioid receptors in the CA3 region would cause spatial learning and memory impairments and retrieval deficits. In this study, male Sprague Dawley rats were trained in a Morris water maze after a single bilateral intrahippocampal injection of either saline or the selective and irreversible -opioid receptor antagonist -funaltrexamine (-FNA) into area CA3. We found that -opioid receptor binding decreased 24 hr after -FNA injection and returned to control levels 11 d after injection. Injections of -FNA into the CA3 region, but not into the ventricles, caused a significant impairment in the acquisition of spatial learning without causing sensory or motor deficits. New learning was not affected once -opioid receptor levels replenished (Ͼ11 d after injection). In pretrained animals, -FNA significantly impaired spatial memory retrieval and new (reversal) learning. These data are consistent with theoretical models of CA3 function and suggest that CA3 -opioid receptors play an important role in the acquisition and retrieval of spatial memory.
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