Hippocampal CA1 pyramidal cells receive two major excitatory synaptic inputs via the Schaffer collateral (SC) and temporoammonic (TA) pathways. Nicotine promotes induction of long-term potentiation (LTP) in the SC path; however, it is not known whether the modulatory effect of nicotine on LTP induction is pathway-specific. Here we show that nicotine suppresses LTP induction in the TA path. Interestingly, these opposing effects of nicotine were absent or greatly reduced in alpha2 nicotinic acetylcholine receptor (nAChR)-knockout (KO) mice, suggesting that an alpha2-containing nAChR subtype mediates these effects. Optical imaging with a voltage-sensitive dye revealed significantly stronger membrane depolarization in the presence of nicotine in the SC path, facilitating spread of excitatory neural activity along both the somatodendritic and the CA1 proximodistal axes. These effects of nicotine were also absent in alpha2 nAChR-KO mice, suggesting that the enhanced optical signal is related to the nicotine-induced facilitation of LTP induction. In contrast, in the TA path nicotine terminated depolarization more quickly and increased the delayed hyperpolarization in the termination zone of the TA path input. These inhibitory effects of nicotine were absent in alpha2 nAChR-KO mice and, thus, most probably underlie the nicotine-induced suppression of LTP induction. Our results suggest that nicotine influences the local balance between excitation and inhibition, gates LTP, and directs information flow through the hippocampal circuits via the activation of alpha2* nAChRs. These effects of nicotine may represent the cellular basis of nicotine-mediated cognitive enhancement.
Aim: α2 nAChR subunit mRNA expression in mice is most intense in the olfactory bulbs and interpeduncular nucleus. We aimed to investigate the properties of α2* nAChRs in these mouse brain regions. Methods: α2 nAChR subunit-null mutant mice were engineered. Pharmacological and immunoprecipitation studies were used to determine the composition of α2 subunit-containing (α2*) nAChRs in these two regions. Results: [ 125 I]Epibatidine (200 pmol/L) autoradiography and saturation binding demonstrated that α2 deletion reduces nAChR expression in both olfactory bulbs and interpeduncular nucleus (by 4.8±1.7 and 92±26 fmol·mg -1 protein, respectively). Pharmacological characterization using the β2-selective drug A85380 to inhibit [ 125 I]epibatidine binding proved inconclusive, so immunoprecipitation methods were used to further characterize α2* nAChRs. Protocols were established to immunoprecipitate β2 and β4 nAChRs. Immunoprecipitation specificity was ascertained using tissue from β2-and β4-null mutant mice, and efficacy was good (>90% of β2* and >80% of β4* nAChRs were routinely recovered). Conclusion:Immunoprecipitation experiments indicated that interpeduncular nucleus α2* nAChRs predominantly contain β2 subunits, while those in olfactory bulbs contain mainly β4 subunits. In addition, the immunoprecipitation evidence indicated that both nuclei, but especially the interpeduncular nucleus, express nAChR complexes containing both β2 and β4 subunits.
In 1977, Massachusetts implemented a requirement that Medicaid recipients obtain a second surgical opinion before elective surgery. Using consultants' reports and surveys, we assessed the initial year's results in metropolitan Boston. Of 2060 Medicaid patients originally advised to undergo one of eight elective surgical procedures, 1591 (77.2 per cent) participated in the mandatory second-opinion consultation program, 10.5 per cent received approval for surgery without a second opinion because of clear indications such as cancer, and 12.3 per cent did not keep or accept appointments for a second opinion. Of the 1591 patients who participated, 88.7 per cent were given second opinions in favor of surgery, and 11.3 per cent were advised against surgery. Eight-two of the 180 patients advised not to have surgery sought a third opinion; the negative second opinion was reversed by the third consultant in 57 of these cases (69.5 per cent). Thus, surgery was rejected by a second or third consultant for only 7.7 per cent of the participating patients. We conclude that many negative second opinions are due to honest disagreement about indications for surgery. We also estimate that although the second-opinion program may produce only modest direct savings in Medicaid expenditures, it probably offers important improvements in the quality of health care.
school has been described by Cotton, Patterson, Browne, and Cotton (1979) as a &dquo;marginal role&dquo; that is &dquo;characterized by conflicting reference and peer group pressures.&dquo; Studies of marginality have focused on the anxiety, conflict, and stress that are incurred by the principal when operating between groups with conflicting interests. To be an effective principal it is important to maintain a marginal position; that is, not to become aligned with one interest group.To maintain marginality, a principal must understand the demands, goals, needs, and motivations of each pressure group. The principal must reconcile these with his or her own ethical standards and attempt to maintain harmony. Considering the varieties of ethical thought, and the disparate attitudes toward special education programs, the principal's task is not an easy one.As the principal functions in the &dquo;marginal role&dquo; as the most visible school administrator to parents, the ultimate authority to faculty, staff, and students, interpreter and implementer of district policy, arbitrator, role model, and the one who is responsible for the establishment and maintenance of the educational climate of the school, it is the principal who must ultimately deal with the various legal and ethical issues surrounding the implementation of P.L. 94-142.Implementing P.L. 94-142In some cases, there is friction and misunderstanding between regular and special education teachers. Regular class teachers sometimes resent having to take a special youngster into a class of 25-30 pupils when the special education teacher might only have 7-12 students. Regular class teachers might also be asked to collect information, assign points, and perhaps take the time to write a short note describing a special student's behavior when placed in the regular classroom.This is often interpreted as unrealistic and unjust. The special education teacher might take a stance that the handicapped student has worth and deserves every chance to succeed in the &dquo;main-stream&dquo; of the school. The regular classroom teacher might refer to the posture of wanting to do the &dquo;greatest good for the greatest number.&dquo;The classroom teacher might indicate that much time is being taken away from the 25-30 nonhandicapped students and that lesson presentations are taking at University of Manitoba Libraries on June 21, 2015 bul.sagepub.com Downloaded from
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