Visualization of the distribution of autophosphorylated calcium/calmodulin-dependent protein kinase II after tetanic stimulation in the CA1 area of the hippocampus

Autophosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) at threonine-286 produces Ca2+-independent kinase activity and has been proposed to be involved in induction of long-term potentiation by tetanic stimulation in the hippocampus. We have used an immunocytochemical method to visualize and quantify the pattern of autophosphorylation of CaMKII in hippocampal slices after tetanization of the Schaffer collateral pathway. Thirty minutes after tetanic stimulation, autophosphorylated CaM kinase II (P-CaMKII) is significantly increased in area CA1 both in apical dendrites and in pyramidal cell somas. In apical dendrites, this increase is accompanied by an equally significant increase in staining for nonphosphorylated CaM kinase II. Thus, the increase in P-CaMKII appears to be secondary to an increase in the total amount of CaMKII. In neuronal somas, however, the increase in P-CaMKII is not accompanied by an increase in the total amount of CaMKII. We suggest that tetanic stimulation of the Schaffer collateral pathway may induce new synthesis of CaMKII molecules in the apical dendrites, which contain mRNA encoding its alpha-subunit. In neuronal somas, however, tetanic stimulation appears to result in long-lasting increases in P-CaMKII independent of an increase in the total amount of CaMKII. Our findings are consistent with a role for autophosphorylation of CaMKII in the induction and/or maintenance of long-term potentiation, but they indicate that the effects of tetanus on the kinase and its activity are not confined to synapses and may involve induction of new synthesis of kinase in dendrites as well as increases in the level of autophosphorylated kinase

Tetanic Stimulation Leads to Increased Accumulation of Ca^(2+)/Calmodulin-Dependent Protein Kinase II via Dendritic Protein Synthesis in Hippocampal Neurons

mRNA for the ɑ-subunit of CaMKII is abundant in dendrites of neurons in the forebrain (Steward, 1997). Here we show that tetanic stimulation of the Schaffer collateral pathway causes an increase in the concentration of ɑ-CaMKII in the dendrites of postsynaptic neurons. The increase is blocked by anisomycin and is detected by both quantitative immunoblot and semiquantitative immunocytochemistry. The increase in dendritic ɑ-CaMKII can be measured 100-200 µm away from the neuronal cell bodies as early as 5 min after a tetanus. Transport mechanisms for macromolecules from neuronal cell bodies are not fast enough to account for this rapid increase in distal portions of the dendrites. Therefore, we conclude that dendritic protein synthesis must produce a portion of the newly accumulated CaMKII. The increase in concentration of dendritic CaMKII after tetanus, together with the previously demonstrated increase in autophosphorylated CaMKII (Ouyang et al., 1997), will produce a prolonged increase in steady-state kinase activity in the dendrites, potentially influencing mechanisms of synaptic plasticity that are controlled through phosphorylation by CaMKII

Human memory strength is predicted by theta-frequency phase-locking of single neurons

Learning from novel experiences is a major task of the central nervous system. In mammals, the medial temporal lobe is crucial for this rapid form of learning. The modification of synapses and neuronal circuits through plasticity is thought to underlie memory formation. The induction of synaptic plasticity is favoured by coordinated action-potential timing across populations of neurons. Such coordinated activity of neural populations can give rise to oscillations of different frequencies, recorded in local field potentials. Brain oscillations in the theta frequency range (3–8 Hz) are often associated with the favourable induction of synaptic plasticity as well as behavioural memory. Here we report the activity of single neurons recorded together with the local field potential in humans engaged in a learning task. We show that successful memory formation in humans is predicted by a tight coordination of spike timing with the local theta oscillation. More stereotyped spiking predicts better memory, as indicated by higher retrieval confidence reported by subjects. These findings provide a link between the known modulation of theta oscillations by many memory-modulating behaviours and circuit mechanisms of plasticity

The Effect of Psyllium Hydrocolloid and Cholestyramine on Hepatic Bile Lipid Composition in Man

The effects of a mucoid - psyllium hydrocolloid - and an anion exchange polymercholestryamine - on the total cholesterol, total phospholipid, total bile salt, cholate, chenodeoxycholate, and deoxycholate concentrations of hepatic bile were determined in six post-cholecystectomy patients. Bile was obtained by drainage through an indwelling T-tube, which was clamped except during bile collection. Psyllium hydrocolloid treatment (12 gm/day) for 6 to 29 days had little or no effect on the cholesterol or phospholipid concentration of hepatic bile, but increased the total bile salt pool by gradually increasing the concentration of deoxycholate. Cholestyramine treatment (12 gm/day) for 8 to 12 days had no significant effect on cholesterol, phospholipid or total bile salt concentrations. There was a significant increase in the tri- to di-hydroxy bile salt ratio due to decreases in chenodeoxycholate and deoxycholate concentrations. The ratio of taurine to glycine conjugates decreased because of reductions in concentrations of taurine conjugates and compensating increases in glycine conjugates. The influence of these changes on bile micelle stability and cholesterol solubility is discussed. It is concluded that the changes effected by psyllium hydrocolloid may result in more stable bile micelles and greater cholesterol solubility. No definite conclusions can be reached with respect to cholestyramine\u27s effects

Do closed survey questions over-estimate public perceptions of food risks?

In this paper we show that the widely accepted methodology for the assessment of risk perception – Likert type survey questions featuring a set of risks with fixed response alternatives measuring the extent of worry or concern – may over-estimate food risk perception. Using a European representative sample survey (n=26,961) that included an open-ended question asking about problems and risks with food and eating, followed by a battery of closed questions assessing food risk perception we find a similar ranking of perceived food risks across the two methods. Across Europe the five priority concerns are chronic food related illness; food origins and quality; acute food related illness; chemical contamination, and adulteration of food. However, the discrepancies between mentioning a risk in the open ended question and the expression of worry about risks in the closed question are substantial. Of those who did not mention a specific risk category in the open question, between 60% and 83% (depending on risk category) expressed worry in the closed question. This parallels previous research on the fear of crime, showing that survey responses lead to greatly inflated estimates of the public’s fear of crime than is evidenced by qualitative questioning. It is also consistent with evidence from research on cognitive aspects of survey methodology suggesting that survey questions may frame the respondent’s thinking about an issue. We conclude with recommendations for the use of branched questions in the quantitative elicitation of public perceptions of risk

Managing the Socially Marginalized: Attitudes Towards Welfare, Punishment and Race

Welfare and incarceration policies have converged to form a system of governance over socially marginalized groups, particularly racial minorities. In both of these policy areas, rehabilitative and social support objectives have been replaced with a more punitive and restrictive system. The authors examine the convergence in individual-level attitudes concerning welfare and criminal punishment, using national survey data. The authors\u27 analysis indicates a statistically significant relationship between punitive attitudes toward welfare and punishment. Furthermore, accounting for the respondents\u27 racial attitudes explains the bivariate relationship between welfare and punishment. Thus, racial attitudes seemingly link support for punitive approaches to opposition to welfare expenditures. The authors discuss the implications of this study for welfare and crime control policies by way of the conclusion

A Halomethane thermochemical network from iPEPICO experiments and quantum chemical calculations

Internal energy selected halomethane cations CH3Cl+, CH2Cl2+, CHCl3+, CH3F+, CH2F2+, CHClF2+ and CBrClF2+ were prepared by vacuum ultraviolet photoionization, and their lowest energy dissociation channel studied using imaging photoelectron photoion coincidence spectroscopy (iPEPICO). This channel involves hydrogen atom loss for CH3F+, CH2F2+ and CH3Cl+, chlorine atom loss for CH2Cl2+, CHCl3+ and CHClF2+, and bromine atom loss for CBrClF2+. Accurate 0 K appearance energies, in conjunction with ab initio isodesmic and halogen exchange reaction energies, establish a thermochemical network, which is optimized to update and confirm the enthalpies of formation of the sample molecules and their dissociative photoionization products. The ground electronic states of CHCl3+, CHClF2+ and CBrClF2+ do not confirm to the deep well assumption, and the experimental breakdown curve deviates from the deep well model at low energies. Breakdown curve analysis of such shallow well systems supplies a satisfactorily succinct route to the adiabatic ionization energy of the parent molecule, particularly if the threshold photoelectron spectrum is not resolved and a purely computational route is unfeasible. The ionization energies have been found to be 11.47 ± 0.01 eV, 12.30 ± 0.02 eV and 11.23 ± 0.03 eV for CHCl3, CHClF2 and CBrClF2, respectively. The updated 0 K enthalpies of formation, ∆fHo0K(g) for the ions CH2F+, CHF2+, CHCl2+, CCl3+, CCl2F+ and CClF2+ have been derived to be 844.4 ± 2.1, 601.6 ± 2.7, 890.3 ± 2.2, 849.8 ± 3.2, 701.2 ± 3.3 and 552.2 ± 3.4 kJ mol–1, respectively. The ∆fHo0K(g) values for the neutrals CCl4, CBrClF2, CClF3, CCl2F2 and CCl3F and have been determined to be –94.0 ± 3.2, –446.6 ± 2.7, –702.1 ± 3.5, –487.8 ± 3.4 and –285.2 ± 3.2 kJ mol–1, respectively