Nucleus- and species-specific properties of the slow (<1 Hz) sleep oscillation in thalamocortical neurons.

The slow (<1 Hz) rhythm is an electroencephalogram hallmark of resting sleep. In thalamocortical neurons this rhythm correlates with a slow (<1 Hz) oscillation comprising recurring UP and DOWN membrane potential states. Recently, we showed that metabotropic glutamate receptor activation brings about an intrinsic slow oscillation in thalamocortical neurons of the cat dorsal lateral geniculate nucleus in vitro which is identical to that observed in vivo. The aim of this study was to further assess the properties of this oscillation and compare them with those observed in thalamocortical neurons of three other thalamic nuclei in the cat (ventrobasal complex, medial geniculate body; ventral lateral nucleus) and two thalamic nuclei in rats and mice (lateral geniculate nucleus and ventrobasal complex). Slow oscillations were evident in all of these additional structures and shared several basic properties including, i) the stereotypical, rhythmic alternation between distinct UP and DOWN states with the UP state always commencing with a low-threshold Ca2+ potential, and ii) an inverse relationship between frequency and injected current so that slow oscillations always increase in frequency with hyperpolarization, often culminating in delta (delta) activity at approximately 1-4 Hz. However, beyond these common properties there were important differences in expression between different nuclei. Most notably, 44% of slow oscillations in the cat lateral geniculate nucleus possessed UP states that comprised sustained tonic firing and/or high-threshold bursting. In contrast, slow oscillations in cat ventrobasal complex, medial geniculate body and ventral lateral nucleus thalamocortical neurons exhibited such UP states in only 16%, 11% and 10% of cases, respectively, whereas slow oscillations in the lateral geniculate nucleus and ventrobasal complex of rats and mice did so in <12% of cases. Thus, the slow oscillation is a common feature of thalamocortical neurons that displays clear species- and nuclei-related differences. The potential functional significance of these results is discussed.

Abolition of zolpidem sensitivity in mice with a point mutation in the GABAA receptor gamma2 subunit.

Agonists of the allosteric benzodiazepine site of GABAA receptors bind at the interface of the alpha and gamma subunits. Here, we tested the in vivo contribution of the gamma2 subunit to the actions of zolpidem, an alpha1 subunit selective benzodiazepine agonist, by generating mice with a phenylalanine (F) to isoleucine (I) substitution at position 77 in the gamma2 subunit. The gamma2F77I mutation has no major effect on the expression of GABAA receptor subunits in the cerebellum. The potency of zolpidem, but not that of flurazepam, for the inhibition of [3H]flunitrazepam binding to cerebellar membranes is greatly reduced in gamma2I77/I77 mice. Zolpidem (1 microM) increased both the amplitude and decay of miniature inhibitory postsynaptic currents (mIPSCs) in Purkinje cells of control C57BL/6 (34% and 92%, respectively) and gamma2F77/F77 (20% and 84%) mice, but not in those of gamma2F77I mice. Zolpidem tartrate had no effect on exploratory activity (staircase test) or motor performance (rotarod test) in gamma2I77/I77 mice at doses up to 30 mg/kg (i.p.) that strongly sedated or impaired the control mice. Flurazepam was equally effective in enhancing mIPSCs and disrupting performance in the rotarod test in control and gamma2I77/I77 mice. These results show that the effect of zolpidem, but not flurazepam, is selectively eliminated in the brain by the gamma2F77I point mutation.

Dynamic clamp study of Ih modulation of burst firing and delta oscillations in thalamocortical neurons in vitro.

The dynamic clamp technique was used in thalamocortical neurons of the rat and cat dorsal lateral geniculate nucleus in vitro to investigate the effects of the hyperpolarization-activated cation current, Ih, and of its neuromodulation on burst firing and delta oscillations. Specific block of endogenous Ih using 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)pyridinium chloride (ZD7288) (300 microM) abolished the depolarizing "sag" response to negative current steps, markedly increased the latency and shortened the duration of the low-threshold Ca2+ potentials, and decreased the number of action potentials in the burst evoked by the low-threshold Ca2+ potential. Subsequent introduction of artificial Ih using the dynamic clamp re-instated the "sag" and all the original properties of the low-threshold Ca2+ potential. In the absence of ZD7288, introduction of artificial outward Ih with the intention of abolishing endogenous Ih removed the depolarizing "sag" and produced similar effects on the low-threshold Ca2+ potentials as those observed during the pharmacological block of Ih. Application of ZD7288 to thalamocortical neurons displaying delta oscillations led to a reduction in the voltage range of their existence or to a complete cessation of this behaviour. A subsequent introduction of artificial Ih re-enabled the generation of delta oscillations. In the presence of ZD7288, physiologically relevant positive shifts in the voltage-dependence of artificial Ih increased the amplitude and duration of the low-threshold Ca2+ potential and increased the likelihood of delta oscillations while negative shifts had opposite effects. These results highlight the important difference between the dependence of burst firing and oscillations on membrane potential and their dependence on the properties of Ih, and demonstrate that the modulation by Ih of low-threshold Ca2+ potentials and burst firing in thalamocortical neurons, as well as the ability of these neurons to generate delta oscillations, is more elaborate than previously described.

Somatostatin inhibits GABAergic transmission in the sensory thalamus via presynaptic receptors.

The action of somatostatin on GABA-mediated transmission was investigated in cat and rat thalamocortical neurons of the dorsal lateral geniculate nucleus and ventrobasal thalamus in vitro. In the cat thalamus, somatostatin (10 microM) had no effect on the passive membrane properties of thalamocortical neurons and on the postsynaptic response elicited in these cells by bath or iontophoretic application of (+/-)baclofen (5-10 microM) or GABA, respectively. However, somatostatin (1-10 microM) decreased by a similar amount (45-55%) the amplitude of electrically evoked GABA(A) and GABA(B) inhibitory postsynaptic potentials in 71 and 50% of neurons in the lateral geniculate and ventrobasal nucleus, respectively. In addition, the neuropeptide abolished spontaneous bursts of GABA(A) inhibitory postsynaptic potentials in 85% of kitten lateral geniculate neurons, and decreased (40%) the amplitude of single spontaneous GABA(A) inhibitory postsynaptic potentials in 87% of neurons in the cat lateral geniculate nucleus. Similar results were obtained in the rat thalamus. Somatostatin (10 microM) had no effect on the passive membrane properties of thalamocortical neurons in this species, or on the outward current elicited by puff-application of (+/-)baclofen (5-10 microM). However, in 57 and 22% of neurons in the rat lateral geniculate and ventrobasal nuclei, respectively, somatostatin (1 microM) reduced the frequency, but not the amplitude, of miniature GABA(A) inhibitory postsynaptic currents by 31 and 37%, respectively. In addition, the neuropeptide (1 microM) decreased the amplitude of evoked GABA(A) inhibitory postsynaptic currents in 20 and 55% of rat ventrobasal neurons recorded in normal conditions and during enhanced excitability, respectively: this effect was stronger on bursts of inhibitory postsynaptic currents(100% decrease) than on single inhibitory postsynaptic currents (41% decrease). These results demonstrate that in the sensory thalamus somatostatin inhibits GABA(A)- and GABA(B)-mediated transmission via a presynaptic mechanism, and its action is more prominent on bursts of GABAergic synaptic currents/potentials.

Properties and origin of spikelets in thalamocortical neurones in vitro.

Spikelets, or fast prepotentials as they are frequently referred to, are a common feature of the electrophysiology of central neurones and are invariably correlated with the presence of electrotonic coupling via gap junctions. Here we report that in the presence of the metabotropic glutamate receptor agonists, trans-ACPD or DHPG, thalamocortical neurones of the cat dorsal lateral geniculate nucleus maintained in vitro exhibit stereotypical spikelets that possess similar properties to those described in other brain areas. These spikelets were routinely observed in the presence of antagonists of fast chemical synaptic transmission, were resistant to the application of a variety of voltage-dependent Ca(2+) channel blockers but were abolished by tetrodotoxin. In addition, spikelets were reversibly blocked by the putative gap junction blocker carbenoxolone and were nearly always accompanied by dye-coupling. These results indicate that thalamocortical neurones may be electrotonically coupled via gap junctions with spikelets representing attenuated action potentials from adjoining cells. We suggest that the presence of electrotonic communication between thalamocortical neurones would have major implications for the understanding of both physiological (Steriade et al., 1993; Sillito et al., 1994; Alonso et al., 1996; Neuenschwander and Singer, 1996; Weliky and Katz, 1999) and pathological (Steriade and Contreras, 1995; Pinault et al., 1998) synchronised electrical activity in the thalamus.

Backpropagation of the delta oscillation and the retinal excitatory postsynaptic potential in a multi-compartment model of thalamocortical neurons.

Uniform and non-uniform somato-dendritic distributions of the ion channels carrying the low-threshold Ca(2+) current (I(T)), the hyperpolarization-activated inward current (I(h)), the fast Na(+) current (I(Na)) and the delayed rectifier current (I(K)) were investigated in a multi-compartment model of a thalamocortical neuron for their suitability to reproduce the delta oscillation and the retinal excitatory post-synaptic potential recorded in vitro from the soma of thalamocortical neurons. The backpropagation of these simulated activities along the dendritic tree was also studied. A uniform somato-dendritic distribution of the maximal conductance of I(T) and I(K) (g(T) and g(K), respectively) was sufficient to simulate with acceptable accuracy: (i) the delta oscillation, and its phase resetting by somatically injected current pulses; as well as (ii) the retinal excitatory postsynaptic potential, and its alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate and/or N-methyl-D-aspartate components. In addition, simulations where the dendritic g(T) and g(K) were either reduced (both by up to 34%) or increased (both by up to 15%) of their respective value on the soma still admitted a successful reproduction of the experimental activity. When the dendritic distributions were non-uniform, models where the proximal and distal dendritic g(T) was up to 1.8- and 1. 2-fold larger, respectively, than g(T(s)) produced accurate simulations of the delta oscillation (and its phase resetting curves) as well as the synaptic potentials without need of a concomitant increase in proximal or distal dendritic g(K). Furthermore, an increase in proximal dendritic g(T) and g(K) of up to fourfold their respective value on the soma resulted in acceptable simulation results. Addition of dendritic Na(+) channels to the uniformly or non-uniformly distributed somato-dendritic T-type Ca(2+) and K(+) channels did not further improve the overall qualitative and quantitative accuracy of the simulations, except for increasing the number of action potentials in bursts elicited by low-threshold Ca(2+) potentials. Dendritic I(h) failed to produce a marked effect on the simulated delta oscillation and the excitatory postsynaptic potential. In the presence of uniform and non-uniform dendritic g(T) and g(K), the delta oscillation propagated from the soma to the distal dendrites with no change in frequency and voltage-dependence, though the dendritic action potential amplitude was gradually reduced towards the distal dendrites. The amplitude and rising time of the simulated retinal excitatory postsynaptic potential were only slightly decreased during their propagation from their proximal dendritic site of origin to the soma or the distal dendrites. These results indicate that a multi-compartment model with passive dendrites cannot fully reproduce the experimental activity of thalamocortical neurons, while both uniform and non-uniform somato-dendritic g(T) and g(K) distributions are compatible with the properties of the delta oscillation and the retinal excitatory postsynaptic potential recorded in vitro from the soma of these neurons. Furthermore, by predicting the existence of backpropagation of low-threshold Ca(2+) potentials and retinal postsynaptic potentials up to the distal dendrites, our findings suggest a putative role for the delta oscillation in the dendritic processing of neuronal activity, and support previous hypotheses on the interaction between retinal and cortical excitatory postsynaptic potentials on thalamocortical neuron dendrites.

Cholecystokinin-immunopositive basket and Schaffer collateral-associated interneurones target different domains of pyramidal cells in the CA1 area of the rat hippocampus.

Two types of GABAergic interneurone are known to express cholecystokinin-related peptides in the isocortex: basket cells, which preferentially innervate the somata and proximal dendrites of pyramidal cells; and double bouquet cells, which innervate distal dendrites and dendritic spines. In the hippocampus, cholecystokinin immunoreactivity has only been reported in basket cells. However, at least eight distinct GABAergic interneurone types terminate in the dendritic domain of CA1 pyramidal cells, some of them with as yet undetermined neurochemical characteristics. In order to establish whether more than one population of cholecystokinin-expressing interneurone exist in the hippocampus, we have performed whole-cell current clamp recordings from interneurones located in the stratum radiatum of the hippocampal CA1 region of developing rats. Recorded neurones were filled with biocytin to reveal their axonal targets, and were tested for the presence of pro-cholecystokinin immunoreactivity. The results show that two populations of cholecystokinin-immunoreactive interneurones exist in the CA1 area (n=15 positive cells). Cholecystokinin-positive basket cells (53%) preferentially innervate stratum pyramidale and adjacent strata oriens and radiatum. A second population of cholecystokinin-positive cells, previously described as Schaffer collateral-associated interneurones [Vida et al. (1998) J. Physiol. 506, 755-773], have axons that ramify almost exclusively in strata radiatum and oriens, overlapping with the Schaffer collateral/commissural pathway originating from CA3 pyramidal cells. Two of seven of the Schaffer collateral-associated cells were also immunopositive for calbindin. Soma position and orientation in stratum radiatum, the number and orientation of dendrites, and the passive and active membrane properties of the two cell populations are only slightly different. In addition, in stratum radiatum and its border with lacunosum of perfusion-fixed hippocampi, 31.6+/-3.8% (adult) or 26.8+/-2.9% (postnatal day 17-20) of cholecystokinin-positive cells were also immunoreactive for calbindin. Therefore, at least two populations of pro-cholecystokinin-immunopositive interneurones, basket and Schaffer collateral-associated cells, exist in the CA1 area of the hippocampus, and are probably homologous to cholecystokinin-immunopositive basket and double bouquet cells in the isocortex. It is not known if the GABAergic terminals of double bouquet cells are co-aligned with specific glutamatergic inputs. However, in the hippocampal CA1 area, it is clear that the terminals of Schaffer collateral-associated cells are co-stratified with the glutamatergic input from the CA3 area, with as yet unknown functional consequences. The division of the postsynaptic neuronal surface by two classes of GABAergic cell expressing cholecystokinin in both the hippocampus and isocortex provides further evidence for the uniform synaptic organisation of the cerebral cortex.

Restructuring VA ambulatory care and medical education: the PACE model of primary care.

The Veterans Health Administration (VHA) Western Region and associated medical schools formulated a set of recommendations for an improved ambulatory health care delivery system during a 1988 strategic planning conference. As a result, the Department of Veterans Affairs (VA) Medical Center in Sepulveda, California, initiated the Pilot (now Primary) Ambulatory Care and Education (PACE) program in 1990 to implement and evaluate a model program. The PACE program represents a significant departure from traditional VA and non-VA academic medical center care, shifting the focus of care from the inpatient to the outpatient setting. From its inception, the PACE program has used an interdisciplinary team approach with three independent global care firms. Each firm is interdisciplinary in composition, with a matrix management structure that expands role function and empowers team members. Emphasis is on managed primary care, stressing a biopsychosocial approach and cost-effective comprehensive care emphasizing prevention and health maintenance. Information management is provided through a network of personal computers that serve as a front end to the VHA Decentralized Hospital Computer Program (DHCP) mainframe. In addition to providing comprehensive and cost-effective care, the PACE program educates trainees in all health care disciplines, conducts research, and disseminates information about important procedures and outcomes. Undergraduate and graduate trainees from 11 health care disciplines rotate through the PACE program to learn an integrated approach to managed ambulatory care delivery. All trainees are involved in a problem-based approach to learning that emphasizes shared training experiences among health care disciplines. This paper describes the transitional phases of the PACE program (strategic planning, reorganization, and quality improvement) that are relevant for other institutions that are shifting to training programs emphasizing primary and ambulatory care.

Loss of zolpidem efficacy in the hippocampus of mice with the GABAA receptor gamma2 F77I point mutation.

Zolpidem is a hypnotic benzodiazepine site agonist with some gamma-aminobutyric acid (GABA)(A) receptor subtype selectivity. Here, we have tested the effects of zolpidem on the hippocampus of gamma2 subunit (gamma2F77I) point mutant mice. Analysis of forebrain GABA(A) receptor expression with immunocytochemistry, quantitative [(3)H]muscimol and [(35)S] t-butylbicyclophosphorothionate (TBPS) autoradiography, membrane binding with [(3)H]flunitrazepam and [(3)H]muscimol, and comparison of miniature inhibitory postsynaptic current (mIPSC) parameters did not reveal any differences between homozygous gamma2I77/I77 and gamma2F77/F77 mice. However, quantitative immunoblot analysis of gamma2I77/I77 hippocampi showed some increased levels of gamma2, alpha1, alpha4 and delta subunits, suggesting that differences between strains may exist in unassembled subunit levels, but not in assembled receptors. Zolpidem (1 microm) enhanced the decay of mIPSCs in CA1 pyramidal cells of control (C57BL/6J, gamma2F77/F77) mice by approximately 60%, and peak amplitude by approximately 20% at 33-34 degrees C in vitro. The actions of zolpidem (100 nm or 1 microm) were substantially reduced in gamma2I77/I77 mice, although residual effects included a 9% increase in decay and 5% decrease in peak amplitude. Similar results were observed in CA1 stratum oriens/alveus interneurons. At network level, the effect of zolpidem (10 microm) on carbachol-induced oscillations in the CA3 area of gamma2I77/I77 mice was significantly different compared with controls. Thus, the gamma2F77I point mutation virtually abolished the actions of zolpidem on GABA(A) receptors in the hippocampus. However, some residual effects of zolpidem may involve receptors that do not contain the gamma2 subunit.

Sociodemographic and premedical school factors related to postgraduate physicians' humanistic performance.

In an extensive survey of postgraduate physicians in two teaching hospitals (N = 141) for their humanistic attitudes, values and behavior, all ratings of physicians' humanistic performance, including physicians' own scores on self-report measures, supervising faculty, nurses and patient ratings, were modestly but significantly correlated with each other. Sex, ethnic or racial background, year of training, marital status, number of children, Alpha-Omega-Alpha membership or number of articles published were unrelated to physicians' humanistic behavior. Several measures of humanism were positively correlated with having taken more courses in the social sciences and humanities, having had more early person-centered work experience and reporting that before medical school others had confided in them or sought their advice more frequently.

Affect and neutrality in physician behavior: a study of patients' values and satisfaction.

Physicians' emotional expressivity was contrasted with emotional neutrality in a study of consumers' preferences regarding physician behavior in the medical encounter. Two hundred twenty-seven health-science students completed instruments designed to measure the values they held regarding physicians' emotional expressions as well as their perceptions of and satisfaction with the emotional behavior of a physician presented in a videotape simulation. Overall, consumers attached a low value to neutrality and preferred affective behavior to it, although their previously held values did significantly influence their degree of satisfaction with neutral behavior by the physician. Values did not influence recognition of or satisfaction with the nonneutral emotions. This research also shed light on consumer reactions to other emotions including reassurance and humor.

Consumer values and subsequent satisfaction ratings of physician behavior.

The role of respondents' values in their evaluation of and satisfaction with medical care was explored in four health education settings. Two hundred and twenty-seven nursing, medical, and health psychology students completed a forced-choice instrument designed to measure their value preferences for technical quality of care, psychosocial concern, courtesy, and mutual participation style of interacting in a medical visit. They subsequently watched a standardized 14-minute videotape of a simulated physician-patient interaction and evaluated the physician's behavior from the patient point of view on the four dimensions using two popular methods for assessing patient satisfaction. Respondents' ratings of the medical encounter were more often significantly influenced by their values when the more subjective satisfaction measure was considered. In addition, respondents who valued technical quality more highly were more satisfied with the other three dimensions of physician behavior, while respondents who more highly valued psychosocial concerns were less satisfied with these three dimensions. Ratings of satisfaction with technical quality were not affected by respondents' values. The importance of these findings in assessing patient satisfaction is discussed.

Factors associated with life satisfaction among practicing internists.

The present study explored the relationship between satisfaction with life in general among 211 practicing internists and characteristics of their work, health, and life styles. Using a forced stepwise multiple regression analysis, 67% of the total variance in life satisfaction was accounted for by study variables. More satisfied physicians were more likely to be older, married, engaged in sexual intercourse more often, argued with or emotionally withdrew from family or friends less often, had fewer health problems, were less anxious and depressed, and experienced less job stress and more job satisfaction. Characteristics of the work setting, type of work activity (teaching, research, or patient care), number of patients seen, or hours worked per week were unrelated to satisfaction with life. The findings point to the importance of studying family life, mental health, and social relations in addition to work-related variables in order to understand and assess the quality of life among physicians.

Internal medicine patients' expectations for care during office visits.

OBJECTIVE: To describe internal medicine patients' expectations for care during office visits and to examine the relationship between fulfillment of expectations for care and visit satisfaction. DESIGN: Survey of patients and their physicians. SETTING: The internal medicine practice of faculty and housestaff at a large academic center in Southern California. PATIENTS: 396 patients aged 18 to 65 years were approached in the clinic waiting room prior to their scheduled visits; 337 (85%) agreed to participate and 304 (77%) turned in completed questionnaires. Postvisit physician surveys were received in 88% of the cases. MAIN MEASUREMENTS: The patients' previsit reports of the elements of care they thought necessary for their physicians to provide; the patients' and physicians' postvisit reports of the elements of care actually provided; and the patients' satisfaction with care. RESULTS: Among 28 specific elements of care, seven were considered necessary by a majority of the patients (examination of the eyes/ears/nose/throat, lungs, heart, and abdomen; blood testing; prognostic counseling; and discussion of patients' own ideas about management). A higher number of elements of care were thought necessary by patients who were nonwhite and had not completed college. Up to 38% of the patients reported not receiving elements of care they had considered necessary; specific agreement between physicians and patients about care not received ranged from 63% to 100%. Not receiving certain "necessary" elements of care was associated with lower visit satisfaction. CONCLUSION: Internal medicine patients at the center studied had specific expectations for the content of their physician visits. However, they routinely failed to receive some of the items they thought necessary. Unless patients' expectations are carefully elicited and dealt with the physician-patient relationship may be adversely affected.

Expert ratings of primary care goals and objectives.

OBJECTIVE: To develop consensus on proficiencies internal medicine residents should master in the area of primary and managed care. DESIGN: A draft compendium of primary care educational objectives including important clinical topics was developed at the Sepulveda Veterans Health Administration Medical Center Pilot Ambulatory Care and Education (PACE) Program as part of a local and regional primary care curricular review. Fifty-one experts, including leaders in the Society of General Internal Medicine, the Association of Program Directors in Internal Medicine, the American College of Physicians, general internal medicine division chiefs, and Veterans Affairs (VA) associate chiefs of staff for ambulatory care rated the compendium. MEASUREMENTS AND MAIN RESULTS: Eleven objectives and nine clinical topics were rated "critically important" (4.7 or above on a five-point scale). General internal medicine chiefs and associate chiefs of staff for ambulatory care judged them to be covered adequately in fewer than half of the 17 VA Western Region-affiliated internal medicine programs. Forty-five objectives and 77 clinical topics were considered at least somewhat important to the education of general internal medicine residents in primary care. The VA raters reported that in the prior academic year, their housestaffs had spent between 21% (postgraduate year I) and 33% (postgraduate year III) of their time in ambulatory care settings. CONCLUSION: With the emphasis on primary and managed care, there is a need for national consensus on educational objectives in primary care general internal medicine. This review provides educators with a benchmark to test the adequacy of their institutions' curricula in primary care internal medicine.

Modification of residents' behavior by preceptor feedback of patient satisfaction.

The authors tested the effect of preceptor feedback to residents of patients' ratings of perceived art and technical quality of care on residents' subsequent performances. New ambulatory patients were asked to complete questionnaires measuring satisfaction with physician behavior during initial encounters. Sixty-eight residents were evaluated by 424 patients over a six-month period. Continuing residents with the lowest scores were assigned to a feedback or a non-feedback group. Residents in the feedback group were individually shown their mean scores on each item, as well as scores for all residents, and were then advised of physicians' behaviors that could increase patient satisfaction. During a subsequent six-month survey of new patients, scores in the feedback group improved more than those in the non-feedback group in art of care, technical quality, and total patient satisfaction (p less than 0.001).

Measuring physicians' humanistic attitudes, values, and behaviors.

This paper describes the reliability and validity of 10 easily administered and scored self-report measures of physicians' humanistic attitudes, values, and behaviors. This research also provides evidence that evaluations of physicians' humanistic behavior made by their outpatients, and non-physician staff with whom they worked, and the faculty physicians supervising them on inpatient ward rotations were positively and significantly correlated with one another. The potential usefulness of a multi-modal approach in evaluating humanistic physician attributes in which self-report measures are combined with direct feedback from all of those who interact with physicians is discussed.

All thalamocortical neurones possess a T-type Ca2+ 'window' current that enables the expression of bistability-mediated activities.

1. The existence of a non-negligible steady-state ('window') component of the low threshold, T-type Ca2+current (IT) and an appropriately large ratio of IT to ILeak conductance (i.e. gT/gLeak) have been shown to underlie a novel form of intrinsic bistability that is present in about 15 % of thalamocortical (TC) neurones. 2. In the present experiments, the dynamic clamp technique was used to introduce into mammalian TC neurones in vitro either an artificial, i.e. computer-generated, IT in order to enhance endogenous IT, or an artificial inward ILeak to decrease endogenous ILeak. Using this method, we were able to investigate directly whether the majority of TC neurones appear non-bistable because their intrinsic ionic membrane properties are essentially different (i.e. presence of a negligible IT 'window' component), or simply because they possess a gT or gLeak conductance that is insufficiently large or small, respectively. 3. The validity of the dynamic clamp arrangement and the accuracy of artificial IT were confirmed by (i) recreating the low threshold calcium potential (LTCP) with artificial IT following its block by Ni2+ (0.5-1 mM), and (ii) blocking endogenous LTCPs with an artificial outward IT. 4. Augmentation of endogenous IT by an artificial analog or introduction of an artificial inward ILeak transformed all non-bistable TC neurones to bistable cells that expressed the full array of bistability-mediated behaviours, i.e. input signal amplification, slow oscillatory activity and membrane potential bistability. 5. These results demonstrate the existence of a non-negligible IT 'window' component in all TC neurones and suggest that rather than being a novel group of neurones, bistable cells are merely representative of an interesting region of dynamical modes in the (gT, gLeak) parameter space that may be expressed under certain physiological or pathological conditions by all TC neurones and other types of excitable cells that possess an IT 'window' component with similar biophysical properties.

Improving patient quality of life with feedback to physicians about functional status.

OBJECTIVE: To improve functional status among primary care patients. INTERVENTION: 1) Computer-generated feedback to physicians about the patient's functional status, the patient's self-reported "chief complaint," and problem-specific resource and management suggestions; and 2) two brief interactive educational sessions for physicians. DESIGN: Randomized controlled trial. SETTING: University primary care clinic. PARTICIPANTS: All 73 internal medicine house officers and 557 of their new primary care patients. MEASURES: 1) Change in patient functional status from enrollment until six months later, using the Functional Status Questionnaire (FSQ); 2) management plans and additional information about functional status abstracted from the medical record; and 3) physician attitude about whether internists should address functional status problems. RESULTS: Emotional well-being scores improved significantly for the patients of the experimental group physicians compared with those of the control group physicians (p < 0.03). Limitations in social activities indicated as "due to health" decreased among the elderly (> or = 70 years of age) individuals in the experimental group compared with the control group (p < 0.03). The experimental group physicians diagnosed more symptoms of stress or anxiety than did the control group physicians (p < 0.001) and took more actions recommended by the feedback form (p < 0.02). CONCLUSIONS: Computer-generated feedback of functional status screening results accompanied by resource and management suggestions can increase physician diagnoses of impaired emotional well-being, can influence physician management of functional status problems, and can assist physicians in improving emotional well-being and social functioning among their patients.