Effects of a Multiple Schedule of Collective Reinforcement on Shaping the Cultivative Response Rate of Three-man Teams

The principle of reinforcement developed by experimenting with individual subjects has been extended in recent years for use with groups. In most of these studies some social interaction within the group is reinforced. For example, Azrin and Lindsley (1956) and Lindsley (1961) have manipulated imitation, cooperation, and competition between two subjects in an operant conditioning situation. Levin and Shapiro (1962) manipulated conversation between members of a group through appropriate reinforcement. Glaser and Klaus (1962) conditioned a team of two monitors and an observer to respond as a unit by reinforcing the group only when each member had made the proper response

Communication calls produced by electrical stimulation of four structures in the guinea pig brain

One of the main central processes affecting the cortical representation of conspecific vocalizations is the collateral output from the extended motor system for call generation. Before starting to study this interaction we sought to compare the characteristics of calls produced by stimulating four different parts of the brain in guinea pigs (Cavia porcellus). By using anaesthetised animals we were able to reposition electrodes without distressing the animals. Trains of 100 electrical pulses were used to stimulate the midbrain periaqueductal grey (PAG), hypothalamus, amygdala, and anterior cingulate cortex (ACC). Each structure produced a similar range of calls, but in significantly different proportions. Two of the spontaneous calls (chirrup and purr) were never produced by electrical stimulation and although we identified versions of chutter, durr and tooth chatter, they differed significantly from our natural call templates. However, we were routinely able to elicit seven other identifiable calls. All seven calls were produced both during the 1.6 s period of stimulation and subsequently in a period which could last for more than a minute. A single stimulation site could produce four or five different calls, but the amygdala was much less likely to produce a scream, whistle or rising whistle than any of the other structures. These three high-frequency calls were more likely to be produced by females than males. There were also differences in the timing of the call production with the amygdala primarily producing calls during the electrical stimulation and the hypothalamus mainly producing calls after the electrical stimulation. For all four structures a significantly higher stimulation current was required in males than females. We conclude that all four structures can be stimulated to produce fictive vocalizations that should be useful in studying the relationship between the vocal motor system and cortical sensory representation

Evaluation of an MRI-based protocol for cell implantation in four patients with Huntington's disease

The purpose of this study was to evaluate our surgical protocol for the preparation and delivery of suspensions of fetal tissue into the diseased human brain. We implanted suspensions of human fetal striatal anlage into the right caudate and putamen of four patients with Huntington's disease. Postoperative 3 tesla MR imaging confirmed accurate graft placement. Variability in graft survival was noted and the MR signal changes over 6 months revealed persistent hyperintense signal on T2-weighted images. Our results are consistent with those described by other groups and indicate that our surgical protocol is safe, accurate, and reproducible

Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries

<div><p>We recently identified sphingosine-1-phosphate (S1P) signaling and the cystic fibrosis transmembrane conductance regulator (CFTR) as prominent regulators of myogenic responsiveness in rodent resistance arteries. However, since rodent models frequently exhibit limitations with respect to human applicability, translation is necessary to validate the relevance of this signaling network for clinical application. We therefore investigated the significance of these regulatory elements in human mesenteric and skeletal muscle resistance arteries. Mesenteric and skeletal muscle resistance arteries were isolated from patient tissue specimens collected during colonic or cardiac bypass surgery. Pressure myography assessments confirmed endothelial integrity, as well as stable phenylephrine and myogenic responses. Both human mesenteric and skeletal muscle resistance arteries (i) express critical S1P signaling elements, (ii) constrict in response to S1P and (iii) lose myogenic responsiveness following S1P receptor antagonism (JTE013). However, while human mesenteric arteries express CFTR, human skeletal muscle resistance arteries do not express detectable levels of CFTR protein. Consequently, modulating CFTR activity enhances myogenic responsiveness only in human mesenteric resistance arteries. We conclude that human mesenteric and skeletal muscle resistance arteries are a reliable and consistent model for translational studies. We demonstrate that the core elements of an S1P-dependent signaling network translate to human mesenteric resistance arteries. Clear species and vascular bed variations are evident, reinforcing the critical need for further translational study.</p></div

S1P signaling in human skeletal muscle resistance arteries.

<p>(A) Human skeletal muscle resistance arteries express mRNA encoding critical sphingosine-1-phosphate (S1P) signaling elements (N = 8 patient samples), including sphingosine kinase 1 (Sphk1), S1P phosphohydrolase 1 (SPP1) and S1P receptor subtypes 1–3 (S1P₁R, S1P₂R and S1P₃R). In terms of relative expression, S1P₁R is the most highly expressed; S1P₃R is more highly expressed than S1P₂R (N = 8). Human skeletal muscle resistance arteries (B) express detectable levels of cystic fibrosis transmembrane conductance regulator (CFTR) mRNA (N = 8); however, (C) CFTR protein is not detected (N = 5). In (C), tubulin confirms adequate loading. (D) S1P stimulates dose-dependent vasoconstriction (dia_max = 122.2±16.5μm; n = 6 vessels from N = 4 patients). (E) S1P receptor antagonism (100pmol/L JTE013: dia_max = 132±15μm, n = 8, N = 5) attenuates myogenic tone. However, neither (F) sub-threshold concentrations of S1P (10nmol/L S1P: dia_max = 110±20μm; n = 5, N = 4) nor (G) CFTR inhibition (10pmol/L CFTR_(inh)-172: dia_max = 139±33μm, n = 5, N = 4) modulate myogenic tone. Dia_max is defined as the maximal diameter (under calcium free buffer conditions) at 60mmHg. In Panel A, * denotes P<0.05 relative to all other receptor subtypes (Friedman ANOVA). Panels E, F and G were statistically compared with a paired two-way ANOVA; in Panel E, * denotes P<0.05 relative to the pre-treatment control response.</p

Human mesenteric and skeletal muscle resistance artery vasodilator responses.

<p>Human (A) mesenteric (n = 7 vessels from N = 3 patients) and (B) skeletal muscle (n = 8, N = 5) resistance arteries constrict in response to 10^-5 mol/L phenylephrine (open circles) and dose-dependently dilate when acetylcholine is subsequently co-applied (closed circles). For mesenteric arteries: dia_max = 255±23μm and logEC₅₀ = -7.4±0.2. For skeletal muscle arteries: dia_max = 133±22μm and logEC₅₀ = -7.2±0.2. Dia_max is defined as the maximal diameter (under calcium free buffer conditions) at 60mmHg.</p

Response stability in human mesenteric and skeletal muscle resistance arteries.

<p>Time-control experiments confirm that (A) phenylephrine (PE)-stimulated vasoconstriction (logEC₅₀ = -6.4±0.2; dia_max = 173±33μm; n = 7 vessels from N = 5 patients), (B) myogenic tone (dia_max = 185±34μm; n = 7, N = 4) and (C) active myogenic constriction (following a pressure step from 60mmHg to 100mmHg; dia_max = 105±15μm; n = 7, N = 3) are consistent in human mesenteric resistance arteries over two separate assessments. (D) PE-stimulated vasoconstriction (logEC₅₀ = -6.5±0.1; dia_max = 104±13μm; n = 10, N = 10) and (E) myogenic tone (dia_max = 122±21μm; n = 9, N = 8) are also consistent over two separate assessments in human skeletal muscle resistance arteries; however, (F) active myogenic constriction (dia_max = 94±9μm; n = 7, N = 6) is not stable. Dia_max is defined as the maximal diameter (under calcium free buffer conditions) at 60mmHg. Myogenic tone (Panels A and D) and PE responses (Panels B and E) were statistically compared with a paired two-way ANOVA; active constriction measures (Panels C and F) were compared with a Wilcoxon test. * denotes P<0.05 for a paired comparisons.</p