Centre and surround responses of marmoset lateral geniculate neurones at different temporal frequencies

The responses of marmoset lateral geniculate neurones to stimuli that were composed of a sinusoidally modulating centre stimulus and a surround that was modulated in counterphase were measured. The size of the stimulus centre was varied. These measurements were repeated at different temporal frequencies between 1 and 30 Hz. The response amplitudes and phases depended in a characteristic manner on the stimulus centre size. The response behaviour could be modelled by assuming Gaussian responsivity profiles of the cells' receptive field (RF) centres and surrounds and a phase delay in the RF surround responses, relative to the centre, enabling the description of RF centre and surround response characteristics. We found that the RF centre-to-surround phase difference increased linearly with increasing temporal frequency, indicating a constant delay difference of about 4.5 to 6 ms. A linear model, including low-pass filters, a lead lag stage and a delay, was used to describe the mean RF centre and surround responses. The separate RF centre and surround responses were less band pass than the full receptive field responses of the cells. The linear model provided less satisfactory fits to M-cell responses than to those of P-cells, indicating additional nonlinearities

Adaptive Responses Account for the β-Curve—Hormesis is Linked to Acquired Tolerance

To date there is no single shared property of the various physical and chemical agents that elicit the β-curve to account for its form, leading to the proposition that hormesis is a consequence of the nonspecificity of adaptive responses. It is argued that adaptive responses to toxic agents may be expected to follow the β-curve. Four kinds of examples are reviewed (enzyme activity, sequestration and repair, and reproductive and homeostatic responses) that corroborate this proposition. The homeostasis example (incorporating homeorhesis) is considered in more detail, using the author’s published hydroid experimental growth data, to show that both the α- and β-curves are satisfactorily explained in this way. Many consider that hormesis is merely due to regulatory overcorrections, but it is proposed that it is a consequence of adaptations of the rate-sensitive growth control mechanism (homeorhesis) to sustained levels of inhibition to which the growth control mechanism adapts. In response to low levels of inhibition, upward adjustment of preferred growth rates confers greater resistance to inhibition, with growth hormesis as a cumulative byproduct

A reappraisal of the blood glucose homeostat which comprehensively explains the type 2 diabetes mellitus–syndrome X complex

Blood glucose concentrations are unaffected by exercise despite very high rates of glucose flux. The plasma ionised calcium levels are even more tightly controlled after meals and during lactation. This implies ‘integral control’. However, pairs of integral counterregulatory controllers (e.g. insulin and glucagon, or calcitonin and parathyroid hormone) cannot operate on the same controlled variable, unless there is some form of mutual inhibition. Flip-flop functional coupling between pancreatic α- and β-cells via gap junctions may provide such a mechanism. Secretion of a common inhibitory chromogranin by the parathyroids and the thyroidal C-cells provides another. Here we describe how the insulin:glucagon flip-flop controller can be complemented by growth hormone, despite both being integral controllers. Homeostatic conflict is prevented by somatostatin-28 secretion from both the hypothalamus and the pancreatic islets. Our synthesis of the information pertaining to the glucose homeostat that has accumulated in the literature predicts that disruption of the flip-flop mechanism by the accumulation of amyloid in the pancreatic islets in type 2 diabetes mellitus will lead to hyperglucagonaemia, hyperinsulinaemia, insulin resistance, glucose intolerance and impaired insulin responsiveness to elevated blood glucose levels. It explains syndrome X (or metabolic syndrome) as incipient type 2 diabetes in which the glucose control system, while impaired, can still maintain blood glucose at the desired level. It also explains why it is characterised by high plasma insulin levels and low plasma growth hormone levels, despite normoglycaemia, and how this leads to central obesity, dyslipidaemia and cardiovascular disease in both syndrome X and type 2 diabetes