Spiral mechanisms are required to account for summation of complex motion components

Stimuli from one family of complex motions are defined by their spiral pitch, where cardinal axes represent signed expansion and rotation. Intermediate spirals are represented by intermediate pitches. It is well established that vision contains mechanisms that sum over space and direction to detect these stimuli (Morrone et al., Nature 376 (1995) 507) and one possibility is that four cardinal mechanisms encode the entire family. We extended earlier work (Meese & Harris, Vision Research 41 (2001) 1901) using subthreshold summation of random dot kinematograms and a two-interval forced choice technique to investigate this possibility. In our main experiments, the spiral pitch of one component was fixed and that of another was varied in steps of 15° relative to the first. Regardless of whether the fixed component was aligned with cardinal axes or an intermediate spiral, summation to-coherence-threshold between the two components declined as a function of their difference in spiral pitch. Similar experiments showed that none of the following were critical design features or stimulus parameters for our results: superposition of signal dots, limited life-time dots, the presence of speed gradients, stimulus size or the number of dots. A simplex algorithm was used to fit models containing mechanisms spaced at a pitch of either 90° (cardinal model) or 45° (cardinal+model) and combined using a fourth-root summation rule. For both models, direction half-bandwidth was equated for all mechanisms and was the only free parameter. Only the cardinal+model could account for the full set of results. We conclude that the detection of complex motion in human vision requires both cardinal and spiral mechanisms with a half-bandwidth of approximately 46°. © 2002 Elsevier Science Ltd. All rights reserved.

Orexin-stimulated MAP kinase cascades are activated through multiple G-protein signalling pathways in human H295R adrenocortical cells: diverse roles for orexins A and B

Orexins A and B (ORA and ORB) are neuropeptide hormones found throughout the central nervous system and periphery. They are required for a host of physiological processes including mitogen-activated protein kinase (MAPK) regulation, steroidogenesis, appetite control and energy regulation. While some signalling mechanisms have been proposed for individual recombinant orexin receptors in generic mammalian cell types, it is clear that the peripheral effects of orexin are spatially and temporally complex. This study dissects the different G-protein signalling and MAPK pathways activated in a pluripotent human adrenal H295R cell line capable of all the physiological steps involved in steroidogenesis. Both extracellular receptor kinase 1/2 (ERK1/2) and p38 were phosphorylated rapidly with a subsequent decline, in a time- and dose-dependent manner, in response to both ORA and ORB. Conversely, there was little or no direct activation of the ERK5 or JNK pathway. Analysis using signalling and MAPK inhibitors as well as receptor-specific antagonists determined the precise mediators of the orexin response in these cells. Both ERK1/2 and p38 activation were predominantly Gq- and to a lesser extent Gs-mediated; p38 activation even had a small Gi-component. Effects were broadly comparable for both orexin sub-types ORA and ORB and although most of the effects were transmitted through the orexin receptor-1 subtype, we did observe a role for orexin receptor-2-mediated activation of both ERK1/2 and p38. Cortisol secretion also differed in response to ORA and ORB. These data suggest multiple roles for orexin-mediated MAPK activation in an adrenal cell-line, this complexity may help to explain the diverse biological actions of orexins with wide-ranging consequences for our understanding of the mechanisms initiated by these steroidogenic molecules.

Limitations of the isolated GP-STN network

An in vitro mouse slice preparation from control and MPTP-treated mice in which functional reciprocal GP-STN connectivity is maintained, does not produce oscillatory bursting or synchronous activity neuronal activity. Pharmacological interventions that produce bursting activity do so without concomitant neuronal synchrony, or a requirement for glutamate or GABA transmission. Pre-treatment with MPTP did not alter this behaviour. Thus, we have no evidence that the functionally connected, but isolated, GP — STN network can act as a pacemaker for synchronous correlated activity in the basal ganglia and must conclude that other inputs such as those from cortex and/or striatum are required.