On the neural correlates of visual perception.
Neurological findings suggest that the human striate cortex (V1) is an indispensable component of a neural substratum subserving static achromatic form perception in its own right and not simply as a central distributor of retinally derived information to extrastriate visual areas. This view is further supported by physiological evidence in primates that the finest-grained conjoined representation of spatial detail and retinotopic localization that underlies phenomenal visual experience for local brightness discriminations is selectively represented at cortical levels by the activity of certain neurons in V1. However, at first glance, support for these ideas would appear to be undermined by incontrovertible neurological evidence (visual hemineglect and the simultanagnosias) and recent psychophysical results on 'crowding' that confirm that activation of neurons in V1 may, at times, be insufficient to generate a percept. Moreover, a recent proposal suggests that neural correlates of visual awareness must project directly to those in executive space, thus automatically excluding V1 from a related perceptual space because V1 lacks such direct projections. Both sets of concerns are, however, resolved within the context of adaptive resonance theories. Recursive loops, linking the dorsal lateral geniculate nucleus (LGN) through successive cortical visual areas to the temporal lobe by means of a series of ascending and descending pathways, provide a neuronal substratum at each level within a modular framework for mutually consistent descriptions of sensory data. At steady state, such networks obviate the necessity that neural correlates of visual experience project directly to those in executive space because a neural phenomenal perceptual space subserving form vision is continuously updated by information from an object recognition space equivalent to that destined to reach executive space. Within this framework, activity in V1 may engender percepts that accompany figure-ground segregations only when dynamic incongruities are resolved both within and between ascending and descending streams. Synchronous neuronal activity on a short timescale within and across cortical areas, proposed and sometimes observed as perceptual correlates, may also serve as a marker that a steady state has been achieved, which, in turn, may be a requirement for the longer time constants that accompany the emergence and stability of perceptual states compared to the faster dynamics of adapting networks and the still faster dynamics of individual action potentials. Finally, the same consensus of neuronal activity across ascending and descending pathways linking multiple cortical areas that in anatomic sequence subserve phenomenal visual experiences and object recognition may underlie the normal unity of conscious experience. (+info
Trans-synaptically induced bursts in regular spiking non-pyramidal cells in deep layers of the cat motor cortex.
In deep layers of the cat motor cortex, we have investigated the properties of neurons displaying trans-synaptically induced bursts. In in vivo experiments, extracellularly recorded burst neurons were separated into two subtypes based on their dependence on stimulation sites, the medullary pyramid or the ventrolateral (VL) thalamic nucleus, from which bursts of 10-20 spikes were triggered. The spike amplitude attenuation and frequency adaptation during a burst were more prominent in pyramid-dependent burst neurons than in VL-dependent burst neurons. Intracellular recordings in in vivo experiments revealed that pyramid-dependent bursts emerged from a long-lasting depolarization, while each spike during a VL-dependent burst was narrow in half-width and was followed by a fast AHP, similar to fast spiking neurons. In in vitro slice experiments, intracellular recordings were obtained from neurons that displayed a burst of attenuated spikes emerging from a long-lasting depolarization, and were also obtained from fast spiking neurons. They were morphologically recovered to be multipolar cells with sparsely spiny dendrites and local axonal networks, suggesting that they are inhibitory interneurons. The multipolar neurons displaying bursts of attenuated spikes may mediate the recurrent inhibition of pyramidal tract cells. (+info
Lysine deficiency alters diet selection without depressing food intake in rats.
Under states of protein deficiency, the dietary limiting amino acid, rather than protein content, can act as the dietary stimulus to control diet selection. If fact, threonine-deficient rats will alter their diet selection patterns solely on the basis of very small changes (0.009 g/100 g) in the dietary threonine concentration. In these studies, we assessed whether lysine-deficient rats will also alter their diet selection patterns on the basis of small changes in dietary Lys concentration. In all experiments, growing rats were adapted to diets in which the protein fraction (purified amino acids or wheat gluten) was limiting in Lys. They were then given a choice between the adaptation diet (AD) diet and a slightly more deficient diet. Rats that were adapted to a Lys-deficient diet (0.25 g Lys/100 g) selected their AD over diets containing as little as 0.01% less Lys (P < 0.01) within 5 d. To determine how deficient rats must be before they alter their selection patterns, rats were adapted to diets containing various levels of Lys, i.e., 2 levels below the requirement for growth and 2 levels above the requirement for growth, but below the requirement for maximal nitrogen retention. Only rats adapted to diets containing Lys below their requirement for growth selected their AD over a diet containing 0.05% less Lys (P < 0.005). Finally, to determine whether rats will alter their selection to whole protein-based diets, rats were adapted to 25% wheat gluten diets supplemented with 0.03-0.21% Lys. Rats selected the AD over a diet containing as little as 0.09% less supplemental Lys by d 4 of the trial (P < 0.05). We conclude that rats are sensitive to changes as small as 0.01% in dietary Lys concentration, but that sensitivity requires prior adaptation to Lys-deficient diets. (+info
Changes in protein tyrosine phosphorylation in the rat brain after cerebral ischemia in a model of ischemic tolerance.
A brief period of sublethal cerebral ischemia, followed by several days of recovery, renders the brain resistant to a subsequent lethal ischemic insult, a phenomenon termed ischemic preconditioning or tolerance. Ischemic tolerance was established in the rat two-vessel occlusion model of ischemia, induced by occlusion of both carotid arteries in combination with hypotension. Ischemic preconditioning (3 minutes) provided maximal neuroprotection when induced 2 days prior to a lethal ischemic insult of 9-minute duration. Neuroprotection persisted for at least 8 weeks. Since neurotransmission has been implicated in ischemic cell death, the effect of ischemic preconditioning on tyrosine phosphorylation of proteins and on the levels of glutamate receptor subunits in hippocampus and neocortex was studied. Regional levels of tyrosine phosphorylation of proteins in general and the N-methyl-D-aspartate receptor subunit NR2 in particular are markedly enhanced after ischemia in nonconditioned brains, in both the synaptosomal fraction and the whole-tissue homogenate of rat neocortex and hippocampus, but recover to control levels only in the preconditioned brain. Ischemic preconditioning selectively induces a decrease in the levels of the NR2A and NR2B subunits and a modest decrease in the levels of NR1 subunit proteins in the synaptosomal fraction of the neocortex but not hippocampus after the second lethal ischemia. It was concluded that ischemic preconditioning prevents a persistent change in cell signaling as evidenced by the tyrosine phosphorylation of proteins after the second lethal ischemic insult, which may abrogate the activation of detrimental cellular processes leading to cell death. (+info
Fibrocartilage in tendons and ligaments--an adaptation to compressive load.
Where tendons and ligaments are subject to compression, they are frequently fibrocartilaginous. This occurs at 2 principal sites: where tendons (and sometimes ligaments) wrap around bony or fibrous pulleys, and in the region where they attach to bone, i.e. at their entheses. Wrap-around tendons are most characteristic of the limbs and are commonly wider at their point of bony contact so that the pressure is reduced. The most fibrocartilaginous tendons are heavily loaded and permanently bent around their pulleys. There is often pronounced interweaving of collagen fibres that prevents the tendons from splaying apart under compression. The fibrocartilage can be located within fascicles, or in endo- or epitenon (where it may protect blood vessels from compression or allow fascicles to slide). Fibrocartilage cells are commonly packed with intermediate filaments which could be involved in transducing mechanical load. The ECM often contains aggrecan which allows the tendon to imbibe water and withstand compression. Type II collagen may also be present, particularly in tendons that are heavily loaded. Fibrocartilage is a dynamic tissue that disappears when the tendons are rerouted surgically and can be maintained in vitro when discs of tendon are compressed. Finite element analyses provide a good correlation between its distribution and levels of compressive stress, but at some locations fibrocartilage is a sign of pathology. Enthesis fibrocartilage is most typical of tendons or ligaments that attach to the epiphyses of long bones where it may also be accompanied by sesamoid and periosteal fibrocartilages. It is characteristic of sites where the angle of attachment changes throughout the range of joint movement and it reduces wear and tear by dissipating stress concentration at the bony interface. There is a good correlation between the distribution of fibrocartilage within an enthesis and the levels of compressive stress. The complex interlocking between calcified fibrocartilage and bone contributes to the mechanical strength of the enthesis and cartilage-like molecules (e.g. aggrecan and type II collagen) in the ECM contribute to its ability to withstand compression. Pathological changes are common and are known as enthesopathies. (+info
Small conductance potassium channels cause an activity-dependent spike frequency adaptation and make the transfer function of neurons logarithmic.
We made a computational model of a single neuron to study the effect of the small conductance (SK) Ca2+-dependent K+ channel on spike frequency adaptation. The model neuron comprised a Na+ conductance, a Ca2+ conductance, and two Ca2+-independent K+ conductances, as well as a small and a large (BK) Ca2+-activated K+ conductance, a Ca2+ pump, and mechanisms for Ca2+ buffering and diffusion. Sustained current injection that simulated synaptic input resulted in a train of action potentials (APs) which in the absence of the SK conductance showed very little adaptation with time. The transfer function of the neuron was nearly linear, i.e., both asymptotic spike rate as well as the intracellular free Ca2+ concentration ([Ca2+]i) were approximately linear functions of the input current. Adding an SK conductance with a steep nonlinear dependence on [Ca2+]i (. Pflugers Arch. 422:223-232; Kohler, Hirschberg, Bond, Kinzie, Marrion, Maylie, and Adelman. 1996. Science. 273:1709-1714) caused a marked time-dependent spike frequency adaptation and changed the transfer function of the neuron from linear to logarithmic. Moreover, the input range the neuron responded to with regular spiking increased by a factor of 2.2. These results can be explained by a shunt of the cell resistance caused by the activation of the SK conductance. It might turn out that the logarithmic relationships between the stimuli of some modalities (e.g., sound or light) and the perception of the stimulus intensity (Fechner's law) have a cellular basis in the involvement of SK conductances in the processing of these stimuli. (+info
Chemotactic responses of Escherichia coli to small jumps of photoreleased L-aspartate.
Computer-assisted motion analysis coupled to flash photolysis of caged chemoeffectors provides a means for time-resolved analysis of bacterial chemotaxis. Escherichia coli taxis toward the amino acid attractant L-aspartate is mediated by the Tar receptor. The physiology of this response, as well as Tar structure and biochemistry, has been studied extensively. The beta-2, 6-dinitrobenzyl ester of L-aspartic acid and the 1-(2-nitrophenyl)ethyl ether of 8-hydroxypyrene-1,3,6-tris-sulfonic acid were synthesized. These compounds liberated L-aspartate and the fluorophore 8-hydroxypyrene 1,3,6-tris-sulfonic acid (pyranine) upon irradiation with near-UV light. Photorelease of the fluorophore was used to define the amplitude and temporal stability of the aspartate jumps employed in chemotaxis experiments. The dependence of chemotactic adaptation times on aspartate concentration, determined in mixing experiments, was best fit by two Tar aspartate-binding sites. Signal processing (excitation) times, amplitudes, and adaptive recovery of responses elicited by aspartate jumps producing less than 20% change in receptor occupancy were characterized in photorelease assays. Aspartate concentration jumps in the nanomolar range elicited measurable responses. The response threshold and sensitivity of swimming bacteria matched those of bacteria tethered to glass by a single flagellum. Stimuli of similar magnitude, delivered either by rapid mixing or photorelease, evoked responses of similar strength, as assessed by recovery time measurements. These times remained proportional to change in receptor occupancy close to threshold, irrespective of prior occupancy. Motor excitation responses decayed exponentially with time. Rates of excitation responses near threshold ranged from 2 to 7 s-1. These values are consistent with control of excitation signaling by decay of phosphorylated pools of the response regulator protein, CheY. Excitation response rates increased slightly with stimulus size up to values limited by the instrumentation; the most rapid was measured to be 16 +/- 3 (SE) s-1. This increase may reflect simultaneous activation of CheY dephosphorylation, together with inhibition of its phosphorylation. (+info
Impact of vascular adaptation to chronic aortic regurgitation on left ventricular performance.
BACKGROUND: This investigation was designed to test the hypothesis that vascular adaptation occurs in patients with chronic aortic regurgitation to maintain left ventricular (LV) performance. METHODS AND RESULTS: Forty-five patients with chronic aortic regurgitation (mean age 50+/-14 years) were studied using a micromanometer LV catheter to obtain LV pressures and radionuclide ventriculography to obtain LV volumes during multiple loading conditions and right atrial pacing. These 45 patients were subgrouped according to their LV contractility (Ees) and ejection fraction values. Group I consisted of 24 patients with a normal Ees. Group IIa consisted of 10 patients with impaired Ees values (Ees <1.00 mm Hg/mL) but normal LV ejection fractions; Group IIb consisted of 11 patients with impaired contractility and reduced LV ejection fractions. The left ventricular-arterial coupling ratio, Ees/Ea, where Ea was calculated by dividing the LV end-systolic pressure by LV stroke volume, averaged 1.60+/-0.91 in Group I. It decreased to 0.91+/-0.27 in Group IIa (P<0.05 versus Group I), and it decreased further in Group IIb to 0.43+/-0.24 (P<0.001 versus Groups I and IIa). The LV ejection fractions were inversely related to the Ea values in both the normal and impaired contractility groups (r=-0.48, P<0.05 and r=-0.56, P<0.01, respectively), although the slopes of these relationships differed (P<0.05). The average LV work was maximal in Group IIa when the left ventricular-arterial coupling ratio was near 1.0 because of a significant decrease in total arterial elastance (P<0.01 versus Group I). In contrast, the decrease in the left ventricular-arterial coupling ratio in Group IIb was caused by an increase in total arterial elastance, effectively double loading the LV, contributing to a decrease in LV pump efficiency (P<0.01 versus Group IIa and P<0.001 versus Group I). CONCLUSIONS: Vascular adaptation may be heterogeneous in patients with chronic aortic regurgitation. In some, total arterial elastance decreases to maximize LV work and maintain LV performance, whereas in others, it increases, thereby double loading the LV, contributing to afterload excess and a deterioration in LV performance that is most prominent in those with impaired contractility. (+info