Dissociation of visual, motor and predictive signals in parietal cortex during visual guidance.

The role of the posterior parietal cortex (PPC) in the visual guidance of movements was studied in monkeys trained to use a joystick to guide a spot to a target. Visual and motor influences were dissociated by transiently occluding the spot and by varying the relationship between the direction of joystick and spot movements. We found a strong segregation of function in PPC during visual guidance. Neurons in area MST were selectively modulated by the direction of visible moving stimuli, whereas neurons in area MIP were selectively modulated by the direction of hand movement. In contrast, the selectivity of cells in the lateral intraparietal area (LIP) did not directly depend on either visual input or motor output, but rather seemed to encode a predictive representation of stimulus movement. These predictive signals may be an important link in visuomotor transformations.

Visual response latencies of magnocellular and parvocellular LGN neurons in macaque monkeys.

Signals relayed through the magnocellular layers of the LGN travel on axons with faster conduction speeds than those relayed through the parvocellular layers. As a result, magnocellular signals might reach cerebral cortex appreciably before parvocellular signals. The relative speed of these two channels cannot be accurately predicted based solely on axon conduction speeds, however. Other factors, such as different degrees of convergence in the magnocellular and parvocellular channels and the retinal circuits that feed them, can affect the time it takes for magnocellular and parvocellular signals to activate cortical neurons. We have investigated the relative timing of visual responses mediated by the magnocellular and parvocellular channels. We recorded individually from 78 magnocellular and 80 parvocellular neurons in the LGN of two anesthetized monkeys. Visual response latencies were measured for small spots of light of various intensities. Over a wide range of stimulus intensities the fastest magnocellular response latencies preceded the fastest parvocellular response latencies by about 10 ms. Because parvocellular neurons are far more numerous than magnocellular neurons, convergence in cortex could reduce the magnocellular advantage by allowing parvocellular signals to generate detectable responses sooner than expected based on the responses of individual parvocellular neurons. An analysis based on a simple model using neurophysiological data collected from the LGN shows that convergence in cortex could eliminate or reverse the magnocellular advantage. This observation calls into question inferences that have been made about ordinal relationships of neurons based on timing of responses.

Neuronal correlates of inferred motion in primate posterior parietal cortex.

For many types of behaviours, it is necessary to monitor the position or movement of objects that are temporarily occluded. The primate posterior parietal cortex contains neurons that are active during visual guidance tasks: in some cases, even if the visual target disappears transiently. It has been proposed that activity of this sort could be related to current or planned eye movements, but it might also provide a more generalized abstract representation of the spatial disposition of targets, even when they are not visible. We have recorded from monkey posterior parietal cortex while the animal viewed a visual stimulus that disappeared, and then, depending on experimental context, could be inferred to be either moving or stationary. During this temporary absence of the stimulus, about half of the neurons were found to be significantly more active on those trials in which the stimulus could be presumed to be moving rather than stationary. The activity was thus present in the absence of either sensory input or motor output, suggesting that it may indeed constitute a generalized representation of target motion.

An active motor model for adaptation by vertebrate hair cells.

Bullfrog saccular hair cells adapt to maintained displacements of their stereociliary bundles by shifting their sensitive range, suggesting an adjustment in the tension felt by the transduction channels. It has been suggested that steady-state tension is regulated by the balance of two calcium-sensitive processes: passive "slipping" and active "tensioning." Here we propose a mathematical model for an adaptation motor that regulates tension, and describe some quantitative tests of the model. Slipping and tensioning rates were determined at membrane potentials of -80 and +80 mV. With these, the model predicts that the I(X) curve (relating bundle displacement and channel open probability) should shift negatively by 124 nm when the cell is depolarized, with an exponential time course that is slower on depolarization from -80 to +80 mV than on repolarization. This was observed: on depolarization, the I(X) curve shifted by an average of 139 nm, and displayed the expected difference in rates at the two potentials. Because the negative shift of the I(X) curve on depolarization represents an increase in the tension on transduction channels, the model also predicts this tension should cause an unrestrained bundle to pivot negatively by 99 nm on depolarization. Such movement was observed using high-resolution video microscopy; its amplitude was variable but ranged up to about 100 nm, and its time course was asymmetric in the same way as that of the I(X) curve shift. In additional comparisons, the active bundle movements and I(X) curve shift exhibited a similar steady-state voltage dependence, and were both reversibly abolished by reduced bath Ca2+ or by the transduction channel blocker streptomycin. Lastly, among different cells, the amplitude of the movement increased with the size of the transduction current. Thus, a quantitative mechanical model for adaptation also accounts for the observed mechanical behavior of the bundle, suggesting that the same mechanism is responsible for both, and that adaptation is mediated by an active, force-producing mechanism.

Tip-link integrity and mechanical transduction in vertebrate hair cells.

An attractive hypothesis for hair-cell transduction is that fine, filamentous "tip links" pull directly on mechanically sensitive ion channels located at the tips of the stereocilia. We tested the involvement of tip links in the transduction process by treating bundles with a BAPTA-buffered, low-Ca2+ saline (10(-9) M). BAPTA abolished the transduction current in a few hundred milliseconds. BAPTA treatment for a few seconds eliminated the tip links observed by either scanning or transmission electron microscopy. BAPTA also eliminated the voltage-dependent movement and caused a positive bundle displacement of 133 nm, in quantitative agreement with a model for regulation of tension. We conclude that tip links convey tension to the transduction channels of hair cells.

Regulation of tension on hair-cell transduction channels: displacement and calcium dependence.

An epithelial preparation of the bullfrog sacculus was used to characterize the initial rate of the adaptation mechanism in hair cells and its dependence on displacement and calcium. The I(X) curve relating transduction current and bundle displacement shifted along the X-axis without substantial change in slope, as previously observed, suggesting that adaptation involves a change in the attachment point of the elastic element connected to ion channels. If the "tip links" model of transduction is correct, this implies that one end of the link moves along the side of the stereocilium. The rates were highly asymmetric: in the tensioning direction the rate was roughly constant at 1-2 microns/sec (calculated as motion along a stereocilium); this is similar to that of myosin on actin. In the relaxing direction it appeared linearly dependent on tension. Calcium preferentially potentiated the relaxation, and apparently reduced the resting tension in the elastic element. The calcium site appears specific for calcium, as other divalent cations inhibited its action. Dihydrostreptomycin inhibited the positive rate, but its effect could not be explained by a simple channel block, and it seems inconsistent with screening of negative charge in the mouth of the transduction channel.

Voltage dependence of adaptation and active bundle movement in bullfrog saccular hair cells.

Hair cells of the bullfrog sacculus adapt to maintained displacement stimuli in a manner that suggests an active regulation of the tension stimulus reaching transduction channels. We have examined adaptation in dissociated hair cells by whole-cell patch-clamp recording and video microscopy. Adaptation was present in these cells, and it depended on extracellular calcium. The adaptation rate--as well as the position of the resting current-displacement curve--also depended on membrane potential, suggesting that calcium passes into the cytoplasm to reach its site of action. After abrupt hyperpolarization, the adaptation rate increased within milliseconds, suggesting that the calcium site is within a few micrometers of the ion channels through which calcium enters. The voltage dependence of the resting current-displacement curve, together with the "gating springs" hypothesis for transduction, predicts movement of the bundle away from the kinocilium when the cell is depolarized. This was observed.

Urotensin II lowers cytoplasmic free calcium concentration in goby enterocytes: measurements using quin2.

A technique is described for the measurement of cytoplasmic free calcium concentration ([Ca2+]c) in a suspension of goby intestinal epithelial cells using the fluorescent probe quin2. For 18 cell suspensions, [Ca2+]c was determined to be 142 +/- 14 nM. The caudal neurosecretory peptide urotensin II at 10(-7) to 10(-6) M concentration reduced [Ca2+]c by 20-50%. Together with previous findings linking the calcium-calmodulin system with the stimulation of Na+ and Cl- absorption in this tissue, it appears that alterations in cytoplasmic Ca2+ may mediate urotensin II-induced stimulation of ion transport.