The relationship of respiratory sinus arrhythmia amplitude (RSA) to tidal volume and breathing frequency was quantified during voluntarily controlled tidal volume and breathing frequency and spontaneous quiet breathing. Seventeen seated subjects breathed via mouthpiece and nose-clip, maintaining constant tidal volumes at each of several breathing frequencies. Inspiratory breath hold was zero frequency. Log RSA was plotted vs. log frequency for each tidal volume. The large stable RSA for frequencies less than 6 cycles/min was called low-frequency intercept (LFI, 20 +/- 5 beats/min). Low-frequency intercept was inversely proportional to a subject's age only to 35 yr. At higher breathing frequencies above a characteristic corner frequency (fC, 7.2 +/- 1.5 cycles/min) RSA decreased with constant slope (roll-off; 21 +/- 3.4 dB/decade). The RSA-volume relationship was linear permitting normalization of RSA-frequency curves for tidal volume to yield one curve. Spontaneous breathing data points fell on this curve. Voluntarily coupling of heart rate to breathing frequency in integer ratios reduced breath-by-breath variability of RSA without changing mean RSA. In conclusion, low-frequency intercept, corner frequency, and roll-off characterize an individual's RSA-frequency relationship during both voluntarily controlled and spontaneous breathing.

Differential solute clearances were used to characterize glomerular function in 12 nondiabetic subjects with severe obesity (body mass index >38). Nine healthy subjects served as the control group. In the obese group, glomerular filtration rate (GFR) and renal plasma flow (RPF) exceeded the control value by 51 and 31%, respectively. Consequently, filtration fraction increased. The augmented RPF suggested a state of renal vasodilatation involving, mainly or solely, the afferent arteriole. Albumin excretion rate and fractional albumin clearance increased by 89 and 78%, respectively. Oral glucose tolerance tests were suggestive of insulin resistance. Insulin resistance was positively correlated with GFR (r = 0.88, P<0.001) and RPF (r = 0.72, P <0.001). Mean arterial pressure was higher than in the control group. Fractional clearances of dextrans of broad size distribution tended to be lowered. The determinants of the GFR were estimated qualitatively by using a theoretical model of dextran transport through a heteroporous membrane. This analysis suggests that the high GFR in very obese subjects may be the result of an increase in transcapillary hydraulic pressure difference (DeltaP). An abnormal transmission of increased arterial pressure to the glomerular capillaries through a dilated afferent arteriole could account for the augmentation in DeltaP.

Horizontal connections are a principal component of intrinsic cortical circuitry. They arise mainly from pyramidal cells and course parallel to the brain's surface for distances as long as 8 mm, linking columns with shared orientation preference and allowing cells to integrate visual information from outside their receptive fields. We examined the synaptic physiology of the horizontal pathway in slices of the cat's striate cortex and found that activating lateral fibers produced both excitation and inhibition. We recorded the postsynaptic responses of identified pyramidal cells in layer 2 + 3 of area 17 to electrical shocks applied at three sites: in the home column of the impaled neuron either in layer 2 + 3 or 4, or at a lateral distance of 0.9-3 mm in layer 2 + 3. Within the home column, suprathreshold stimuli produced compound EPSPs with action potentials, followed by fast, GABAAergic IPSPs and a slower, GABABergic IPSP. For the distant stimulating site, the threshold response was an EPSP. Stronger shocks frequently evoked a disynaptic, GABAAergic IPSP that truncated the EPSP and could dominate the postsynaptic response. At the resting potential, the horizontally evoked EPSP was too small to elicit spikes. With depolarization of the membrane, however, it grew several hundred-fold. This amplification was blocked by N-(2,6-dimethylphenylcarbamoylmethyl)triethylammonium bromide (QX-314), but not by 2-amino-5-phosphonovalerate (APV), indicating that it was mediated by Na+ channels, rather than by NMDA receptors. We propose that the horizontal connections provide the means for stimuli outside the receptive field to modulate activity elicited within its confines. The voltage-dependent enhancement of the laterally evoked EPSP may explain why stimulating the surround by itself fails to drive cells but can facilitate their response to stimuli within the receptive field. The ability to initiate disynaptic inhibition from lateral sites shows that recruiting appropriate groups of horizontal fibers can also have a suppressive effect. Thus, the effect of horizontal input is state dependent, with the size and sign of the laterally evoked response changing according to the balance of converging inputs.

Simple cells in the visual cortex respond to the precise position of oriented contours (Hubel and Wiesel, 1962). This sensitivity reflects the structure of the simple receptive field, which exhibits two sorts of antagonism between on and off inputs. First, simple receptive fields are divided into adjacent on and off subregions; second, within each subregion, stimuli of the reverse contrast evoke responses of the opposite sign: push-pull (Hubel and Wiesel, 1962;Palmer and Davis, 1981;Jones and Palmer, 1987;Ferster, 1988). We have made whole-cell patch recordings from cat area 17 during visual stimulation to examine the generation and integration of excitation (push) and suppression (pull) in the simple receptive field. The temporal structure of the push reflected the pattern of thalamic inputs, as judged by comparing the intracellular cortical responses to extracellular recordings made in the lateral geniculate nucleus.Two mechanisms have been advanced to account for the pullwithdrawal of thalamic drive and active, intracortical inhibition (Hubel and Wiesel, 1962;Heggelund, 1986;Ferster, 1988). Our results suggest that intracortical inhibition is the dominant, and perhaps sole, mechanism of suppression. The inhibitory influences operated within a wide dynamic range. When inhibition was strong, the membrane conductance could be doubled or tripled. Furthermore, if a stimulus confined to one subregion was enlarged so that it extended into the next, the sign of response often changed from depolarizing to hyperpolarizing. In other instances, the inhibition modulated neuronal output subtly, by elevating spike threshold or altering firing rate at a given membrane voltage. Key words: visual cortex; patch recording in vivo; simple cell; IPSP; EPSP; spiny stellate cellCortical sensitivity to patterned stimuli has its roots in the arrangement of synaptic inputs to simple cells, whose receptive fields are made of elongated, alternating on and off subregions. Bright signals confined to an on subregion are excitatory, whereas dark ones reduce activity; that is, stimuli of the opposite contrast have a push -pull effect (Hubel and Wiesel, 1962;Movshon et al., 1978;Heggelund, 1981Heggelund, , 1986Palmer and Davis, 1981;Jones and Palmer, 1987;Ferster, 1988;Miller, 1994;Troyer et al., 1998; but see Debanne et al., 1998). Furthermore, when the receptive field is uniformly illuminated or darkened, simple cells respond poorly because their subregions have a mutually antagonistic relationship (Hubel and Wiesel, 1962). Thus, the output of the simple cell relies on the balance of excitation and suppression that various stimuli evoke.We have used the technique of whole-cell recording (Hamill et al., 1981;Edwards et al., 1989;Blanton et al., 1989) in vivo (Pei et al., 1991;Ferster and Jagadeesh, 1992) to analyze the synaptic mechanisms that produce visually evoked responses in the receptive field. First, we examined the origins of excitatory and suppressive components of the responses to stimuli of reverse contrast flashed within a single ...

Here we ask whether visual response pattern varies with position in the cortical microcircuit by comparing the structure of receptive fields recorded from the different layers of the cat's primary visual cortex. We used whole-cell recording in vivo to show the spatial distribution of visually evoked excitatory and inhibitory inputs and to stain individual neurons. We quantified the distribution of 'On' and 'Off' responses and the presence of spatially opponent excitation and inhibition within the receptive field. The thalamorecipient layers (4 and upper 6) were dominated by simple cells, as defined by two criteria: they had separated On and Off subregions, and they had push-pull responses (in a given subregion, stimuli of the opposite contrast evoked responses of the opposite sign). Other types of response profile correlated with laminar location as well. Thus, connections unique to each visual cortical layer are likely to serve distinct functions. How does connectivity in striate cortex correlate with receptive field structure and, ultimately, with neural selectivity for elements of the visual scene? Anatomical studies show that each of the six cortical layers has a unique pattern of inputs and outputs 1-4. Thus, it is possible to investigate the function of specific components of the cortical microcircuit by comparing neural response patterns at different laminar positions 5-20. We took this approach to ask whether there are response properties exclusive to the first stage of cortical integration, where new response properties such as orientation sensitivity emerge 12. Early studies suggested that orientation selectivity depends on the structure of the simple receptive field, an arrangement of elongated On and Off subregions with an antagonistic effect on one another 12 , 21-23. This idea came from observations of responses evoked by stimuli placed at different positions in visual space. For instance, a bright contour aligned lengthwise with an On subregion produced strong excitation that diminished when the stimulus was rotated towards the orthogonal angle or was moved sideways to cover larger portions of an adjacent Off subregion 12. The geometry of the simple cell's response was thought to result from an orderly pattern of convergence from On and Off thalamic relay cells 12 , 23-26 .