354
Brain Research, 120 (1977) 354-361 © Elsevier/North-Holland Biomedical Press, Amsterdam - Printed in The Netherlands
The role of visual cortex for binocular interactions in the cat lateral geniculate nucleus*
F. SCHMIELAU and W. SINGER Max-Planck-lnstitut fiir Psychiatrie, Kraepelinstr. 2, 8000 Munich 40 (G.F.R.)
(Accepted October 21st, 1976)
Numerous anatomical studies in various mammals demonstrate an important projection from primary and secondary visual cortex (VC) back to the dorsal lateral geniculate nucleus (LGNd). More recent investigations revealed that this projection is retinotopically organized3,5,14 and originates in layer VI of the VC 4. Comparatively little is known, however, about the functional significance of this corticothalamic pathway. Both excitatory and inhibitory actions on L G N relay cells have been seen after cortical stimulationl~, 1~. But it remained unclear to what extent these effects were attributable to recurrent collaterals of antidromically activated thalamocortical axons rather than to corticofugal fibers. Upon inactivation of the VC by cooling, Kalil and Chase 7 observed only slight alterations of relay cell responses to monocular light stimulation. They suggested that corticofugal fibers are excitatory to relay cells and in addition reduce the efficiency of intrageniculate inhibitory mechanisms. Recent investigations in the cat striate and parastriate cortex have revealed that cells with corticothalamic axons are binocular (unpublished observations). Since binocular interactions are commonly observed already at the L G N leveP, 12,18it seemed appropriate to reinvestigate the function of corticofugal fibers in this special context. A preliminary account of the present data has been given in ref. 11. Corticofugal influence was assessed by comparing the activity of single units in the LGN under normal conditions and when visual cortex had been reversibly inactivated by cooling. All experiments were performed on adult cats. For surgery the animals were anesthetized with thiopental sodium (Pentothal®); during the recording period they were immobilized with a continuous infusion of gallamine triethiodide (Flaxedil®) and anesthetized with nitrous oxide (70~o NzO-30~o 02). EEG, body temperature, COz concentration in the expired air and heart rate were continuously monitored. Fluid balance was maintained by i.v. infusion of a glucose-Ringer solution. The pupils were dilated with atropine and the corneae were protected with opaque contact lenses containing artificial pupils of 2 mm in diameter. The refraction of the eyes was measured with a Rodenstock refractometer and corrected, if necessary, with
* This work has been partially supported by the Deutsche Forschungsgemeinschaft,SFB 50, A 1.4.
355 spectacle lenses. The eyes were then inspected with a fundus camera and retinal landmarks were plotted on a white tangent screen 1.5 m distant. The position of these landmarks was repeatedly verified throughout the experiment. For simultaneous but independent stimulation of both eyes, the visual axis of the respective dominant eye was deflected by 30° with a prism. Single unit activity was recorded from layers A and A1 of the L G N with potassium citrate (1.5 mole/liter) filled micropipettes (impedance at 300 c/sec from 5 to 10 M ~ ) . Relay cells were identified as X or Y type from their responses to light stimuli and from their reaction to electrical stimulation of the optic chiasm (OX). The exposed parts (Fig. 1A) of visual areas 17 and 18 were reversibly inactivated by cooling. The cooling device consisted of a 2 mm thick silver plate which was shaped to precisely fit the exposed cortical surface. After this plate had been cemented to the surrounding bone a copper chamber was attached to a prefabricated cavity in the silver plate. Before cooling and for rapid rewarming after cooling the chamber was perfused with water the temperature of which was kept constantly at the level of the animal's core temperature by an electronically controlled heater. For cooling the chamber was perfused with methanol which had a constant temperature of 0.2 °C. In none of the experiments more than 3 cooling cycles were applied to minimize irreversible cortical damage. The efficiency of cortical cooling was judged from the depression of the E E G and the disappearance of postsynaptic components in the evoked potential which was elicited from OX (Fig. 1B). The EEG was recorded from area 18 with a silver ball electrode located below the cooling device. The time that elapsed between the onset of cooling and the disappearance of postsynaptic components in the evoked potential ranged between 4 and 5 min. We then allowed for another 10 rain of cooling before measurements were started. Recovery time after cooling was consistently longer. Complete restoration of the evoked potential occurred only after 30-60 min. As indicated in Fig. 1C, restoration of L G N unit responses to precool levels was usually faster and occurred already 10-20 min after the end of cooling. This suggests that the deep cortical layers which contain the cells with corticofugal axons recover faster than the superficial layers. To make sure that the cooling procedure led to reliable inactivation of cortical responses without directly affecting units in the LGN, temperature gradients were repeatedly measured in 6 different cats. For that purpose a miclo-thermistor probe (diameter 0.5 mm) was either inserted through a hole in the silver plate into the underlying area 18 or it was lowered along the recording track of the microelectrode down to the LGN. In the latter case temperature measurements were taken in steps of 1 mm. The time course of temperature changes in the cortex underlying the silver plate is shown in Fig. 1E. For these measurements the thermistor needle was inserted 5 mm deep into area 18 at the site indicated by the star in Fig. 1A. It can be seen that steadystate temperature ¢.f28 °C is obtained 10 min after the onset of cooling. The time course of rewarming after the end of cooling is slower as shown by the squares in Fig. 1E. As exemplified in Fig. 1D steady-state temperatures ranged between 5 and 8 °C at a depth of 500 #m, between 10-12 °C at 1.0 mm and 15-18 °C at 2.0 mm. This corresponds to an average temperature gradient right under the cooling probe of approximately
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Fig. 1. A: schematic presentation of the dorsal view of the cat's right hemisphere according to ReinosoSuarez s. LAT, lateral sulcus; SUPS, suprasylvian sulcus. Stippled region indicates cooled area. B: cortical evoked potentials after electrical stimulation of optic chiasm (OX) under normal conditions, during cortical cooling and 30 rain after the end of cooling. Negative potentials are shown as upward deflections. Horizontal calibration: 1 msec; vertical calibration: 25 #V. Numbers 1, 2 indicate presynaptic, numbers 3-5 postsynaptic components. C: response of an on-center L G N relay cell to a stationary flashed spot of light (diameter 7.5 °, duration 500 msec) before, during and 20 rain after the end of cortical cooling. The response histograms are compiled from 20 stimulus presentations and show the full reversibility of the effects of cortical cooling. D: depth dependent temperature gradients determined 15 min after the onset of cooling right under the cooling probe in area 18 (tilled circles) and along the recording track (open circles). The sites of thermistor penetrations are indicated by the star and the triangle in A. Abscissa: temperature in °C. Ordinate: depth from cortical surface in mm. E: time course of temperature changes after the onset (filled circles) and offset (squares) of cooling measured at a depth of 5 m m under the cooling probe in area 18. Ordinate: time after on- and offset of cooling. Abscissa: temperature in °C.
357 5 °C/mm. Similar values were found by Kalil and Chase 7. It can be inferred from these data that cooling is reliably inactivating the cortical region below the probe within approximately 5-10 min. This corresponds to the time course of the evoked potential changes. The temperature profiles along the recording track to the L G N showed that direct cooling effects in the L G N or in the overlying nucleus reticularis thalami can be safely excluded. Temperature in this region was normal as indicated by the open circles in Fig. 1D. To further convince ourselves that cooling had specifically affected the feedback loops from areas 17 and 18, in one pilot study the cooling device was placed over the suprasylvian gyrus which is physically even closer to the LGN. But none of the effects described in this study were observed after cooling these cortical areas. Since the common arrangement of the cooling device allowed reliable inactivation only of those cortical cells which possess receptive fields close to the vertical meridian, only those L G N cells were analyzed whose RFs were close to the horizontal meridian and whose eccentricity from area centralis was below 10°. For 28 neurons in lamina A and A1 of the L G N d the following parameters of cell activity were routinely determined: (1) the spontaneous activity, (2) the response to stationary light spots of variable diameters which were flashed in the receptive field center of the dominant eye (RFCd), (3) the responses to binocular stimulation, whereby the corresponding receptive field of the non-dominant eye (RFnd) was stimulated either alone or simultaneously with the RFCd. All of the analyzed neurons could be excited only from the dominant eye. But with active cortex 21 of these cells showed binocular interactions. In 4 of them stimulation of the RFnd was purely inhibitory both on spontaneous activity and on responses evoked from the RFCd. In the remaining 17 cells stimuli in the non-dominant eye were either facilitatory or inhibitory depending upon the site of stimulation within the RFnd. In these cases the spatial organization of the RFnd was closely resembling the concentrically organized receptive field in the dominant eye. When the stimulus was shone into a small central region of the RFnd it facilitated the response to stimulation of the RFCd. Stimulation of the surrounding area resulted in inhibition of the responses elicited from the RFCd. The diameter of the central facilitatory region was comparable to that of the respective RFCd (0.5-2°), and the diameter of the inhibitory region was similar to that of the inhibitory surround of the RFCd (5°-10°). An example for such a structured RF in the nondominant eye is shown in Fig. 2. This X type on-center cell was located in the middle of lamina A1 and responded with a latency of 2.0 msec to OX stimulation. Stimulation of the RFCd (O -- 1°) with a spot of light ( ~ = 40') elicited a sluggish, sustained onresponse (Fig. 2A). Simultaneous stimulation of the center region of the RFnd with a spot o f 1° in diameter caused a strong increase of the initial ON response without noticeably affecting the tonic phase of the response (Fig. 2B). This facilitation had a latency of 30 msec and lasted 120 msec. Stimulation of adjacent positions within the R F n d led to a reduction of the initial on-response, again leaving the later tonic phase unaffected (Fig. 2C). Thus, the time course of the inhibition was similar to that of the facilitation. The results of a detailed field mapping of the RFnd are summarized in Fig. 2G. Stimulus positions in the RFnd are indicated by circles and the numbers indicate the changes in per cent of the binocular on-responses relative to the amplitude
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Fig. 2. Poststimulus time histograms (PSTHs) (20 repetitions, bin width 10 msec) from X-on-center neuron in lamina A1 to monocular and binocular stimulation with stationary flashed spots of light. Responses in A - C are obtained under normal conditions and responses D - F during cortical cooling. A, D: responses to a stationary spot of light (o = 40', duration -- 1 sec) shone into the receptive field center of the dominant (ipsilateral) eye (RFCd). Stimulus duration is indicated by upward deflection of black bar below the PSTHs. B, E: together with the stimulus in the RFCd a spot of light (o -- 1°, duration = 1 sec) is shone into the central part of the receptive field in the non-dominant (contralateral) eye (RFnd). C, F: simultaneously with stimulation of the RFCd a spot of light (o = 1°) is shone in the surround of the RFnd. G, H: schematical representation of the RFnd. Circles refer to stimulus positions within RFnd. Hatched region indicates central part of the RFnd. The numbers on the various stimulation sites within the RFnd correspond to the change ( ~ ) of the respective binocular response amplitudes relative to the responses elicited from the dominant eye alone. Only the first 120 msec from the onset of the responses are considered. The percentages in G are calculated from responses obtained with active cortex and the percentages in H were obtained during cortical cooling.
359 of the monocular response which is elicited by RFCd stimulation. Only the first 120 msec of the respective on-responses are considered. The responses to each of the 9 binocular stimulation conditions were tested in two different sequences. Thus, two temporally independent histograms from 20 stimulus presentations each were compiled for every stimulus position. The monocular control responses from the dominant eye alone were obtained from 5 histograms which were compiled at the beginning, at the end and between the two sequences of binocular stimulation. The variability of corresponding responses was below 10 ~ . The per cent values in Fig. 2G were calculated from the mean response amplitudes as determined from the 5 monocular and the 18 binocular response histograms. Such structured receptive fields in the non-dominant eye were observed in on- and off-center relay cells in both laminae A and A1. The facilitation occurred for the onresponse in on-center cells and for the off-response in off-center cells. The latency of this facilitation from the non-dominant eye ranged from 30 to 180 msec and its duration varied between 60 and 600 msec. The inhibition from the RFnd occurred with latencies between 50 and 80 msec and lasted from 60 to 230 msec. Stimulation of the non-dominant RF alone caused a modulation of spontaneous activity whereby the inhibitory effect was predominant. The resting activity could be reduced by as much as 85 ~ . When the RFnd was stimulated with moving slits of light, the inhibition was occasionally interrupted by a brief phase of reduced inhibition during which the cells' activity could return to the level of spontaneous discharge rate. This brief phase corresponded approximately to the passage of the moving stimulus over the center region of the RFnd. When the RFnd was mapped with stationary stimuli, spots shone into the center region of the RFnd tended to cause less inhibition than adjacent stimuli. Nine cells with structured RFs in the non-dominant eye could be analyzed successfully also during cortical cooling. In 5 cells the inactivation of the corticofugal projection resulted in a complete abolition of the facilitation from the center region of the RFnd. In 2 of these 5 cells also the inhibition from the RFnd was no longer elicitable, and in the remaining 3 cells binocular inhibition was reduced by about 71 ~o. In 4 cells with purely inhibitory RFs in the non-dominant eye cortical cooling abolished the inhibition in two cases and reduced it by 64 ~o in the other two neurons. The light responses in Fig. 2 D - F are obtained with the same stimulation conditions as those in Fig. 2A-C but during cortical cooling. Cortical inactivation resulted in a reduction of the response to monocular stimulation of the dominant eye by 12 (Fig. 2D) although spontaneous activity had slightly increased. This reduction of responses to stimulation of the RFCd was also observed in 70 ~ of the on-center cells investigated in another context (see Fig. 1C and ref. 10) and is in line with the results of Kalil and Chase 7. It supports the hypothesis that corticofugal fibers facilitate L G N relay cells. As exemplified in Fig. 2E cortical cooling had in addition abolished the facilitation which could be elicited previously from the center region of the RFnd. From this area now only inhibitory effects could be obtained. The formerly inhibitory regions in the R F n d were now less effective (Fig. 2F). The graph in Fig. 2H summarizes quantitatively the sensitivity profile of the RFnd as it appears during cortical in-
360 activation. It is calculated in the same way and from the same sequence of stimulus presentations as the corresponding graph in Fig. 2G. These data suggest that corticofugal fibers are involved both in facilitatory and inhibitory binocular interactions. Binocular facilitation seems to be conveyed exclusively by the cortical loop. The fact that binocular inhibition is not always abolished completely during cortical inactivation indicates, however, that binocular inhibition also depends upon intrageniculate circuits. This is in line with previous findings a,lz. If one considers the strictly retinotopic organization of the thalamo-corticothalamic loop and the response properties of binocular cortical cells, both binocular facilitation and inhibition of L G N cells can be accounted for by a uniform action of the corticofugal fibers. This action is likely to consist of a local facilitation of relay cells and a blockade of binocular inhibition within the respective projection column. When only one eye is stimulated, binocular cells with corticofugal axons are probably only little excited (refs. l, 12 and unpublished observations). Consequently the cells in the lamina connected to the non-dominant eye will be mainly influenced by intrageniculate binocular inhibition. This is what was observed when only the nondominant eye was stimulated. In that case there was never a prominent facilitatory effect from the RFnd. When both eyes are stimulated simultaneously at precisely corresponding retinal areas, the binocular corticofugal cells are likely to be strongly activatedl,2, 6. As this study has shown this iesults in blockade of binocular inhibition in the corresponding projection column in the L G N and in additional facilitation of the relay cells therein. When the two stimuli are out of register it can be assumed that binocular cortical cells are not only not excited but even inhibited 1,2. This would then reduce a tonic facilitatory or disinhibitory effect of corticofugal fibers in the projection columns excited by misaligned stimuli. Such a disfacilitation could explain that the inhibitory effect of misaligned stimuli in the non-dominant eye was relatively stronger when the cortex was active than when the cortex was cooled. With active cortex both interlaminar binocular inhibition and corticofugal disfacilitation add together whereas after cortical inactivation only intrageniculate inhibition is effective. Thus, in summary, the present results suggest that one function of the corticofugal projection to L G N d is to adjust in a strictly retinotopic way the threshold of L G N relay cells within a projection column as a function of binocular disparity. Binocularly viewed stimuli which are located on the horopter plane inactivate the intrinsic binocular inhibition within the respective L G N projection column. The responses from both eyes are facilitated and relayed in a symmetrical way to cortex. Activity from stimuli located in front of or behind the horopter plane is subject to binocular inhibition in the respective projection columns. The corticofugal control of binocular interactions in the L G N is thus facilitating transmission of binocular signals from contours which are on the fixation plane whereas signals from objects outside the fixation plane are reduced. Such a mechanism seems appropriate to enhance selectively the transmission of those binocular signals which can be fused and evaluated in terms of depth cues. By contrast, those binocular signals which cannot be fused and would give rise to
361 d o u b l e i m a g e s get s u p p r e s s e d because o f the c o m b i n e d a c t i o n o f i n t e r l a m i n a r i n h i b i t i o n a n d a d d i t i o n a l c o r t i c o f u g a l disfacilitation. Because o f the reciprocal i n t e r l a m i n a r i n h i b i t o r y c o n n e c t i o n s it m a y be s p e c u l a t e d t h a t activity f r o m one eye is r e l a y e d p r e f e r e n t i a l l y whereas signals f r o m the o t h e r eye get r e d u c e d when b i n o c u l a r l y viewed p a t t e r n s are o u t o f register. Thus, the saliency o f the b a c k g r o u n d gets r e d u c e d a n d the signals f r o m objects on the fixation p l a n e b e c o m e facilitated. T h e c o m b i n e d a c t i o n o f intrinsic L G N inh i b i t i o n a n d c o r t i c o f u g a l c o n t r o l is, therefore, i m p r o v i n g the c o n t r a s t between figure and ground.
1 Barlow, H. C., Blakemore, C. and Pettigrew, I. D., The neural mechanism of binocular depth discrimination, J. Physiol. (Lond.), 193 (1967) 327-342. 2 Bishop, P. O., Henry, G. H. and Smith, C. J., Binocular interaction fields of single units in the cat striate cortex, J. Physiol. (Lond.), 216 (1971) 39-68. 3 Garey, L. J., Jones, E. G. and Powell, T. P. S., Interrelationships of striate and extrastriate cortex with the primary relay sites of the visual pathway, J. Neurol. Neurosurg. Psychiat., 31 (1968) 135-157. 4 Gilbert, C. D. and Kelly, J. P., The projection of cells in different layers of the cat's visual cortex, J. comp. Neurol., 163 (1975) 81-105. 5 Holl/inder, H., Autoradiographic evidence for a projection from the striate cortex to the dorsal part of the lateral geniculate nucleus in the cat, Brain Research, 41 (1972) 464-466. 6 Hubel, D. H. and Wiesel, T. N., Receptive fields, binocular interaction and functional architecture in the cat's visual cortex, J. Physiol. (Lond.), 160 (1962) 106-154. 7 Kalil, R. E. and Chase, R., Corticofugal influence on activity of lateral geniculate neurons in the cat, J. NeurophysioL, 33 (1970) 459-474. 8 Reinoso-Suarez, R., Topografischer Hirnatlas der Katze, Merck, Darmstadt, 1961. 9 Sanderson, K. J., Bishop, P. O. and Darian-Smith, I., The properties of the binocular receptive fields of lateral geniculate neurons, Exp. Brain Res., 13 (1971) 178-207. 10 Schmielau, F. and Singer, W., Corticofugal control of the cat lateral geniculate nucleus, Exp. Brain Res., 23 (1975) 363. 11 Schmielau, F. and Singer, W., Cortical influence on binocular interaction in cat lateral geniculate nucleus, Pfliigers Arch. ges. PhysioL, 362, Suppl. (1976) R43, 171. 12 Singer• w.• •nhibit•ry bin•cu•ar interacti•n in the •atera• genicu•ate b•dy •f the cat• Brain Research• 18 (1970) 165-170. 13 Suzuki, H. and Kato, E., Binocular interaction at cat's geniculate body, d. NeurophysioL, 29 (1966) 909-920. 14 Updyke, B. V., The patterns of projection of cortical areas 17, 18 and 19 onto the laminae of the dorsal lateral geniculate nucleus in the cat, J. comp. Neurol., 163 (1975) 377-395. 15 Vastola, E. F., Steady state effects of visual cortex on geniculate cells, Vision Res., 7 (1967) 599-609. 16 Wid6n, L. and Ajmone Marsan, C., Effects of corticopetal and corticofugal impulses upon single elements of the dorsolateral geniculate nucleus, Exp. Neurol., 2 (1960) 468-502.
Brain Research, 120 (1977) 354-361 © Elsevier/North-Holland Biomedical Press, Amsterdam - Printed in The Netherlands
The role of visual cortex for binocular interactions in the cat lateral geniculate nucleus*
F. SCHMIELAU and W. SINGER Max-Planck-lnstitut fiir Psychiatrie, Kraepelinstr. 2, 8000 Munich 40 (G.F.R.)
(Accepted October 21st, 1976)
Numerous anatomical studies in various mammals demonstrate an important projection from primary and secondary visual cortex (VC) back to the dorsal lateral geniculate nucleus (LGNd). More recent investigations revealed that this projection is retinotopically organized3,5,14 and originates in layer VI of the VC 4. Comparatively little is known, however, about the functional significance of this corticothalamic pathway. Both excitatory and inhibitory actions on L G N relay cells have been seen after cortical stimulationl~, 1~. But it remained unclear to what extent these effects were attributable to recurrent collaterals of antidromically activated thalamocortical axons rather than to corticofugal fibers. Upon inactivation of the VC by cooling, Kalil and Chase 7 observed only slight alterations of relay cell responses to monocular light stimulation. They suggested that corticofugal fibers are excitatory to relay cells and in addition reduce the efficiency of intrageniculate inhibitory mechanisms. Recent investigations in the cat striate and parastriate cortex have revealed that cells with corticothalamic axons are binocular (unpublished observations). Since binocular interactions are commonly observed already at the L G N leveP, 12,18it seemed appropriate to reinvestigate the function of corticofugal fibers in this special context. A preliminary account of the present data has been given in ref. 11. Corticofugal influence was assessed by comparing the activity of single units in the LGN under normal conditions and when visual cortex had been reversibly inactivated by cooling. All experiments were performed on adult cats. For surgery the animals were anesthetized with thiopental sodium (Pentothal®); during the recording period they were immobilized with a continuous infusion of gallamine triethiodide (Flaxedil®) and anesthetized with nitrous oxide (70~o NzO-30~o 02). EEG, body temperature, COz concentration in the expired air and heart rate were continuously monitored. Fluid balance was maintained by i.v. infusion of a glucose-Ringer solution. The pupils were dilated with atropine and the corneae were protected with opaque contact lenses containing artificial pupils of 2 mm in diameter. The refraction of the eyes was measured with a Rodenstock refractometer and corrected, if necessary, with
* This work has been partially supported by the Deutsche Forschungsgemeinschaft,SFB 50, A 1.4.
355 spectacle lenses. The eyes were then inspected with a fundus camera and retinal landmarks were plotted on a white tangent screen 1.5 m distant. The position of these landmarks was repeatedly verified throughout the experiment. For simultaneous but independent stimulation of both eyes, the visual axis of the respective dominant eye was deflected by 30° with a prism. Single unit activity was recorded from layers A and A1 of the L G N with potassium citrate (1.5 mole/liter) filled micropipettes (impedance at 300 c/sec from 5 to 10 M ~ ) . Relay cells were identified as X or Y type from their responses to light stimuli and from their reaction to electrical stimulation of the optic chiasm (OX). The exposed parts (Fig. 1A) of visual areas 17 and 18 were reversibly inactivated by cooling. The cooling device consisted of a 2 mm thick silver plate which was shaped to precisely fit the exposed cortical surface. After this plate had been cemented to the surrounding bone a copper chamber was attached to a prefabricated cavity in the silver plate. Before cooling and for rapid rewarming after cooling the chamber was perfused with water the temperature of which was kept constantly at the level of the animal's core temperature by an electronically controlled heater. For cooling the chamber was perfused with methanol which had a constant temperature of 0.2 °C. In none of the experiments more than 3 cooling cycles were applied to minimize irreversible cortical damage. The efficiency of cortical cooling was judged from the depression of the E E G and the disappearance of postsynaptic components in the evoked potential which was elicited from OX (Fig. 1B). The EEG was recorded from area 18 with a silver ball electrode located below the cooling device. The time that elapsed between the onset of cooling and the disappearance of postsynaptic components in the evoked potential ranged between 4 and 5 min. We then allowed for another 10 rain of cooling before measurements were started. Recovery time after cooling was consistently longer. Complete restoration of the evoked potential occurred only after 30-60 min. As indicated in Fig. 1C, restoration of L G N unit responses to precool levels was usually faster and occurred already 10-20 min after the end of cooling. This suggests that the deep cortical layers which contain the cells with corticofugal axons recover faster than the superficial layers. To make sure that the cooling procedure led to reliable inactivation of cortical responses without directly affecting units in the LGN, temperature gradients were repeatedly measured in 6 different cats. For that purpose a miclo-thermistor probe (diameter 0.5 mm) was either inserted through a hole in the silver plate into the underlying area 18 or it was lowered along the recording track of the microelectrode down to the LGN. In the latter case temperature measurements were taken in steps of 1 mm. The time course of temperature changes in the cortex underlying the silver plate is shown in Fig. 1E. For these measurements the thermistor needle was inserted 5 mm deep into area 18 at the site indicated by the star in Fig. 1A. It can be seen that steadystate temperature ¢.f28 °C is obtained 10 min after the onset of cooling. The time course of rewarming after the end of cooling is slower as shown by the squares in Fig. 1E. As exemplified in Fig. 1D steady-state temperatures ranged between 5 and 8 °C at a depth of 500 #m, between 10-12 °C at 1.0 mm and 15-18 °C at 2.0 mm. This corresponds to an average temperature gradient right under the cooling probe of approximately
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Fig. 1. A: schematic presentation of the dorsal view of the cat's right hemisphere according to ReinosoSuarez s. LAT, lateral sulcus; SUPS, suprasylvian sulcus. Stippled region indicates cooled area. B: cortical evoked potentials after electrical stimulation of optic chiasm (OX) under normal conditions, during cortical cooling and 30 rain after the end of cooling. Negative potentials are shown as upward deflections. Horizontal calibration: 1 msec; vertical calibration: 25 #V. Numbers 1, 2 indicate presynaptic, numbers 3-5 postsynaptic components. C: response of an on-center L G N relay cell to a stationary flashed spot of light (diameter 7.5 °, duration 500 msec) before, during and 20 rain after the end of cortical cooling. The response histograms are compiled from 20 stimulus presentations and show the full reversibility of the effects of cortical cooling. D: depth dependent temperature gradients determined 15 min after the onset of cooling right under the cooling probe in area 18 (tilled circles) and along the recording track (open circles). The sites of thermistor penetrations are indicated by the star and the triangle in A. Abscissa: temperature in °C. Ordinate: depth from cortical surface in mm. E: time course of temperature changes after the onset (filled circles) and offset (squares) of cooling measured at a depth of 5 m m under the cooling probe in area 18. Ordinate: time after on- and offset of cooling. Abscissa: temperature in °C.
357 5 °C/mm. Similar values were found by Kalil and Chase 7. It can be inferred from these data that cooling is reliably inactivating the cortical region below the probe within approximately 5-10 min. This corresponds to the time course of the evoked potential changes. The temperature profiles along the recording track to the L G N showed that direct cooling effects in the L G N or in the overlying nucleus reticularis thalami can be safely excluded. Temperature in this region was normal as indicated by the open circles in Fig. 1D. To further convince ourselves that cooling had specifically affected the feedback loops from areas 17 and 18, in one pilot study the cooling device was placed over the suprasylvian gyrus which is physically even closer to the LGN. But none of the effects described in this study were observed after cooling these cortical areas. Since the common arrangement of the cooling device allowed reliable inactivation only of those cortical cells which possess receptive fields close to the vertical meridian, only those L G N cells were analyzed whose RFs were close to the horizontal meridian and whose eccentricity from area centralis was below 10°. For 28 neurons in lamina A and A1 of the L G N d the following parameters of cell activity were routinely determined: (1) the spontaneous activity, (2) the response to stationary light spots of variable diameters which were flashed in the receptive field center of the dominant eye (RFCd), (3) the responses to binocular stimulation, whereby the corresponding receptive field of the non-dominant eye (RFnd) was stimulated either alone or simultaneously with the RFCd. All of the analyzed neurons could be excited only from the dominant eye. But with active cortex 21 of these cells showed binocular interactions. In 4 of them stimulation of the RFnd was purely inhibitory both on spontaneous activity and on responses evoked from the RFCd. In the remaining 17 cells stimuli in the non-dominant eye were either facilitatory or inhibitory depending upon the site of stimulation within the RFnd. In these cases the spatial organization of the RFnd was closely resembling the concentrically organized receptive field in the dominant eye. When the stimulus was shone into a small central region of the RFnd it facilitated the response to stimulation of the RFCd. Stimulation of the surrounding area resulted in inhibition of the responses elicited from the RFCd. The diameter of the central facilitatory region was comparable to that of the respective RFCd (0.5-2°), and the diameter of the inhibitory region was similar to that of the inhibitory surround of the RFCd (5°-10°). An example for such a structured RF in the nondominant eye is shown in Fig. 2. This X type on-center cell was located in the middle of lamina A1 and responded with a latency of 2.0 msec to OX stimulation. Stimulation of the RFCd (O -- 1°) with a spot of light ( ~ = 40') elicited a sluggish, sustained onresponse (Fig. 2A). Simultaneous stimulation of the center region of the RFnd with a spot o f 1° in diameter caused a strong increase of the initial ON response without noticeably affecting the tonic phase of the response (Fig. 2B). This facilitation had a latency of 30 msec and lasted 120 msec. Stimulation of adjacent positions within the R F n d led to a reduction of the initial on-response, again leaving the later tonic phase unaffected (Fig. 2C). Thus, the time course of the inhibition was similar to that of the facilitation. The results of a detailed field mapping of the RFnd are summarized in Fig. 2G. Stimulus positions in the RFnd are indicated by circles and the numbers indicate the changes in per cent of the binocular on-responses relative to the amplitude
40
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Fig. 2. Poststimulus time histograms (PSTHs) (20 repetitions, bin width 10 msec) from X-on-center neuron in lamina A1 to monocular and binocular stimulation with stationary flashed spots of light. Responses in A - C are obtained under normal conditions and responses D - F during cortical cooling. A, D: responses to a stationary spot of light (o = 40', duration -- 1 sec) shone into the receptive field center of the dominant (ipsilateral) eye (RFCd). Stimulus duration is indicated by upward deflection of black bar below the PSTHs. B, E: together with the stimulus in the RFCd a spot of light (o -- 1°, duration = 1 sec) is shone into the central part of the receptive field in the non-dominant (contralateral) eye (RFnd). C, F: simultaneously with stimulation of the RFCd a spot of light (o = 1°) is shone in the surround of the RFnd. G, H: schematical representation of the RFnd. Circles refer to stimulus positions within RFnd. Hatched region indicates central part of the RFnd. The numbers on the various stimulation sites within the RFnd correspond to the change ( ~ ) of the respective binocular response amplitudes relative to the responses elicited from the dominant eye alone. Only the first 120 msec from the onset of the responses are considered. The percentages in G are calculated from responses obtained with active cortex and the percentages in H were obtained during cortical cooling.
359 of the monocular response which is elicited by RFCd stimulation. Only the first 120 msec of the respective on-responses are considered. The responses to each of the 9 binocular stimulation conditions were tested in two different sequences. Thus, two temporally independent histograms from 20 stimulus presentations each were compiled for every stimulus position. The monocular control responses from the dominant eye alone were obtained from 5 histograms which were compiled at the beginning, at the end and between the two sequences of binocular stimulation. The variability of corresponding responses was below 10 ~ . The per cent values in Fig. 2G were calculated from the mean response amplitudes as determined from the 5 monocular and the 18 binocular response histograms. Such structured receptive fields in the non-dominant eye were observed in on- and off-center relay cells in both laminae A and A1. The facilitation occurred for the onresponse in on-center cells and for the off-response in off-center cells. The latency of this facilitation from the non-dominant eye ranged from 30 to 180 msec and its duration varied between 60 and 600 msec. The inhibition from the RFnd occurred with latencies between 50 and 80 msec and lasted from 60 to 230 msec. Stimulation of the non-dominant RF alone caused a modulation of spontaneous activity whereby the inhibitory effect was predominant. The resting activity could be reduced by as much as 85 ~ . When the RFnd was stimulated with moving slits of light, the inhibition was occasionally interrupted by a brief phase of reduced inhibition during which the cells' activity could return to the level of spontaneous discharge rate. This brief phase corresponded approximately to the passage of the moving stimulus over the center region of the RFnd. When the RFnd was mapped with stationary stimuli, spots shone into the center region of the RFnd tended to cause less inhibition than adjacent stimuli. Nine cells with structured RFs in the non-dominant eye could be analyzed successfully also during cortical cooling. In 5 cells the inactivation of the corticofugal projection resulted in a complete abolition of the facilitation from the center region of the RFnd. In 2 of these 5 cells also the inhibition from the RFnd was no longer elicitable, and in the remaining 3 cells binocular inhibition was reduced by about 71 ~o. In 4 cells with purely inhibitory RFs in the non-dominant eye cortical cooling abolished the inhibition in two cases and reduced it by 64 ~o in the other two neurons. The light responses in Fig. 2 D - F are obtained with the same stimulation conditions as those in Fig. 2A-C but during cortical cooling. Cortical inactivation resulted in a reduction of the response to monocular stimulation of the dominant eye by 12 (Fig. 2D) although spontaneous activity had slightly increased. This reduction of responses to stimulation of the RFCd was also observed in 70 ~ of the on-center cells investigated in another context (see Fig. 1C and ref. 10) and is in line with the results of Kalil and Chase 7. It supports the hypothesis that corticofugal fibers facilitate L G N relay cells. As exemplified in Fig. 2E cortical cooling had in addition abolished the facilitation which could be elicited previously from the center region of the RFnd. From this area now only inhibitory effects could be obtained. The formerly inhibitory regions in the R F n d were now less effective (Fig. 2F). The graph in Fig. 2H summarizes quantitatively the sensitivity profile of the RFnd as it appears during cortical in-
360 activation. It is calculated in the same way and from the same sequence of stimulus presentations as the corresponding graph in Fig. 2G. These data suggest that corticofugal fibers are involved both in facilitatory and inhibitory binocular interactions. Binocular facilitation seems to be conveyed exclusively by the cortical loop. The fact that binocular inhibition is not always abolished completely during cortical inactivation indicates, however, that binocular inhibition also depends upon intrageniculate circuits. This is in line with previous findings a,lz. If one considers the strictly retinotopic organization of the thalamo-corticothalamic loop and the response properties of binocular cortical cells, both binocular facilitation and inhibition of L G N cells can be accounted for by a uniform action of the corticofugal fibers. This action is likely to consist of a local facilitation of relay cells and a blockade of binocular inhibition within the respective projection column. When only one eye is stimulated, binocular cells with corticofugal axons are probably only little excited (refs. l, 12 and unpublished observations). Consequently the cells in the lamina connected to the non-dominant eye will be mainly influenced by intrageniculate binocular inhibition. This is what was observed when only the nondominant eye was stimulated. In that case there was never a prominent facilitatory effect from the RFnd. When both eyes are stimulated simultaneously at precisely corresponding retinal areas, the binocular corticofugal cells are likely to be strongly activatedl,2, 6. As this study has shown this iesults in blockade of binocular inhibition in the corresponding projection column in the L G N and in additional facilitation of the relay cells therein. When the two stimuli are out of register it can be assumed that binocular cortical cells are not only not excited but even inhibited 1,2. This would then reduce a tonic facilitatory or disinhibitory effect of corticofugal fibers in the projection columns excited by misaligned stimuli. Such a disfacilitation could explain that the inhibitory effect of misaligned stimuli in the non-dominant eye was relatively stronger when the cortex was active than when the cortex was cooled. With active cortex both interlaminar binocular inhibition and corticofugal disfacilitation add together whereas after cortical inactivation only intrageniculate inhibition is effective. Thus, in summary, the present results suggest that one function of the corticofugal projection to L G N d is to adjust in a strictly retinotopic way the threshold of L G N relay cells within a projection column as a function of binocular disparity. Binocularly viewed stimuli which are located on the horopter plane inactivate the intrinsic binocular inhibition within the respective L G N projection column. The responses from both eyes are facilitated and relayed in a symmetrical way to cortex. Activity from stimuli located in front of or behind the horopter plane is subject to binocular inhibition in the respective projection columns. The corticofugal control of binocular interactions in the L G N is thus facilitating transmission of binocular signals from contours which are on the fixation plane whereas signals from objects outside the fixation plane are reduced. Such a mechanism seems appropriate to enhance selectively the transmission of those binocular signals which can be fused and evaluated in terms of depth cues. By contrast, those binocular signals which cannot be fused and would give rise to
361 d o u b l e i m a g e s get s u p p r e s s e d because o f the c o m b i n e d a c t i o n o f i n t e r l a m i n a r i n h i b i t i o n a n d a d d i t i o n a l c o r t i c o f u g a l disfacilitation. Because o f the reciprocal i n t e r l a m i n a r i n h i b i t o r y c o n n e c t i o n s it m a y be s p e c u l a t e d t h a t activity f r o m one eye is r e l a y e d p r e f e r e n t i a l l y whereas signals f r o m the o t h e r eye get r e d u c e d when b i n o c u l a r l y viewed p a t t e r n s are o u t o f register. Thus, the saliency o f the b a c k g r o u n d gets r e d u c e d a n d the signals f r o m objects on the fixation p l a n e b e c o m e facilitated. T h e c o m b i n e d a c t i o n o f intrinsic L G N inh i b i t i o n a n d c o r t i c o f u g a l c o n t r o l is, therefore, i m p r o v i n g the c o n t r a s t between figure and ground.
1 Barlow, H. C., Blakemore, C. and Pettigrew, I. D., The neural mechanism of binocular depth discrimination, J. Physiol. (Lond.), 193 (1967) 327-342. 2 Bishop, P. O., Henry, G. H. and Smith, C. J., Binocular interaction fields of single units in the cat striate cortex, J. Physiol. (Lond.), 216 (1971) 39-68. 3 Garey, L. J., Jones, E. G. and Powell, T. P. S., Interrelationships of striate and extrastriate cortex with the primary relay sites of the visual pathway, J. Neurol. Neurosurg. Psychiat., 31 (1968) 135-157. 4 Gilbert, C. D. and Kelly, J. P., The projection of cells in different layers of the cat's visual cortex, J. comp. Neurol., 163 (1975) 81-105. 5 Holl/inder, H., Autoradiographic evidence for a projection from the striate cortex to the dorsal part of the lateral geniculate nucleus in the cat, Brain Research, 41 (1972) 464-466. 6 Hubel, D. H. and Wiesel, T. N., Receptive fields, binocular interaction and functional architecture in the cat's visual cortex, J. Physiol. (Lond.), 160 (1962) 106-154. 7 Kalil, R. E. and Chase, R., Corticofugal influence on activity of lateral geniculate neurons in the cat, J. NeurophysioL, 33 (1970) 459-474. 8 Reinoso-Suarez, R., Topografischer Hirnatlas der Katze, Merck, Darmstadt, 1961. 9 Sanderson, K. J., Bishop, P. O. and Darian-Smith, I., The properties of the binocular receptive fields of lateral geniculate neurons, Exp. Brain Res., 13 (1971) 178-207. 10 Schmielau, F. and Singer, W., Corticofugal control of the cat lateral geniculate nucleus, Exp. Brain Res., 23 (1975) 363. 11 Schmielau, F. and Singer, W., Cortical influence on binocular interaction in cat lateral geniculate nucleus, Pfliigers Arch. ges. PhysioL, 362, Suppl. (1976) R43, 171. 12 Singer• w.• •nhibit•ry bin•cu•ar interacti•n in the •atera• genicu•ate b•dy •f the cat• Brain Research• 18 (1970) 165-170. 13 Suzuki, H. and Kato, E., Binocular interaction at cat's geniculate body, d. NeurophysioL, 29 (1966) 909-920. 14 Updyke, B. V., The patterns of projection of cortical areas 17, 18 and 19 onto the laminae of the dorsal lateral geniculate nucleus in the cat, J. comp. Neurol., 163 (1975) 377-395. 15 Vastola, E. F., Steady state effects of visual cortex on geniculate cells, Vision Res., 7 (1967) 599-609. 16 Wid6n, L. and Ajmone Marsan, C., Effects of corticopetal and corticofugal impulses upon single elements of the dorsolateral geniculate nucleus, Exp. Neurol., 2 (1960) 468-502.
