Cracking the neuronal code.
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Biomedical subjects
D Ferster
Publications and source records attributed to D Ferster.
Visually evoked oscillations of membrane potential in cells of cat visual cortex.
In response to visual stimulation, cells of the cat visual cortex fire rhythmically at frequencies between 30 and 60 hertz. This rhythmic firing can be synchronized among cells in widespread areas of the visual cortex. The visual stimulus conditions under which this process occurs suggest that the synchronization may contribute to the integration of information across broadly displaced parts of the visual field. An intricate mechanism must control the regularity of firing and its synchronization. In vivo whole-cell patch recordings from cells in area 17 have now shown that robust oscillations of membrane potential underlie the regularity of firing seen extracellularly. In the cells studied, the characteristics of the oscillations of membrane potential suggest that such oscillations are produced by rhythmic activity in synaptic inputs. These rhythmic synaptic inputs form the most likely mechanism for the synchronization of activity in neighboring cortical cells.
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The synaptic inputs to simple cells of the cat visual cortex.
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EPSP-IPSP interactions in cat visual cortex studied with in vivo whole-cell patch recording.
Postsynaptic inhibition can operate by two distinct mechanisms: (1) membrane hyperpolarization and (2) shunting of excitatory postsynaptic currents. The arithmetic operations--either addition or multiplication--that synapses are able to perform during neuronal computations are determined by which of these two inhibitory mechanisms predominates. Hyperpolarizing IPSPs interact linearly with EPSPs; their negative and positive synaptic currents sum to produce a net change in membrane potential (Eccles, 1961). Shunting synapses interact nonlinearly with EPSPs; the shunt-induced increase in membrane conductance directly reduces the amplitude of EPSPs by a constant multiplicative factor (Fatt and Katz, 1953; Blomfield, 1974). This property of shunting inhibition has provided the basis for models of synaptic interaction in which shunting inhibition acts as an AND-NOT gate for excitatory inputs (Torre and Poggio, 1978; Koch et al., 1983). Using an in vivo variant of the whole-cell patch technique (Blanton et al., 1989), we have examined the effect of visually evoked inhibition on the size of EPSPs in cortical simple cells and found that the predominant inhibitory mechanism is hyperpolarization. We conclude that these inhibitory synapses operate primarily in the linear mode.
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Nonlinearity of spatial summation in simple cells of areas 17 and 18 of cat visual cortex.
1. Nonlinearity of spatial summation in areas 17 and 18 of cat visual cortex was compared with the type of spatial nonlinearity that differentiates X and Y cells in the lateral geniculate nucleus (LGN) and retina. The comparisons were made to examine to what extent the information from X and Y cells may remain separated in higher visual centers. 2. Responses of simple cells in areas 17 and 18 were recorded while stationary, optimally oriented sinewave gratings were sinusoidally modulated within the receptive field of the cell. Both the spatial frequency and spatial phase of the stimulus were varied. 3. Y cells in the retina and LGN are defined by the presence of a specific form of spatial nonlinearity. When tested with contrast-modulated sinewave gratings of spatial frequencies about three-fold greater than the optimal, their responses are dominated by a frequency-doubled component. The amplitude of the frequency-doubled component is not dependent on the spatial phase of the stimulus. 4. Many simple cells in the cortex showed a form of spatial nonlinearity similar to the defining nonlinearity found in retinal and geniculate Y cells. A frequency-doubled response dominated at spatial frequencies more than threefold greater than the optimal spatial frequency. When this response was present, it was phase independent. 5. More than 50% of the simple cells in area 18 showed the Y-like spatial nonlinearity. Fewer than 10% of the simple cells in area 17 showed the Y-like spatial nonlinearity. 6. The virtual absence of Y-like nonlinearity in area 17 and its relative abundance in area 18 suggest that the functional separation between the parallel X and Y pathways remains distinct within areas 17 and 18 of cat visual cortex.
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X- and Y-mediated synaptic potentials in neurons of areas 17 and 18 of cat visual cortex.
When a cuff-shaped electrode is placed on the optic nerve of the cat, X and Y axons, by virtue of their different diameters, exhibit different thresholds to electrical stimulation. Large-diameter Y axons have low thresholds, while smaller-diameter X axons have high thresholds. There is very little overlap between the two populations. Given this segregation, the strength of stimulation of the optic nerve required to evoke synaptic potentials in cortical neurons becomes a reliable indicator of the type of visual input a cortical neuron receives. Potentials with thresholds below the thresholds of X axons must be mediated by Y cells of the retina and LGN. Potentials with thresholds above the Y axons of the optic nerve must be mediated by X cells. From previous experiments, one would expect to find ample input via both types of axon to area 17 of the visual cortex. This was not the case. Of 58 neurons distributed throughout the layers of area 17 from which intracellular records were taken, in only four could substantial Y excitation be detected. Three of these four were located near the border with area 18. All four received large X inputs as well. The 24 neurons studied in area 18 all received large Y inputs but no detectable X input.
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X- and Y-mediated current sources in areas 17 and 18 of cat visual cortex.
X- and Y-mediated input to areas 17 and 18 of the cat visual cortex was studied using current-source-density analysis of field potentials evoked by stimulation of the optic nerves. A cuff-shaped electrode was used for stimulation so that Y axons, by virtue of their larger diameters, would have lower electrical thresholds than X axons. The effect in each cortical area of activating Y axons alone could therefore be determined by low-amplitude stimulation of the optic nerves. Current-source densities were calculated by two separate methods. (1) In five experiments, field potentials were measured sequentially at different cortical depths with a single tungsten electrode. Current densities were then calculated by computer. (2) In two experiments, current densities were derived in real time from field potentials recorded simultaneously from three sites with a multi-electrode probe. The calculation was performed by an analog circuit specially designed for this purpose. This method has several advantages over the standard, single-electrode method. At stimulus strengths sufficient to activate the majority of Y axons in the optic nerves, but subthreshold to most X axons, the field potentials evoked in area 17 changed little from layer to layer. When the current-source-density analysis was applied to these potentials, no significant sources or sinks were detectable. Only when the stimulus strength was raised to the point that both X and Y axons were activated by the stimulus were any current sources or sinks detected in area 17. The currents were similar in time course and laminar pattern to those recorded after stimulation of the optic chiasm. In area 18, large sources and sinks were evoked by stimulation of Y axons alone. These currents changed little when the stimulus strength was increased to activate X axons as well. Area 18, therefore, in contrast to area 17, seems to be dominated by Y input and receives little X input. These results support the conclusions of the accompanying paper in which synaptic potentials were recorded intracellularly from cortical neutrons. The intracellular experiments failed to show substantial Y input to area 17. The projections of X and Y axons may therefore be much more highly segregated into areas 17 and 18 than previously thought. Alternatively, the nature of the Y input to area 17 may be very different from that to area 18 in that it cannot be easily detected with intracellular or current-source-density techniques.
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Binocular convergence of excitatory and inhibitory synaptic pathways onto neurons of cat visual cortex.
When a cortical neuron receives synaptic input from both eyes, do the synaptic pathways that mediate the input from each eye match? In this study, inputs from the two eyes were compared by measuring the latencies of EPSPs and IPSPs evoked by electrical stimulation of the two optic nerves. For binocular neurons, these latencies invariably matched closely, indicating that the pathways from the two eyes contain the same number of synapses; monosynaptic input from lamina A of the lateral geniculate nucleus (LGN) is always matched by monosynaptic input from lamina A1. Conversely, polysynaptic input from one eye, either excitatory or inhibitory, is invariably accompanied by similar input from the other eye. In addition, the match between the two eyes in latency indicates that for each eye a synaptic potential is mediated by the same type of afferent, either X or Y. Judging from intracellular recording, 75% of the neurons studied were binocular, that is, EPSPs could be evoked from either eye. In the remaining 25%, EPSPs could be evoked from only one eye, in agreement with extracellular receptive field studies in which 30% of cortical neurons are monocular.
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Spatially opponent excitation and inhibition in simple cells of the cat visual cortex.
The receptive fields of simple cells in the cat visual cortex are, by definition, divided into ON and OFF subfields. There is little doubt that each subfield is generated by excitatory input from geniculate neurons of the appropriate center type: ON subfields by ON-center cells, and OFF subfields by OFF-center cells. In intracellular records, ON subfields can be detected as regions in which light elicits a barrage of EPSPs, while in OFF subfields, turning a light off does the same. In addition, visual stimuli can evoke strong IPSPs, but these IPSPs have a receptive field spatially opponent to that of the EPSPs: Inhibition is evoked by turning a light off in an ON region and turning a light on in an OFF region. This inhibition probably arises from other cortical simple cells, and may contribute to such receptive-field properties as antagonism between subfields, binocular disparity sensitivity, and orientation selectivity.
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Origin of orientation-selective EPSPs in simple cells of cat visual cortex.
According to current theory, orientation selectivity in cortical simple cells is critically dependent on intracortical synaptic inhibition. In particular, it is thought that IPSPs evoked by stimuli of the nonpreferred orientation are required to prevent a neuron from responding to a broadly tuned excitatory input at any but the preferred orientation. Yet EPSPs recorded in simple cells are in themselves highly orientation-selective. How is this possible, when excitation arises primarily from relay cells of the lateral geniculate nucleus (LGN), which are largely insensitive to orientation? In this paper, the properties of EPSPs are compared with the predictions of a model of geniculate excitation of simple cells. The model, which is derived from the suggestions of Hubel and Wiesel (1962), relies on the now familiar arrangement of the receptive fields of presynaptic geniculate cells into lines parallel to the axis of orientation of the postsynaptic cell. Several properties of the EPSPs observed in simple cells, and the orientation tuning of simple cells observed in extracellular experiments, can be accounted for without resorting to intracortical inhibition.
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Orientation selectivity of synaptic potentials in neurons of cat primary visual cortex.
Neurons of the visual cortex of the cat were penetrated with intracellular electrodes and postsynaptic potentials evoked by visual stimuli recorded. By alternately polarizing the cell with steady current injected through the recording electrode, IPSPs and EPSPs could be recorded and analyzed independently. Hyperpolarizing current suppressed IPSPs and enhanced EPSPs by moving the membrane potential toward the IPSP equilibrium potential. Depolarizing the cell toward the EPSP equilibrium potential enhanced IPSP. The responses to electrical stimulation of the LGN, where EPSPs and IPSPs could be distinguished easily by virtue of their characteristic latencies and shapes, were used to set the current injection to the appropriate level to view the two types of synaptic potential. EPSPs were found to be well oriented in that maximal depolarizing responses could be evoked at only one stimulus orientation; rotating the stimulus orientation in either direction produced a fall in the EPSP response. IPSPs were also well tuned to orientation, and invariably the preferred orientations of EPSPs and IPSPs in any one cell were identical. In addition, no systematic difference in the width of tuning of the two types of potential was seen. This result has been obtained from penetrations of over 30 cortical cells, including those with simple and complex receptive fields. It is concluded that orientation of cortical receptive fields is neither created nor sharpened by inhibition between neurons with different orientation preference. The function of inhibition evoked simultaneously with excitation by optimally oriented stimuli has yet to be determined, though it is likely to be the mechanism underlying other cortical receptive field properties, such as direction selectivity and end-stopping.
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Augmenting responses evoked in area 17 of the cat by intracortical axon collaterals of cortico-geniculate cells.
Evoked potentials were recorded in the visual cortex of the cat after electrical stimulation of the lateral geniculate nucleus (l.g.n.). The primary response, mediated by geniculo-cortical fibres, was depressed at stimulation frequencies above 7 Hz and replaced by a late potential, the incremental response, which gradually increased in amplitude with successive stimuli. The incremental response was a negative-positive potential in the depth of the cortex with the negative component having maximal amplitude in layer 4. The response reversed polarity in layer 1 to become a positive-negative potential at the surface. The latency of the negative component of the incremental response was about 3.5-4 ms in layer 4, compared to about 1.5 and 2.5 ms for the mono- and disynaptic components of the primary response. The incremental response could only be evoked from the l.g.n. and the optic radiation, not from the optic tract, superior colliculus or other surrounding structures. Within the l.g.n., the effect was only evoked from stimulation sites in approximate retinotopic register with the recording site in the cortex. Low threshold points were found in the A laminae, completely overlapping with the low threshold points for the primary response. Thresholds increased steeply when the stimulation electrode was lowered into the C laminae. The incremental response could still be evoked ten days after the destruction of all cells in the l.g.n. complex by kainic acid. It is concluded that the described incremental response is identical to the augmenting response of Dempsey & Morison (1943) and is mediated by intracortical axon collaterals of antidromically activated cortico-geniculate neurones.
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Synaptic excitation of neurones in area 17 of the cat by intracortical axon collaterals of cortico-geniculate cells.
Antidromic activation of layer 6 cortico-geniculate cells from the lateral geniculate nucleus (l.g.n.) was used to study synaptic effects mediated by their intracortical axon collaterals. A specific stimulation procedure, earlier shown to suppress geniculo-cortical synaptic effects and to enhance synaptic effects from layer 6 cell collaterals was employed to differentiate between inputs from the two pathways. Single cells in different cortical layers were recorded both extra- and intracellularly with glass micro-electrodes. Antidromic activation of cortico-geniculate cells at 10-16 Hz induced massive, usually repetitive, spike discharges in almost all cells in layers 2-5. The shortest latency for this synaptic activation (3.4-7.5 ms) was found for simple cells in layer 4. Cells in layers 2, 3 and 5 responded with progressively longer latencies. Cortico-geniculate cells in layer 6 were atypical in that hardly any responded with synaptic discharges to the stimulation. Intracellular recordings from layer 4 cells revealed, besides a monosynaptic excitatory post-synaptic potential (e.p.s.p.) from geniculo-cortical fibres, a late e.p.s.p. with a latency of 3.0-4.2 ms. This e.p.s.p. could only be evoked from stimulation sites within the A laminae of the l.g.n. in retinotopic register with the recording site in the cortex. No corresponding potential was obtained by stimulation of the optic tract or the superior colliculus. The threshold intensity for the late e.p.s.p. in layer 4 cells was much higher than for the geniculo-cortical e.p.s.p.s from the same stimulation sites, indicating that the effect was mediated by thin fibres. The late e.p.s.p.s increased dramatically in size with repetitive stimulation of the l.g.n. at frequencies above 7 Hz, while the geniculo-cortical e.p.s.p.s remained unchanged. In all these properties, the late e.p.s.p.s resemble similar e.p.s.p.s evoked monosynaptically in principal cells of the l.g.n. by orthodromic activation of cortico-geniculate fibres. Large e.p.s.p.s were evoked also in complex cells of layers 2, 3 and 5 and in simple cells of layer 6 upon antidromic stimulation of cortico-geniculate fibres. The sample included many efferent neurones, identified as projection cells by antidromic activation from extracortical stimulation sites. The latency and behaviour of the e.p.s.p.s in these cells indicate that the effect was mediated indirectly via layer 4 cells. Presumably, the excitation travelled along an earlier identified chain of neurones, going from layer 4 to layers 2 and 3, from there to layer 5 and then to layer 6.(ABSTRACT TRUNCATED AT 400 WORDS)
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An intracellular analysis of geniculo-cortical connectivity in area 17 of the cat.
The latencies of excitatory and inhibitory post-synaptic potentials (e.p.s.p.s and i.p.s.p.s) evoked by electrical stimulation of afferents from the lateral geniculate nucleus were recorded in neurones of area 17 of the cat visual cortex. After application of an extrapolation procedure to compensate for the conduction time of the afferent axons, a histogram of latencies formed three distinct peaks. Potentials in each of these were interpreted as being mediated by mono-, di- and trisynaptic pathways. Characteristic laminar differences in the extracellular field potentials evoked from the lateral geniculate nucleus (l.g.n.) and in the antidromic activation of neurones from the l.g.n. and superior colliculus were used to determine the laminar position of recorded neurones. It was found that within a given layer, all cells maintained similar connexions with relay cells in the l.g.n. Cells in layers 3, 4, upper 5 and 6 were monosynaptically excited by geniculate afferents, while cells in layers 2 and lower 5 received only indirect excitation via other cortical neurones. Layer 3 cells were unique in receiving a prominent disynaptic e.p.s.p. in addition to the direct excitation from the l.g.n. Late, trisynaptic e.p.s.p. components were seen in many layer 5 and 6 cells. The orderly laminar arrangement of the connexions had the consequence that identified cortico-geniculate neurones were monosynaptically excited and cortico-collicular neurones di- and trisynaptically excited by geniculate afferents. Cortico-cortical neurones in layers 2 and 3 received di- or mono- plus disynaptic excitation, depending on laminar position. Post-synaptic inhibitory potentials were evoked in all impaled cells, following stimulation of the geniculo-cortical pathway. Except for a few layer 2 cells, this inhibition was mediated through disynaptic pathways of the feed-forward type. There was a good positive correlation between conduction times for monosynaptic e.p.s.p.s and disynaptic i.p.s.p.s in the same cells, suggesting that cortical neurones receive excitation and inhibition from the same type of geniculate afferents. The stimulating electrodes activated not only geniculo-cortical afferents, but antidromically activated cortical efferent neurones from their extracortical axons. These neurones possess intracortical collaterals, and care must be taken to distinguish the resulting potentials from those mediated by orthodromic activation of geniculate afferents. In doing so, evidence was obtained for excitatory connexions from layers 2 and 3 to layer 5, from layer 5 to layer 6, and from layer 6 to layer 4. Typical recurrent inhibition was not observed.(ABSTRACT TRUNCATED AT 400 WORDS)
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A comparison of binocular depth mechanisms in areas 17 and 18 of the cat visual cortex.
1. The retinal disparity sensitivity of neurones in areas 17 and 18 of the cat visual cortex was examined. The response of each cell to an optimally oriented slit was measured as disparity was varied orthogonally to the receptive field orientation. Eye movements were monitored with a binocular reference cell simultaneously recorded in area 17 (Hubel & Wiesel, 1970).2. Two types of disparity-sensitive cells were found, similar to those observed in the monkey by Poggio & Fischer (1977). The first type, tuned excitatory cells, were usually binocular and had a sharp peak in their disparity-response curve. They responded maximally at the disparity that brought their receptive fields into superposition on the tangent screen. This disparity closely coincided with the disparity at which the reference cell's receptive fields were also superimposed. By analogy with the monkey this point was taken to be the fixation point, or 0 degrees . The second type, near and far cells, were most often monocular. They gave their weakest response (which was usually no response at all) at 0 degrees . On one side of 0 degrees the response grew linearly for up to 4 degrees and then remained at the maximum. On the other side of zero, it remained at the minimum for up to several degrees before rising towards the maximum.3. The receptive field organization of several disparity-sensitive cells was examined using the activity profile method of Henry, Bishop & Coombs (1969). The size and strength of the discrete excitatory and inhibitory regions of the receptive fields of a cell could quantitatively account for the shape of its disparity-response curve.4. The laminar distribution of disparity sensitivity as well as of several other receptive field properties in areas 17 and 18 was studied. The organization of the two areas was remarkably similar in many respects. There was a difference, however, in the proportions of the two types of disparity-sensitive cells in the two areas. Area 17 contained many more tuned excitatory cells than near and far cells, while area 18 had the reverse distribution. In addition, the cells in area 18 were sensitive to a much broader range of disparities. While both areas contain disparity-sensitive neurones, these differences suggest that they play different roles in depth vision.5. Recent psychophysical and neurophysiological evidence has led to a new model of stereopsis in which depth is signalled by the pooled activity of large groups of cells (Richards, 1971). The current results are consistent with this model.
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Proportion of interneurons in the cat's lateral geniculate nucleus.
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The axonal arborizations of lateral geniculate neurons in the striate cortex of the cat.
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Relay cell classes in the lateral geniculate nucleus of the cat and the effects of visual deprivation.
This study presents evidence that the X- and Y-cells described physiologically in the A laminae of the cat's dorsal lateral geniculate nucleus (LGN) are two morphologically distinct cell types recognizable in Golgi preparations. It is shown firstly that the three cell types seen in Golgi preparations of the A laminae (large and medium-sized principal cells and small interneurons-types 1,2 and 3 in the classification of Guillery, '66) may be identified in 1-mum Epon sections of osmicated material. While cell-diameter histograms prepared from serial 1-mum sections show a unimodal distribution of cell sizes, three populations can be distinguished if attention is paid to the presence or absence of large cytoplasmic inclusions (laminar bodies). These three populations consist of large cells lacking laminar bodies (Class I), medium-sized cells possessing laminar bodies (Class II) and small cells lacking them (Class III). That these three classes correspond to the three morphological types has been shown by (i) size comparisons, and (ii) direct demonstration of laminar bodies in the Golgi-impregnated cell bodies of Guillery's type 2 cells. Histograms prepared in this way for samples taken at various positions in the LGN show that the numbers of class II cells decline from the representation of the area centralis to the monocular segment. This decline is compensated by a corresponding rise in the numbers of class I cells. This pattern of distribution is similar to the physiologically observed distribution of X- and Y-cells, indicating that X-cells are likely to be class II cells and Y-cells class I cells. The cortical projections of the various cell types have been examined by the horseradish peroxidase method. Class II cells project to area 17 only. Most class I cells also project to area 17 only, but a few very large class I cells project to area 18. From our results, it appears that very few if any cells in the A laminae have branching axons supplying both 17 and 18. The class III cells do not project to the visual cortex, a finding consistent with their identification as interneurons. Class I and II cells are also found in lamina C and in the MIN. In both these regions there is a predominance of very large class I cells, which project to area 18. Laminae Cl-C3 contain small cells lacking laminar bodies. These cells may project to both areas 17 and 18 with branching axons. They are likely to correspond to Guillery's type 4 cells (small relay cells confined to the C laminae) and to the physiologically described W-cells. Long-term monocular deprivation causes cell shrinkage which is much more severe for class I than for class II cells. There is in addition a decrease in the relative numbers of class I cells. This decrease is found in binocular deprivation also. These observations provide an anatomical basis for the reported loss of Y-cells from deprived laminae of the LGN. It is suggested that the effects of deprivation on Y-cells may be accounted for in terms of competition for synaptic space.
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