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D Whitteridge

Publications and source records attributed to D Whitteridge.

At least 19 recordsLinked to original sources
PubMed1991

An intracellular analysis of the visual responses of neurones in cat visual cortex.

1. Extracellular and intracellular recordings were made from neurones in the visual cortex of the cat in order to compare the subthreshold membrane potentials, reflecting the input to the neurone, with the output from the neurone seen as action potentials. 2. Moving bars and edges, generated under computer control, were used to stimulate the neurones. The membrane potential was digitized and averaged for a number of trials after stripping the action potentials. Comparison of extracellular and intracellular discharge patterns indicated that the intracellular impalement did not alter the neurones' properties. Input resistance of the neurone altered little during stable intracellular recordings (30 min-2 h 50 min). 3. Intracellular recordings showed two distinct patterns of membrane potential changes during optimal visual stimulation. The patterns corresponded closely to the division of S-type (simple) and C-type (complex) receptive fields. Simple cells had a complex pattern of membrane potential fluctuations, involving depolarizations alternating with hyperpolarizations. Complex cells had a simple single sustained plateau of depolarization that was often followed but not preceded by a hyperpolarization. In both simple and complex cells the depolarizations led to action potential discharges. The hyperpolarizations were associated with inhibition of action potential discharge. 4. Stimulating simple cells with non-optimal directions of motion produced little or no hyperpolarization of the membrane in most cases, despite a lack of action potential output. Directional complex cells always produced a single plateau of depolarization leading to action potential discharge in both the optimal and non-optimal directions of motion. The directionality could not be predicted on the basis of the position of the hyperpolarizing inhibitory potentials found in the optimal direction. 5. Stimulation of simple cells with non-optimal orientations occasionally produced slight hyperpolarizations and inhibition of action potential discharge. Complex cells, which had broader orientation tuning than simple cells, could show marked hyperpolarization for non-optimal orientations, but this was not generally the case. 6. The data do not support models of directionality and orientation that rely solely on strong inhibitory mechanisms to produce stimulus selectivity.

Action Potentials↗
PubMed1991

Mechanisms of inhibition in cat visual cortex.

1. Neurones from layers 2-6 of the cat primary visual cortex were studied using extracellular and intracellular recordings made in vivo. The aim was to identify inhibitory events and determine whether they were associated with small or large (shunting) changes in the input conductance of the neurones. 2. Visual stimulation of subfields of simple receptive fields produced depolarizing or hyperpolarizing potentials that were associated with increased or decreased firing rates respectively. Hyperpolarizing potentials were small, 5 mV or less. In the same neurones, brief electrical stimulation of cortical afferents produced a characteristic sequence of a brief depolarization followed by a long-lasting (200-400 ms) hyperpolarization. 3. During the response to a stationary flashed bar, the synaptic activation increased the input conductance of the neurone by about 5-20%. Conductance changes of similar magnitude were obtained by electrically stimulating the neurone. Neurones stimulated with non-optimal orientations or directions of motion showed little change in input conductance. 4. These data indicate that while visually or electrically induced inhibition can be readily demonstrated in visual cortex, the inhibition is not associated with large sustained conductance changes. Thus a shunting or multiplicative inhibitory mechanism is not the principal mechanism of inhibition.

Action Potentials↗
PubMed1989

Arborisation pattern and postsynaptic targets of physiologically identified thalamocortical afferents in striate cortex of the macaque monkey.

The monosynaptic targets of different functional types of geniculocortical axons were compared in the primary visual cortex of monkeys. Single thalamocortical axons were recorded extracellularly in the white matter by using horseradish-peroxidase-filled pipettes. Their receptive fields were mapped and classified as corresponding to those of parvi- or magnocellular neurons in the lateral geniculate nucleus. The axons were then impaled and injected intraaxonally with horseradish peroxidase. Two magnocellular (MA) and two parvicellular (PA) axons were successfully recovered and reconstructed in three dimensions. The two MA axons arborised mainly in layer 4C alpha, as did the two PA axons in layer 4C beta. Few collaterals formed varicosities in layer 6. Both MA axons had two large, elongated clumps of bouton (approx. 300-500 x 600-1,200 microns each) and a small clump. One PA axon had two clumps (each with a core appr. 200 microns in diameter); the other had only one (appr. 150-200 microns in axon had 1,380; one MA axon had 3,200 boutons; and those of the more extensive MA axon were not counted. The distribution of postsynaptic targets as well as the number of synapses per bouton has been established for a sample of 150 PA boutons and 173 MA boutons from serial ultrathin sections. The MA axons made on average 2.1 synapses per bouton compared to 1.79 for one PA axon and 2.6 for the other. The sample of boutons taken from the two physiological types of axons contacted similar proportions of dendritic spines (52-68%), shafts (33-47%), and somata (0-3%). The postsynaptic elements were further characterized by immunostaining for GABA. All postsynaptic perikarya and some of the dendrites (4.5-9.5% of all targets) were positive for the amino acid. Near the thalamic synapse GABA-negative dendritic shafts frequently contained lamellar bodies, an organelle identical in structure to spine apparatus. Dendritic shafts and spines postsynaptic to the thalamocortical boutons frequently received an adjacent synapse from GABA-immunoreactive boutons. The similarity between the magno-and parvicellular axons in their targeting of postsynaptic elements, including the GABAergic neurons, suggests that the structural basis of the physiological differences between 4C alpha and 4C beta neurons should be sought in other aspects of the circuitry of layer 4C, such as local cortical circuits, or in the far greater horizontal extent of the thalamocortical and GABAergic axons in layer 4C alpha compared to those in the beta subdivision.

Animals↗
PubMed1988

Evidence for the connections between a clutch cell and a corticotectal neuron in area 17 of the cat visual cortex.

Evidence is presented for the synaptic connectivity between a physiologically characterized and intracellularly filled GABAergic interneuron and a corticotectal pyramidal neuron in area 17 of the cat visual cortex. The interneuron was located in layer 4 and had the morphological characteristics of a clutch cell. The physiological data demonstrated that the clutch cell received direct X-type innervation from the dorsal lateral geniculate nucleus. These results indicate that a GABAergic neuron is directly involved during the first cortical stages of geniculocorticotectal interactions. Furthermore, the proximal location of the clutch-cell inputs to the labelled dendrite suggests a strategic siting of intracortical feedforward inhibition.

Animals↗
PubMed1988

Selective responses of visual cortical cells do not depend on shunting inhibition.

Theoretical analyses of the electrical behaviour of the highly branched processes of nerve cells has focused attention on the possibility that single cells perform complex logical operations rather than simply summing their synaptic inputs. In particular, it has been suggested that the orientation and direction selectivity of cells in the visual cortex results from the action of a nonlinear 'shunting' inhibition that emulates an AND-NOT logical operation. The characteristic biophysical feature of this proposed inhibitory mechanism is that it evokes a large and relatively sustained increase in the conductance of the neuronal membrane while leaving the membrane potential unaffected. This shunting mechanism contrasts with linear 'summative' inhibition in which conductance changes are less prominent, and inhibition is achieved by hyperpolarization of the membrane potential. In a direct experimental test of the hypothesis that the selectivity of visual cortical neurons depends on shunting inhibition we found no evidence for the large conductance changes predicted by the theory.

Action Potentials↗
PubMed1988

The dorsal lateral geniculate nucleus of the sheep and its retinal connections.

Layers 1 and 2 of the sheep's LGN have similar properties to layers A and A1 in the cat. In layer 3 of the sheep the cell size is the same as that of the main group in layers 1 and 2, and it is contralaterally driven but has no sublamination. There is a medial interlaminar nucleus in the sheep which consists of two incomplete laminae, each driven by one eye. Scattered cells from the whole of the retina temporal to the decussation line project to the contralateral LGN. There is only a band of cells 1.5 mm wide nasal to the decussation line which project to the ipsilateral LGN. Cells with corresponding ipsilateral fields are found on the medial side of the nucleus in layers 1 and 2. A few cells with orientation sensitivity have been seen in the LGN. The area of the greatest cell density in the retina, the streak, is accommodated in the LGN by expansion vertically, not horizontally.

Animals↗
PubMed1987

Connections between pyramidal neurons in layer 5 of cat visual cortex (area 17).

The structural features of two physiologically-characterised pyramidal neurons (PC1 and PC2) closely situated in layer 5b in the visual cortex (area 17) of a single cat were studied using a combination of electrophysiological and anatomical techniques. Both PC1 and PC2 had exceptionally large somata (30-40 microns in diameter). On the basis of this and other morphological features cell PC1 was classified as a Meynert cell. PC1 possessed a very large (2.75 degrees X 4.50 degrees) binocularly driven standard complex receptive field. PC2 was also binocularly driven with a small, B-type receptive field. Both cells had the same preference for the direction and orientation of visual stimuli. PC1 and PC2 could be antidromically activated from stimulating electrodes positioned above the dorsal lateral geniculate nucleus with a response latency indicating that these cells probably innervated the visual tectum or pretectum. In addition to corticoefferent axons, the two neurons possessed extensive intracortical axon arbors that ramified extensively in layers 5 and 6 of the medial and lateral banks of the lateral gyrus in area 17. Axon collaterals from both PC1 and PC2 also innervated a small common target region in area 18. A total of 313 boutons from the axonal arbors of PC1 and PC2 were examined in the electron microscope. All of the identified synaptic junctions were found to establish Gray type 1 asymmetrical contacts. The combined ultrastructural data for both neurons indicated that 80% of boutons were onto dendritic spine heads, with 14%, 6%, and 1% onto small-, medium-, and large-calibre dendritic shafts, respectively. The spectrum of postsynaptic targets showed little variation with respect to lamina, distance from somata, or cortical area. Other large pyramidal neurons in layer 5 and spiny neurons in layer 6 were identified as receiving synaptic input from either PC1 or PC2. Using a computer graphics system, rotations of the bouton distributions revealed the existence of a clustered innervation of layers 5 and 6 in areas 17 and 18 derived from the two identified neurons. The bouton distributions strongly resembled the tangential pattern described previously for the functional slab-like organisation of the cortex. The results provide a morphological basis for the clustered intrinsic connectivity of pyramidal cells in layers 5 and 6 of the cat visual cortex. Furthermore, the results indicate the widespread excitatory influence of large pyramidal neurons on other cells projecting subcortically to sites dealing with visually guided behavior.

Animals↗
PubMed1986

Synaptic targets of HRP-filled layer III pyramidal cells in the cat striate cortex.

There are numerous hypotheses for the role of the axon collaterals of pyramidal cells. Most hypotheses predict that pyramidal cells activate specific classes of postsynaptic cells. We have studied the postsynaptic targets of two layer III pyramidal cells, that were of special interest because of their clumped axon arborization near, and also 0.4-1.0 mm from the cell body, in register in both layers III and V. 191 terminations from four sites (layers III and V, both in the column of the cell and in distant clumps) were analysed by electron microscopy. Only one bouton contacted a cell body and that was immunoreactive for GABA. The major targets were dendritic spines (84 and 87%), and the remainder were dendritic shafts. Of these 13 were classed as pyramidal-like (P), 8 smooth cell-like (S) and three could not be classified. Four of five S types, but none of the seven P types tested were immunoreactive for GABA, supporting the fine structural classification. The putative inhibitory cells therefore formed not more than 5% of the postsynaptic targets, and their activation could only take place through the convergence of pyramidal cells onto a select population of GABA cells. The results show that the type of pyramidal cells with clumped axons studied here make contacts predominantly with other pyramidal cells. Thus the primary role of both the intra and intercolumnar collateral systems is the activation of other excitatory cells.

Animals↗
PubMed1985

Innervation of cat visual areas 17 and 18 by physiologically identified X- and Y- type thalamic afferents. I. Arborization patterns and quantitative distribution of postsynaptic elements.

Specific thalamic afferents to visual areas 17 and 18 were physiologically classified as X or Y type and injected with horseradish peroxidase (HRP). The axons were examined under the light microscope and were then processed for correlated electron microscopy. X axons arborized in area 17 and in the border between area 17 and 18. The X axons all formed terminals throughout layer 6, but were heterogeneous in their distribution in layer 4. They either occupied the entire width of sublayers 4A and 4B or were strongly biased toward layer 4A. Y axons also arborized in layers 4 and 6, but in area 17 they did not form boutons in sublamina 4B. Some Y axons projected only to area 18; others branched and arborized in both areas 17 and 18. Only the collaterals of one X axons were found to enter area 18; all the others were restricted to area 17. Y axons formed three to four separate patches of boutons about 300-400 microns in diameter, while all but one X axon formed a single elongated patch. Y axons had thicker main branches (3-4 microns) than X axons (1.5-2.5 microns) at their point of entry to the cortex. The main axon trunks and their medium-calibre collaterals were myelinated, but the preterminal segments were unmyelinated and studded with boutons. Each X or Y axon contacted about seven to ten somata, but Y axons made more contacts per soma (three to six) than did X axons (two to three). In addition to somatic synapses, both X and Y axons formed asymmetric (type 1) synapses on dendritic spines and shafts, with spines forming the most frequent targets (80%). Each Y bouton made, on average, 1.64 synapses in area 17 and 1.79 synapses in area 18, whereas each X bouton made only 1.27 synapses on average. Although there are proportionally fewer Y axons than X axons entering area 17, the Y axons provide as many synapses as the X axons because of their larger arbors and multisynaptic boutons.

Afferent Pathways↗
PubMed1985

Innervation of cat visual areas 17 and 18 by physiologically identified X- and Y- type thalamic afferents. II. Identification of postsynaptic targets by GABA immunocytochemistry and Golgi impregnation.

The precise location of physiologically identified specific afferent input on the different types of cell in the visual cortex and the identification of the neurotransmitters of these cells are essential to a better understanding of the first stage of cortical processing. A combination of anatomical, neurochemical, and physiological methods was used to identify the cortical neurones that receive synaptic input from X- and Y-type afferents, which are thought to originate from cells of the lateral geniculate nucleus. One method relied on chance contacts made between single physiologically characterised axons, which had been injected with horseradish peroxidase (HRP), and the processes of cells impregnated by the Golgi method. These experiments revealed that both X and Y axons formed synapses on the dendrites of spiny stellate cells in layer 4. Y axons in both areas 17 and 18 established multiple synaptic contacts on basal dendrites of layer 3 pyramidal cells. One X axon contacted the apical dendrite of a layer 5 pyramidal cell and one Y axon contacted the dendrite of a large cell with smooth dendrites in layer 3. The maximum number of synapses made between one axon and a single postsynaptic cell was eight, although in most cases it was only one. It was concluded that one axon only provides a small fraction of the geniculate afferent input to an individual cell. A second method revealed that the somata in layer 4 in synaptic contact with the HRP-filled axon terminals were GABA-immunoreactive, and therefore might be involved in inhibitory processes. From light microscopic data it was found that somata receiving contacts from X axons in area 17 were significantly smaller (average diameter 15 microns) than those contacted by the Y axons in areas 17 and 18 (average diameter 24 microns). Somatic contacts were extremely rare in layer 6. These data show that the X and Y afferents may activate separate subsets of inhibitory neurones.

Animals↗
PubMed1985

Synaptic connections of intracellularly filled clutch cells: a type of small basket cell in the visual cortex of the cat.

Light and electron microscopic quantitative analysis was carried out on a type of neuron intracellularly filled with horseradish peroxidase. Two cells were studied in area 17, one of which was injected intra-axonally, and its soma was not recovered. One cell was studied in area 18. The two somata were on the border of layers IVa/b; they were radially elongated and received synapses from numerous large boutons with round synaptic vesicles. The dendrites were smooth and remained largely in layer IV. The cells can be recognised on the basis of their axonal arbor, which was restricted to layer IV (90-95% of boutons) with minor projections to layers III, V, and VI. Many of the large, bulbous boutons contacted neuronal somata, short collaterals often forming "claw"-like configurations around cells. The name "clutch cell" is suggested to delineate this type of neuron from other aspiny multipolar cells. Computer-assisted reconstruction of the axon showed that in layer IV the axons occupied a rectangular area about 300 X 500 microns, elongated anteroposteriorly in area 17 and mediolaterally in area 18. The distributions of synaptic boutons and postsynaptic cells were patchy within this area. A total of 321 boutons were serially sectioned in area 17. The boutons formed type II synaptic contacts. The postsynaptic targets were somata (20-30%), dendritic shafts (35-50%), spines (30%), and rarely axon initial segments. Most of the postsynaptic somata tested were not immunoreactive for GABA and their fine structural features suggest that they are spiny stellate, star pyramidal, and pyramidal neurons. The characteristics of most of the postsynaptic dendrites and spines also suggest that they belong to these spiny neurons. A few of the postsynaptic dendrites and somata exhibited characteristics of cells with smooth dendrites and these somata were immunoreactive for GABA. It is suggested that clutch cells are inhibitory interneurons exerting their effect mainly on layer IV spiny neurons in an area localised perhaps to a single ocular dominance column. The specific laminar location of the axons of clutch cell also suggests that they may be associated with the afferent terminals of lateral geniculate nucleus cells, and could thus be responsible for generating some of the selective properties of neurons of the first stage of cortical processing.

Animals↗
PubMed1985

Receptive field properties of neurones in visual area 1 and visual area 2 in the baboon.

In order to compare the receptive field properties of cells in the striate area (visual area 1; V1), and the parastriate area (visual area 2; V2), we have recorded from 174 cells in V1 and 112 cells in V2 in five anaesthetized and paralysed baboons (Papio ursinus). The receptive fields were mapped to determine their type, size and position in the visual field, and the binocular interaction, if any. Moving and stationary optimally oriented bars were used to distinguish cells with single "on" or "off" subregions and those with more than one such subregion (S and A types) from those with overlapping "on" or "off" subregion (C and B types). The A types had larger receptive fields than S types and C types had larger receptive fields than B types, but as receptive fields increase in size with eccentricity in V1 and even more rapidly in V2, the distinction between large and small receptive fields has to be defined for the different ranges of eccentricity. In V1 there are more cells with non-oriented receptive fields than in V2. In V1 S cells are found in all cortical layers except layer 5. C cells are absent from layer 4C, but predominate in layer 5. There is a preference for horizontal and vertical orientations in S cells only. The transition in cell properties from V1 to V2 occurs in two stages. There is a strip extending from the V1-V2 border for up to 6 mm containing the representation of the visual field from -2 degrees ipsilateral to +2 degrees (contralateral) azimuth in which the cell type distribution resembles that of V1 more than that of V2. By contrast, in V2 from 2 to 10 degrees there are very few S cells, many more C cells and over three times as many cells driven only by binocular stimulation, as compared to V1.

Animals↗
PubMed1982

Treating monocularly deprived lambs with 4-aminopyridine produces rapid changes in ocular dominance only after short periods of deprivation.

Lambs of various ages (4-30 days) were monocularly deprived for periods ranging from 4 to 51 days after which they were prepared for conventional electrophysiological recording from the striate cortex. Sufficient units were sampled to obtain a representative ocular dominance (OD) histogram. A second sample of units was then obtained after the lambs had been given an i.v. dose of 4-aminopyridine (4-AP; 0.5-5.3 mg/kg) which increases synaptic transmission. For four out of five lambs in which the deprivation had been of 4-5 days duration there was a significant increase in responsiveness of the deprived eye to stimulation after the 4-AP had been given. By contrast, only one out of four lambs which had been deprived for 19-51 days showed a significant recovery after 4-AP treatment. The results suggest that during the initial stages of monocular deprivation the deprived eye remains connected to, but is less effective in driving, cortical cells. One explanation of the failure to reactivate the deprived eye after long periods of deprivation is that the deprived eye becomes anatomically disconnected from cortical cells.

4-Aminopyridine↗
PubMed1979

The development of the binocular depth cells in the secondary visual cortex of the lamb.

In most respects, the response properties of cells in the secondary visual cortex of the newborn lamb were indistinguishable from those in the adult. The cells were sharply selective to orientation; the orientation preferences were the same in each eye, and they varied systematically as the electrode penetrated the cortex. The receptive-field organization did not differ noticeably from that in adults, and complex, hypercomplex, and a few simple cells were all observed. The ocular dominance distribution was similar to that in the adult. Most importantly, binocular cells were found with disparate receptive fields even in newborn, visually inexperienced animals. As in the adult, the disparities were largely horizontal, and they appeared to be arranged in columns. Many of the cells responded preferentially to a binocular stimulus at a particular disparity setting (often approximately zero), but unlike those in the adult almost all the binocular cells in the newborn lamb would also respond monocularly, and the enhancement at the optimal disparity was less than in the adult. The full development of binocular selectivity took several weeks, and was blocked by binocular deprivation. We conclude that the basic wiring of stereoscopic mechanisms is innate, but the development of mature binocular interaction may depend on an adaptive process which makes use of the visual information received during binocular stimulation.

Aging↗
PubMed1979

(Ludwig Guttmann)

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Anniversaries and Special Events↗
PubMed1979

Reversal of amblyopia in lambs.

We have tried to reverse the effects of shutting one eye in lambs firstly by the use of the CAM stimulator for one hour and secondly by the administration of 4-aminopyridine. Of these 4-aminopyridine produces rather greater recovery than the CAM stimulator, provided the eye has not been closed for more than 15 to 20 days. After this time neither method produces any measurable improvement under our conditions.

Amblyopia↗