PubMed Health⌕ Search

Biomedical subjects

M Sur

Publications and source records attributed to M Sur.

At least 73 records · Page 4Linked to original sources
PubMed1993

Visual projections induced into the auditory pathway of ferrets: II. Corticocortical connections of primary auditory cortex.

Although the development of corticocortical projections has been well studied, less is known about the role of sensory inputs in the specification of these connections. As part of an ongoing series of studies in our laboratory, we have examined the role of thalamic input modality in the development of corticocortical connections. These studies involve making unilateral lesions and inducing retinal inputs into the auditory thalamus (MGN) during early development in ferrets, thereby conferring visual responsiveness on primary auditory cortex (AI). In this way we can examine the role of input identity in cortical specification in general, and connectivity patterns specifically. A previous paper (Pallas et al. [1990] J. Comp. Neurol. 298:50-68) described the pattern of thalamocortical and corticothalamic connections of auditory cortex in normal and lesioned animals. This study compares the pattern of auditory corticocortical connections in normal and lesioned animals. We injected neuroanatomical tracers into AI and mapped out the distribution of retrogradely labelled cells in the cortex. We report that the cortical inputs to ferret AI resembled those in cats, and that the pattern of ipsi- and contralateral corticocortical connections of ferret AI with visual input was similar to the normal pattern. Auditory cortex with visual input did not make ectopic connections with visual cortex, but maintained its connections with other auditory cortical areas. These results suggest that the overall corticocortical connections of an area are not influenced by the modality or activity pattern of its inputs. In particular, altering the input activity to a cortical area does not seem to promote the formation of entirely new connections, although small changes in the strength of existing connections are possible (Sur et al. [1990] Trends Neurosci. 13:227-233).

Animals↗
PubMed1993

Experimentally induced visual projections to the auditory thalamus in ferrets: evidence for a W cell pathway.

We have previously reported that following specific neonatal brain lesions in ferrets, a retinal projection is induced into the auditory thalamus (Sur et al., Science 242:1437, '88). In these "rewired" ferrets, a novel visual pathway is established through auditory thalamus [the medial geniculate nucleus (MGN)] and primary auditory cortex (A1); cells in both MGN and A1 are visually responsive and exhibit properties similar to those of visual cells in the normal visual pathway. In this paper, we use three approaches--physiological, anatomical, and developmental--to examine which of the retinal ganglion cells project to the MGN in these rewired ferrets. We find that: 1) physiological response properties of postsynaptic visual cells in the MGN are W-like; 2) retinal ganglion cells back-filled from the MGN are small and similar to soma sizes of subsets of the normal retinal W cell population; and 3) subpopulations of these small cells can be preferentially rerouted to the MGN in response to different surgical manipulations at birth, consistent with differential W cell projection patterns in normal animals. These data suggest that retinal W cells come to project to the MGN in rewired animals. These findings not only provide a basis on which to interpret functional properties of this novel visual pathway, but also provide important information about the developmental capabilities of specific retinal ganglion cell classes and the regulation of their projections by target structures in the brain during development.

Animals↗
PubMed1993

Spike trains and signaling modes of neurons in the ferret lateral geniculate nucleus.

Intracellular recordings were used to examine the action potential firing modes of cells in the ferret lateral geniculate nucleus (LGN) in vitro. We compared the effects of altered membrane voltage on patterns of action potential trains evoked by direct current injection and by retinal afferent (synaptic) stimulation. The results confirm that LGN cells in the ferret can fire action potentials in the "burst" and "tonic" modes that have been described previously for other species. At depolarized membrane potentials, LGN neurons respond to sustained depolarization with short-latency trains of action potentials whose frequency is directly proportional to the amount of current injected. At hyperpolarized membrane potentials, LGN cells enter burst mode, in which depolarizing inputs are differentiated into brief high-frequency discharges whose latency varies with membrane potential. We also observed a "mixed" mode, in which LGN cell responses to synaptic or injected currents within a narrow range of membrane potentials reflect aspects of both burst and tonic firing simultaneously. Thus a striking consequence of the interplay among voltage-dependent membrane conductances in thalamic cells is wide variability in length, duration, and latency of spike discharges elicited by identical stimuli. These results also suggest that the concept that LGN cells display only two active response modes must be expanded to include varying amounts of delay and the possibility of mixed discharges.

Action Potentials↗
PubMed1993

Cortical specification: microcircuits, perceptual identity, and an overall perspective.

The microcircuitry within a cortical area and its perceptual identity are both specified relatively late in development. We have asked whether and how the pattern of input activity during development influences these features of cortex. Routing visual projections to the auditory pathway in ferrets leads to visual activation of the developing auditory cortex, causing auditory cortex to receive patterns of input activity very different from normal. Visual inputs respecify, in instructive fashion, the microcircuitry within primary auditory cortex and alter the perceptual identity of the area so that its activation is identified with visual stimuli. Several other features of primary auditory cortex remain unaltered, however, by the change in input modality. In general, the pattern of input activity is one of several environmental cues that influence the developing cortex and interact with its intrinsic developmental program. It is clear from our (as well as other) experiments that appropriate environmental signals must be present at the appropriate time in development in order to influence cortical specification.

Acoustic Stimulation↗
PubMed1992

The effects of selective glutamate receptor antagonists on synchronized firing bursts in layer III of rat visual cortex.

In the rat visual cortex in vitro, single-shock stimulations applied to the border between layer VI and the white matter evoke synchronized burst-firing by units in layer III. We have examined the effects of glutamate receptor antagonists on this activity, with antagonists applied via the bath to allow correlation of effects with concentrations. All synaptically driven components (recorded extracellularly as field potential 'S2' spikes, dipoles 'W1' and 'W2', and coinciding single-unit spikes) were inhibited by greater than 90% in 1.0 mM kynurenic acid and in 3 or 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, which selectively blocks AMPA/kainate receptors). S2 spike amplitudes were reduced by half in 0.7 microM CNQX. 2-Amino-5-phosphonovalerate (APV), a specific blocker of NMDA receptors, did not prevent S2 spike burst or horizontal spread of bursting within layer III. However, APV reduced the duration of synchronized bursts and the slower potentials which followed. In Mg(2+)-free medium, new components appeared which were APV-sensitive: (1) low amplitude spikes, distributed spatially like S2 spike, but recurring more slowly, and (2) slow potentials, distributed spatially like W1 and W2 potentials, but lasting for hundreds of milliseconds. The amplitudes of these spikes were reduced by half in 3 microM D-APV. Our data imply that: (1) glutamate receptors play a major role in mediating local, excitatory neurotransmission in the supragranular layers of neocortex, with NMDA and AMPA/kainate subtypes each subserving somewhat different functions; (2) AMPA/kainate receptors mediate rapid excitatory transmission between layer III neurons, responsible for driving the first 15 ms of synchronized bursts; (3) currents gated by NMDA receptors determine the duration of coherent firing bursts, and drive asynchronous neuronal firing following bursts; and (4) under conditions which circumvent block by extracellular Mg2+, activation of NMDA receptors greatly enhances and prolongs the response to single-shock stimulations. In vivo, activation of layer III neurons is likely to depend significantly upon currents gated by NMDA receptors whenever repetitively firing excitatory inputs summed over several tens of milliseconds provide enough depolarization to lift block by extracellular Mg2+.

2-Amino-5-phosphonovalerate↗
PubMed1992

Membrane and synaptic properties of developing lateral geniculate nucleus neurons during retinogeniculate axon segregation.

During the first postnatal month in the ferret (Mustela putorius furo), the projections from the retina to the lateral geniculate nucleus (LGN) become segregated into eye-specific layers and ON and OFF sublayers, a process that is thought to depend in part on neuronal activity. Remarkably, virtually nothing is known about the physiological features of LGN neurons during this period. We have recorded intracellularly from 46 A-layer neurons in slices of the ferret LGN between the ages of postnatal days 7 and 33. The passive membrane properties and current-voltage relationships of the developing neurons were similar in many, though not all, respects to those of adult LGN neurons. Action potentials in younger animals were smaller in amplitude and longer in duration than in older animals, but cells at all ages were capable of producing spike trains whose latency and spike number varied with stimulus intensity. In addition, cells at all ages responded with low-threshold potentials upon release from hyperpolarization. Slightly more than half of the LGN neurons responded to optic tract stimulation with excitatory postsynaptic potentials (EPSPs), inhibitory postsynaptic potentials (IPSPs), or EPSP-IPSP pairs, beginning with the youngest ages. Thus, as early as the second postnatal week, and much before the onset of pattern vision, LGN neurons have many of the membrane and synaptic properties of adult thalamic neurons. These data are consistent with LGN cells playing a significant role in activity-dependent reshaping of the retinogeniculate pathway.

Action Potentials↗
PubMed1992

NMDA receptors in sensory information processing.

During the past year electrophysiological studies, particularly in the visual and somatosensory systems, have begun to uncover the specific roles played by NMDA receptors in the processing of sensory information. Many of the features of NMDA-receptor-mediated sensory responses reflect known properties of the receptor.

Afferent Pathways↗
PubMed1992

Retinogeniculate EPSPs recorded intracellularly in the ferret lateral geniculate nucleus in vitro: role of NMDA receptors.

We used an in vitro preparation of the ferret lateral geniculate nucleus (LGN) to examine the role of the NMDA class of excitatory amino acid (EAA) receptors in retinogeniculate transmission. Intracellular recordings revealed that blockade of NMDA receptors both shortened the time course and reduced the amplitude of fast and slow components of excitatory postsynaptic potentials (EPSPs) evoked by optic tract stimulation. The amplitude and width of the EPSPs mediated by NMDA receptors increased as membrane potential was depolarized towards spike threshold. Individual LGN cells were influenced to varying extents by blockade of NMDA receptors; NMDA and non-NMDA receptor blockade together attenuated severely the entire retinogeniculate EPSP. The dependence of all components of retinogeniculate EPSPs (and action potentials) on NMDA receptor activation supports the hypothesis that the NMDA receptor participates in fast (less than 10 ms) synaptic events underlying conventional retinogeniculate transmission. The voltage dependence of the NMDA receptor-gated conductance suggests strongly that the transmission of retinal information through the LGN is subject to modulation by extraretinal inputs that affect the membrane potential of LGN neurons.

2-Amino-5-phosphonovalerate↗
PubMed1992

Effect of stimulus contrast and size on NMDA receptor activity in cat lateral geniculate nucleus.

1. We studied the effect of varying excitatory and inhibitory drive on the N-methyl-D-aspartate (NMDA) receptor-mediated component of the visual responses of neurons in the cat dorsal lateral geniculate nucleus (dLGN) by varying the contrast and size of stimuli presented to the receptive fields of these cells. 2. Cells were classified as either on- or off-center, X or Y, and lagged or nonlagged. Stimulus contrast, and hence the amount of excitatory drive, was varied by changing the brightness of a spot, whose size and location matched the cell's receptive field center, relative to a fixed background luminance. Responses to varying contrast were collected from each cell before, during, and after iontophoretic application of D-2-amino-5-phosphonovaleric acid (D-APV), a specific NMDA receptor antagonist. From each contrast-response plot, a sigmoidal curve fit yielded five parameters on which we examined the effect of D-APV: the threshold contrast, saturation contrast, contrast at half saturation (C50), slope (gain) at C50, and saturation response. 3. In most cells, application of D-APV reduced both the saturation response and the gain of the contrast-response curve, but did not reduce or change significantly the threshold contrast, saturation contrast, or C50. 4. Cells varied in their sensitivity to D-APV, but for any given cell, the D-APV-sensitive component was nearly always a linear function of the control visual response level. Thus, for a spot of optimal size, there was a constant proportion of the visual response attributable to NMDA receptors, regardless of the amplitude of the response. 5. When the effect of D-APV on the visual responses to an optimal spot at varying contrasts was compared among different classes of dLGN cells, the visual responses of lagged X cells were reduced to a greater extent than those of either nonlagged X cells or the combined population of nonlagged X and Y cells. 6. Stimulus size (spot diameter) was also varied systematically at a fixed contrast to vary the inhibitory drive to dLGN cells. As stimulus size was increased, the response first increased because of increased stimulation of the receptive field center and then decreased because of increasing amounts of surround inhibition. 7. The D-APV-sensitive component of individual cell responses was greater when the stimulus spot was less than or equal to optimal size than when the spot was larger. Thus the contribution of NMDA receptors to the visual response decreased with increasing surround inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1992

Visual projections routed to the auditory pathway in ferrets: receptive fields of visual neurons in primary auditory cortex.

How does cortex that normally processes inputs from one sensory modality respond when provided with input from a different modality? We have addressed such a question with an experimental preparation in which retinal input is routed to the auditory pathway in ferrets. Following neonatal surgical manipulations, a specific population of retinal ganglion cells is induced to innervate the auditory thalamus and provides visual input to cells in auditory cortex (Sur et al., 1988). We have now examined in detail the visual response properties of single cells in primary auditory cortex (A1) of these rewired animals and compared the responses to those in primary visual cortex (V1) of normal animals. Cells in A1 of rewired animals differed from cells in normal V1: they exhibited larger receptive field sizes and poorer visual responsivity, and responded with longer latencies to electrical stimulation of their inputs. However, striking similarities were also found. Like cells in normal V1, A1 cells in rewired animals exhibited orientation and direction selectivity and had simple and complex receptive field organizations. Furthermore, the degree of orientation and directional selectivity as well as the proportions of simple, complex, and nonoriented cells found in A1 and V1 were very similar. These results have significant implications for possible commonalities in intracortical processing circuits between sensory cortices, and for the role of inputs in specifying intracortical circuitry.

Animals↗
PubMed1991

Disruption of retinogeniculate afferent segregation by antagonists to NMDA receptors.

Afferent activity has an important role in the formation of connections in the developing mammalian visual system. But the extent to which the activity of target neurons shapes patterns of afferent termination and synaptic contact is not known. In the ferret's visual pathway, retinal ganglion cell axons from each eye segregate early in development into eye-specific laminae in the lateral geniculate nucleus (LGN). The dorsal laminae (termed laminae A and A1) then segregate further into inner and outer sublaminae that retain input from on-centre and off-centre retinal axons, respectively. Thus, individual retinogeniculate axons form terminal arbors within laminae A and A1 that are restricted to one inner or outer sublamina. We report here that blockade of N-methyl-D-aspartate (NMDA) receptors on LGN cells with specific antagonists during the period of sublamina formation prevents retinal afferents from segregating into 'On' and 'Off' sublaminae. Retinogeniculate axons have arbors that are not restricted appropriately, or are restricted in size but inappropriately positioned within the eye-specific laminae. NMDA receptor antagonists may specifically disrupt a mechanism by which LGN neurons detect correlated afferent and target activity, and have been shown to reduce retinogeniculate transmission more generally, causing LGN cells to have markedly reduced levels of activity. These results therefore indicate that the activity of postsynaptic cells can significantly influence the patterning of inputs and the structure of presynaptic afferents during development.

2-Amino-5-phosphonovalerate↗
PubMed1991

NMDA and non-NMDA receptors mediate visual responses of neurons in the cat's lateral geniculate nucleus.

1. We have examined the effects of iontophoresing specific antagonists to excitatory amino acid receptors on the visual responses of cells in lamina A or A1 of the cat's lateral geniculate nucleus (LGN). 2. Cells were classified as On- or Off-center, X or Y, and lagged or nonlagged. The effects of antagonists were studied while cells were stimulated with spots of the appropriate contrast covering the receptive-field center. 3. The N-methyl-D-aspartate (NMDA) receptor antagonists D-2-amino-5-phosphonovaleric acid (D-APV) and 3-(+/-)-2-carboxypiperazin-4-yl)- propyl-1-phosphonic acid (CPP), when iontophoresed at doses that specifically antagonized NMDA-induced responses but not kainate-induced responses, reduced the responses of all cell types in the LGN, including X and Y cells, lagged and nonlagged cells, and On- and Off-center cells. 4. The non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), when applied at doses that specifically antagonized kainate-induced responses but not NMDA-induced responses, also reduced the visual responses of each of the cell types in the LGN. 5. We analyzed quantitatively the effects of D-APV and CNQX on LGN cells. D-APV reduced the responses of lagged cells to a greater extent than the responses of nonlagged cells. CNQX reduced the responses of lagged and nonlagged cells to a similar extent. There was no difference in the effect of D-APV or of CNQX on X and Y cells or on On- and Off-center cells. 6. We analyzed the effects of the antagonists on separate components of responses, including an early component comprising the first 100 ms of response and a late component comprising the next 300 ms of response. D-APV reduced the late component of lagged cell responses to a greater extent than either the early component of the same cells or the early or late component of nonlagged cells. CNQX had nearly equivalent effects on both response components of all cell types. 7. These data indicate that NMDA and non-NMDA receptors make similar contributions to the responses of On- and Off-center and X and Y cells in the LGN. Lagged and nonlagged cells are not differentiated with respect to the contribution of non-NMDA receptors to their visual responses. The greater contribution of NMDA receptors to the responses of lagged cells is consistent with the large contribution made by these receptors to the late response components of lagged cells.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1990

A map of visual space induced in primary auditory cortex.

Maps of sensory surfaces are a fundamental feature of sensory cortical areas of the brain. The relative roles of afferents and targets in forming neocortical maps in higher mammals can be examined in ferrets in which retinal inputs are directed into the auditory pathway. In these animals, the primary auditory cortex contains a systematic representation of the retina (and of visual space) rather than a representation of the cochlea (and of sound frequency). A representation of a two-dimensional sensory epithelium, the retina, in cortex that normally represents a one-dimensional epithelium, the cochlea, suggests that the same cortical area can support different types of maps. Topography in the visual map arises both from thalamocortical projections that are characteristic of the auditory pathway and from patterns of retinal activity that provide the input to the map.

Animals↗
PubMed1990

Monoclonal antibody Cat-301 identifies Y-cells in the dorsal lateral geniculate nucleus of the cat.

In mammalian visual pathways, information is carried in parallel channels from the retina through the visual thalamus to visual cortex. The cat's visual pathway comprises at least three major channels that begin with the X, Y, and W ganglion cells in the retina. In the dorsal lateral geniculate nucleus (LGN) of the thalamus, neurons in the X, Y, and W channels receive input from their retinal counterparts and can be discriminated from one another on the basis of their anatomical and physiological properties. The search for molecular properties that might correlate with anatomically or physiologically defined classes of neuron has been a major area of research in recent years. Monoclonal antibody Cat-301 recognizes a neuronal surface-associated proteoglycan in many areas of the mammalian central nervous system. In the cat LGN Cat-301 immunoreactivity is restricted to a subset of neurons. We show here that the distribution, size, morphology, and cortical projection pattern of Cat-301-positive LGN neurons match those previously described for Y-cells. Taken together with our previous studies of the development of immunoreactivity and the sensitivity of Cat-301 staining to visual deprivation, these studies suggest that Cat-301 specifically recognizes Y-cells in the cat LGN. These results indicate that neurons within a physiologically and anatomically defined cell class share a molecular property. They further suggest that differences in molecular traits may reflect, and possibly subserve, differences in anatomical and physiological characteristics.

Animals↗
PubMed1990

Visual projections induced into the auditory pathway of ferrets. I. Novel inputs to primary auditory cortex (AI) from the LP/pulvinar complex and the topography of the MGN-AI projection.

The organization of cortical circuitry responsible for processing sensory information is a subject of intense examination. However, it is not known whether cortical cells in different sensory cortices process information in a way that is specific to the modality of their input, or whether there are commonalities in processing circuitry across different cortices. In our laboratory, this question has been investigated at the level of the geniculocortical pathway by routing information of one sensory modality into the processing circuitry of another modality. Appropriate early lesions cause growth of retinal axons into the auditory thalamus (MGN) (Sur et al., Science 242:1437, '88). Previously, we have established that the MGN carries the resulting visual information on to primary auditory cortex (AI), which thus contains visually responsive neurons and a topographic representation of the retina (Roe et al., Soc. Neurosci. Abstr. 14:460, '88; Sur et al., Science 242:1437, '88). In this paper, we describe anomalous projections from the dorsal part of the thalamus, specifically the lateral posterior/pulvinar complex, into AI. This result demonstrates that thalamic neurons belonging to one modality can be induced to project to cortex that is normally of a different modality. In addition, we have studied in detail the nature of the MGN to AI projection in these animals as compared to the normal projection. The MGN to AI projection appears to be unaltered by the lesions; the location and topography of labelled cells are similar to that in normal animals. Because the MGN to AI projection is still highly divergent along the "isofrequency" dimension when compared to the tonotopic dimension, our data suggest that visual topography in the cortical map is created within the auditory cortex, perhaps by activity-dependent sharpening of the retinal representation during development.

Animals↗
PubMed1990

Morphology of single intracellularly stained axons terminating in area 3b of macaque monkeys.

We have studied the morphology of single thalamocortical axons innervating area 3b of postcentral somatosensory cortex in macaque monkeys. We recorded from axons in the white matter below the representation of the hand in postcentral cortex in two monkeys (Macaca fascicularis) by using micropipettes filled with horseradish peroxidase (HRP). When an axon was recorded, we delineated its receptive field and determined its modality, and if cutaneous, whether it was slowly or rapidly adapting (SA or RA). We then impaled the axon and injected it with HRP. We recorded and successfully injected many more RA than SA axons, possibly because of differences in their true proportions. The RA axonal arbors varied in mediolateral extent from 350 to 800 microns with a mean of 600 microns. One of the RA axons gave rise to four separate arbors spanning 2.5-3.0 mm of cortex. The single SA axon we recovered was 370 microns in width. We suggest that the individual terminal zones underlie the columnar parcellation of the somatosensory cortex. The presence of arbors spanning several such columns suggests that all regions within the arbor may not be equally effective in driving cortical cells under normal conditions, and such arbors may provide the substrate for a cortical response to alterations in the pattern of input.

Animals↗
PubMed1990

Cross-modal plasticity in cortical development: differentiation and specification of sensory neocortex.

Early developmental manipulations can induce sensory afferents of one modality to project to central targets of a different sensory modality. We and other investigators have used such cross-modal plasticity to examine the role of afferent inputs and their patterns of activity in the development of sensory neocortex. We suggest that the afferent rewiring can significantly influence the internal connectivity or microcircuitry of sensory cortex, aspects of which appear to be determined or specified relatively late in development, but that they cannot influence, or influence only to a minor extent, the laminar characteristics and external connectivity patterns of cortex, which appear to be specified earlier.

Animals↗