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A Burkhalter

Publications and source records attributed to A Burkhalter.

At least 37 records · Page 2Linked to original sources
PubMed1993

Visualization of dendritic morphology of cortical projection neurons by retrograde axonal tracing.

Currently there is no reliable retrograde tracing technique for visualization of dendritic morphologies of projection neurons. Here we describe a simple and efficient method that can be used to label neurons in Golgi-like fashion. The approach relies on activity-dependent uptake of tracer. For this purpose we inject the glutamate receptor agonist N-methyl-D,L-aspartic acid (NMDA) at the tracer injection site to massively stimulate neurons and to thereby promote uptake of biocytin or biotinylated dextran amine (BDA) by axon terminals. The results show that co-injections of NMDA/biocytin and NMDA/BDA into the extrastriate lateromedial area (LM) of rat visual cortex labels large numbers of neurons in area 17 in Golgi-like fashion. Similarly injections of the lateral geniculate nucleus (LGN) lead to Golgi-like labeling of corticogeniculate neurons in area 17. The distribution of labeled neurons is highly topographic. In addition the method allows excellent preservation of ultrastructure, indicating that this approach is useful for determining the organization of neuronal circuits within the central nervous system.

Animals↗
PubMed1993

Organization of long-range inhibitory connections with rat visual cortex.

We have studied the laminar organization of local long-range inhibitory connections within rat primary visual cortex (area 17) by combining retrograde tracing of nerve cell bodies with glutamic acid decarboxylase immunocytochemistry. While most inhibitory connections are confined to within 0.4 mm of the injection site, a subset of neurons at the layer 5/6 border provide long-range (> 1 mm) inhibitory connections within area 17. However, other cell layers that contain similar local long-range horizontal connections, that is, lower layer 2/3, upper layer 5, and lower layer 6 (Burkhalter and Charles, 1990), show a much more restricted distribution of inhibitory connections. This suggests that cells at the layer 5/6 border play a role in the direct inhibition of neurons at a distant point of the topographic map. Similar double labeling studies reveal long-range inhibitory connections between visual areas. Following injections of fluorescent tracers into area 17, in horizontal sections inhibitory connections can be identified that are up to 8 mm long, linking the extrastriate subdivisions 18a and 18b with striate cortex. Conversely, injections of fluorescent tracers into the cytoarchitectonic subdivision 18a reveal local long-range inhibitory connections within 18a, long-range inhibitory connections between 18a and the cytoarchitectonic subdivision 18b, and inhibitory forward connections from area 17 to 18a. These results suggest that the communication between different cortical areas can be influenced by direct inhibitory connections.

Animals↗
PubMed1993

Hierarchical organization of areas in rat visual cortex.

To test the hypothesis that areas within rat visual cortex are organized in a multilevel hierarchy, we have employed Phaseolus vulgaris leucoagglutinin as an anterograde axonal tracer to visualize the laminar patterns of connections between different cortical areas. For identification of cortical areas, we used a combination of markers that included callosal connections, the patterns of inputs and outputs to ipsilateral cortical and subcortical targets, and geographical location. Projections from area 17 to every identified extrastriate target area extend throughout all layers of cortex and include layer 4. Area LM (lateromedial), contained within the cytoarchitectonic subdivision 18a, projects to area 17, area AL (anterolateral), area RL (rostrolateral), multiple sites within the posterior complex (PX), the anterior complex (AX), the far lateral complex (FLX), the medial complex (MX), perirhinal, entorhinal, retrosplenial, and presubicular cortex. Each of the projections to extrastriate areas resembles those originating from area 17. Only the projection to area 17 differs, and terminates largely in layers outside of lamina 4. Such projections are designated as feedback (Coogan and Burkhalter, 1990). The projections of a second area, AL, of the cytoarchitectonic subdivision 18a are similar to those of LM: all terminate in layers 1-6, except the inputs to area 17, LM, and a site in FLX, which spare layer 4. The feedback projection to LM provides further support that LM and AL constitute distinct cortical areas. Projections from additional distinct sites within area 18a that are located immediately lateral to LM and AL and are designated FLX make feedback projections to area 17 and projections involving all layers to LM and AL. Thus, unlike the asymmetrical laminar organization of reciprocal connections between area 17 and LM, 17 and AL, and LM and AL, the connections between LM and at least one site in FLX are symmetrical. Projections that include layer 4 can, therefore, be components of connections between different hierarchical levels as well as components of connections on the same hierarchical level. The MX sites contained within the cytoarchitectonic subdivision 18b send feedback projections to striate cortex, LM, AL, and PX within 18a. Thus, the connections between these areas are reciprocal and the laminar organization is asymmetrical. The projections to FLX include layer 4, and the projections to frontal, cingulate, and retrosplenial cortex resemble forward projections. Although the areal organization of extrastriate cortex is not yet fully resolved, using the patterns of intracortical connections we are able to construct a provisional hierarchy of cortical areas.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Differential expression of hyperpolarization-activated currents reveals distinct classes of visual cortical projection neurons.

Combining in vivo retrograde labeling and in vitro electrophysiological recording techniques, we examined the distributions, densities, and biophysical properties of hyperpolarization-activated inward currents in two types of isolated, identified visual cortical projection neurons, superior colliculus-projecting (SCP) and callosal-projecting (CP) cells. In SCP cells, two kinetically distinct time-dependent hyperpolarization-activated inward current components are present. We have termed these Ih,f and Ih,s to denote the fast and slow components, respectively, of Ih activation. In CP cells, in contrast, Ih,f and Ih,s are differentially expressed. In 59% of the CP cells examined, for example, both Ih,f and Ih,s were present. The properties of the currents are indistinguishable from those recorded from SCP cells, although both Ih,f and Ih,s are expressed at significantly lower densities in this subset of CP cells (as compared to the current densities in SCP cells). Of the remaining 41% of the CP cells studied, 26% were found to express only Ih,s, and 12% of the cells expressed neither Ih,f nor Ih,s. Taken together, these results reveal that the electrical properties of CP visual cortical neurons are considerably more heterogeneous than those of SCP cells. The differential expression of Ih,f and Ih,s is expected to influence the integrated responses of different types of cortical projection neurons to excitatory and inhibitory synaptic inputs.

Animals↗
PubMed1993

Development of local circuits in human visual cortex.

How we see the world largely depends on the organization of neuronal circuits in visual cortex. Physiological recordings in mammals indicate that circuits develop over a period that extends well into early postnatal ages (LeVay et al., 1980; Albus and Wolf, 1984). Our understanding of how these circuits are assembled during development is still fragmentary (Katz and Callaway, 1992). Here we describe the development of local connections within visual cortex, using the fluorescent dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate to trace axonal projections in post-mortem human brains. Vertical (intracolumnar) connections between layers 2/3 and 5, which link neurons representing the same point in the visual field, develop prenatally at 26-29 weeks gestation. In contrast, horizontal (intercolumnar) connections between different points in the visual field develop later. They first emerge prenatally at approximately 37 weeks gestation within layers 4B and 5. After birth (> 40 weeks gestation) the fiber density increases rapidly, showing a uniform plexus of connections at 7 weeks postnatal. The more adult-like patchiness of the projection, however, emerges after 8 weeks postnatal. Long-range horizontal connections within layer 2/3 develop after the connections within layers 4B, 5, and 6. These connections emerge after 16 weeks postnatal, long after cytochrome oxidase blobs have developed, and reach mature from sometime before 15 months of age. Unlike the patchy horizontal projections within layers 4B and 5, which seem to develop through a process of collateral elimination, long-range projections within layer 2/3 are patchy from the outset and seem to develop with greater topographical precision. The finding that intracolumnar connections develop before intercolumnar projections suggests that circuits that process local features of a visual scene develop before circuits necessary to integrate these features into a continuous and coherent neural representation of an image. In addition, the sequential development of horizontal connections within layer 4B before those within layer 2/3 suggests that circuits that may be related to the processing channel for visual motion develop in advance of those that may be more intimately related to the processing of form, color, and precise stereoscopic depth.

Aging↗
PubMed1992

Evidence for excitatory amino acid neurotransmitters in the geniculo-cortical pathway and local projections within rat primary visual cortex.

To examine the organization of axon collaterals of neurons that selectively take up and transport excitatory amino acids, we have used retrograde tracing with D-[3H]Aspartate after injections into different layers of rat primary visual cortex. The results show cells in the lateral geniculate nucleus retrogradely labeled from the cortex. Additional topographically precise input to the thalamic recipient layer 4 originates from neurons in the visual cortex lying in layers 2/3, 5 and 6. These inputs are reciprocated by point-to-point projections from layer 4. Layer 2/3 cells project to layers 5 and 6 in columnar fashion. Putative excitatory input to layer 2/3 originates from a vertical column of cells in layer 5 and the middle of layer 6. In addition layer 2/3 receives input via horizontal collaterals of topographically distant upper layer neurons, from more widespread projections in lower layer 6, and from very widespread projections of cells at the layer 5/6 border. Cells in the depth of layer 5 also distribute collaterals within layers 5 and 6. Our findings provide anatomical evidence that the geniculo-cortical pathway in the mammalian visual system may use excitatory amino acid transmitters. In addition, the results support the notion that most long range connections that link distant points of the topographic map are excitatory.

Animals↗
PubMed1991

Differential expression of voltage-gated calcium channels in identified visual cortical neurons.

Using the whole-cell patch-clamp technique, Ca2+ channel currents were examined in three distinct types of neurons derived from rat primary visual cortex. Callosal-projecting and superior colliculus-projecting neurons were identified following in vivo retrograde labeling with fluorescent "beads." A subset of intrinsic GABAergic visual cortical neurons was identified with the monoclonal antibody VC1.1. Although high voltage-activated Ca2+ channel currents were measured in all three cell types, clear differences in the densities of these channels were observed. There were also marked variations in the relative amplitudes of the inactivating and noninactivating components of the high voltage-activated currents, suggesting that N- and L-type Ca2+ channels are differentially distributed. Although low voltage-activated or T-type currents were measured in subsets of both types of projection neurons, they were not observed in VC1.1-positive cells. These results provide a direct demonstration that voltage-gated Ca2+ channels are expressed in neurons of the mammalian visual cortex and reveal that the distribution and densities of different Ca2+ channel types in diverse classes of visual cortical neurons are distinct.

Animals↗
PubMed1990

Organization of local axon collaterals of efferent projection neurons in rat visual cortex.

We have studied the laminar origins of local long-range connections within rat primary visual cortex (area 17), by using retrograde tracing of nerve cell bodies with fluorescent markers. Injections throughout the thickness of cortex produce distinct laminar labeling patterns which indicate that a substantial number of cells in layers 2/3, 5, and 6 have wide local axon collateral arbors, while the local arbors of layer 4 cells are much narrower. Double labeling experiments which combined area 17 injections with injections into different projection targets of area 17 (opposite area 17, area 18a, and area 18b) show that many cortico-cortically projecting cells make widespread projections within area 17. In contrast, the overwhelming majority of subcortically projecting cells have narrow collateral arbors within area 17. Anterograde tracing of local projections within areas 17 with the lectin Phaseolus vulgaris leucoagglutinin shows an extensive system of horizontally running fibers which terminate in distinct 0.15-0.25 mm wide clusters up to 1.8 mm from the injection site. On horizontal sections the termination pattern resembles a closely spaced lattice. The results indicate that cortico-cortically projecting cells provide for long-range interactions between distant points of the visuotopic map, while subcortically projecting cells mediate information within a cortical column. Interestingly, subcortically projecting cells differ functionally from cortico-cortically projecting cells in that they are not orientation selective (Klein et al., Neurosci. 17:57-78, '86; Mangini and Pearlman, J. Comp. Neurol. 193:203-222, '80; Simmons and Pearlman, J. Neurophysiol. 50:838-848, '83). We therefore suggest that cortico-cortically projecting cells with wide collateral arbors are orientation selective and that clustered long-range projections within area 17 connect columns with similar functional specificity.

Animals↗
PubMed1990

Conserved patterns of cortico-cortical connections define areal hierarchy in rat visual cortex.

The prevalence of reciprocal connections in the cerebral cortex indicates that they play a fundamental role in the processing of sensory information. We have investigated the laminar termination patterns of such paired connections between different visual cortical areas of the rat, and have found two basic projection types: one which includes layer 4 and a second which includes layer 1 and avoids layer 4. The projections from primary visual cortex (area 17) to extrastriate visual cortical targets in the cytoarchitectonical areas 18a and 18b, and from 18a to a site in 18b, are of the first type. In contrast, the return projections from 18a and 18b to area 17 and from 18b to 18a, are of the second type. Thus each pair of connections has one element of each type, giving every circuit a nearly identical asymmetric structure. These laminar patterns resemble those of forward and feedback connections in primate cortex, indicating that corticocortical connectivity patterns are highly conserved through evolution, and that, as in monkeys, these connections define a hierarchical organization of areas in rat visual cortex.

Animals↗
PubMed1989

Intrinsic connections of rat primary visual cortex: laminar organization of axonal projections.

The organization of local projections within the rat primary visual cortex (area 17) was investigated by tracing fibers with HRP in in vitro brain slices. The projections from different layers showed distinct laminar patterns. Layer 4 made a strong, topographically precise, projection to lower layer 2/3; weaker projections extended laterally and terminated diffusely in layer 2/3 but also ran vertically to layers 5 and 6. The connections of lower and upper layer 2/3 were reciprocal and point-to-point. Within layer 2/3, a large number of fibers ran horizontally and terminated at variable distances from the injection site without making terminal clusters. The main output from layer 2/3 was to layer 5. The most prominent projections from the upper half of layer 5 were to layers 2/3 and 6; lower layer 5, in contrast, made wide-ranging, clustered projections to layer 1, the bottom of layer 2/3, and the top of layers 4 and 5. The patches were 130-160 micron wide and spaced apart by 230-260 micron. The main projection that arose from the superficial layer 6 terminated in layer 4 above the injection site. In contrast, lower layer 6 made clustered projections to the layer 3/4 border, extending up to 2 mm in the coronal plane. The patches were 190-220 micron wide and spaced apart by 320-390 micron. Additional projections went to the layer 5/6 border and layers 1 and 2. These results indicate that geniculocortical input is processed through interlaminar connections that are topographically precise, widespread, or patchy. These connectivity patterns suggest a role for these connections in the transformation of functional maps between layers; focused projections preserve the architecture of the layers of origin, and diverging or patchy projections rearrange this organization and form new maps in the target layers (Lund: Annu. Rev. Neurosci. 11:253-288, '88). However, only a few interlaminar connections show one of these patterns in isolation, making it difficult to assign a single function to a particular connection. We, therefore, tentatively conclude that projections terminating in layers 1-4, with the possible exception of the connection between upper layer 6 and layer 4, transform functional maps. In contrast, the topographically precise projections from upper to lower layers preserve functional maps. The specific role of these connections in the construction of receptive field properties, however, is not known.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Organization of corticocortical connections in human visual cortex.

Clinical and psychophysical observations indicate that the visual cortex is critical for the perception of color, form, depth, and movement. Little, however, is known about the cortical circuitry that underlies these functions in humans. In an attempt to learn more about these connections, we have traced projections of primary (V1) and secondary (V2) visual cortex in the postmortem, fixed human brain, using the fluorescent dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate as an axonal marker. The results show that V1 makes a forward projection to layers 3 and 4 of V2, and V2 projects back to layers 1, 2, 3, 5, and 6 of V1. Some V2 injections also show an input to layer 4B of V1. Projections to 4B probably originate from cytochrome oxidase (CO)-reactive stripes that we have identified in V2. Differential connections between CO-rich (blobs) and CO-poor regions (interblobs) also exist within V1; blobs are connected to blobs and interblobs are connected to interblobs. The results show that the connections in human visual cortex are similar to those of nonhuman primates and that their organization is consistent with the concept of multiple processing streams in the visual system.

Adult↗
PubMed1988

Sequential development of connections between striate and extrastriate visual cortical areas in the rat.

In these experiments we have asked whether the projection from the rat's primary visual cortex, area 17, to the extrastriate visual cortical area 18a is formed in a sequence and whether that sequence resembles the pattern of inside-out cortical neurogenesis. For this purpose fluorescent retrograde tracers were injected into area 18a at different postnatal ages (P1, P5, adult). Animals survived until 3-4 weeks of age, after migration is complete and neurons have arrived at their final laminar location. In the ipsilateral cortex, P1 injections retrogradely labeled cells in layers 5 and 6 of area 17. Labeling after P5 injections extended into more superficial layers and included the bottom of layer 2/3 and layers 4-6. After P5, more labeled cells were found at the top of layer 2/3, producing the adult laminar pattern, where the projection originates predominantly from layer 2/3. A similar sequence of laminar labeling was observed in the transcallosal connection of area 18a. This sequence of labeling, deep layers before superficial, resembles the pattern in which cortical neurons are born and indicates that axons arrive at their cortical targets in the order the cells were generated.

Animals↗
PubMed1987

Recent investigations of mechanisms of chemically induced skin irritation in laboratory mice.

The time course, dose response, components of inflammation, and involvement of putative mediators of inflammation in irritation induced by different chemicals was compared using a mouse ear swelling technique. Differences in time courses of inflammation produced by the irritants were not solely due to differences in rates of penetration. Changes in blood flow and permeability of vessels were phasic with different numbers of phases induced by different irritants. Effects of antagonist, synthesis, inhibitors, and depleting agents of putative inflammatory mediators on intensity of inflammation varied for different irritants. These studies demonstrate that all chemicals do not produce skin irritation by a common inflammatory pathway.

Alkynes↗
PubMed1987

Nonenzymatic glycation of immunoglobulins does not impair antigen-antibody binding.

We glycated immunoglobulins from commercial kits designed to measure human ferritin, thyrotropin, and transferrin, and compared the calibration curves for assays utilizing glycated antibodies with those of assays utilizing non-glycated antibodies. Glycation was verified by borate affinity chromatography and assay with thiobarbituric acid reagent. We found no evidence that antigen-antibody binding is impaired by nonenzymatic glycation of antibodies. Our results provide no evidence in support of the supposition that glycation may be a contributory factor in the decreased resistance of diabetics to infection.

Antibodies↗
PubMed1986

Anatomical and physiological asymmetries related to visual areas V3 and VP in macaque extrastriate cortex.

This report provides an overview of the functional organization of cortex immediately anterior to area V2 in extrastriate visual cortex of the macaque monkey. Contrary to previous suggestions that a single area, V3, lies anterior to V2, we have obtained evidence that this strip of cortex includes two separate areas, V3 and the ventral posterior area, VP. The evidence supporting this conclusion is based on dorso-ventral asymmetries in cortico-cortical connections, myeloarchitecture, and single-unit physiological properties relating to the processing of information about color and motion.

Action Potentials↗
PubMed1986

Processing of color, form and disparity information in visual areas VP and V2 of ventral extrastriate cortex in the macaque monkey.

The responses of single cells to light bars of different orientation, direction of motion, speed, binocular disparity, and wavelength were systematically analyzed in areas V2 and VP of ventral extrastriate visual cortex in the macaque monkey. Selectivity for each of these parameters was assessed quantitatively using computer-controlled procedures. In both VP and V2 (both representing the superior contralateral quadrant), more than half of the cells studied were selective for stimulus color and more than half for stimulus orientation. In contrast, only a small minority of the VP and V2 cells were selective for the direction of stimulus motion. Comparison with reports of single-unit properties in dorsal extrastriate cortex suggests there are no major differences in the incidence of orientation, direction, and color selectivity between ventral and dorsal subdivisions of V2. Between V3 and VP, though, there are marked differences: Color-selective cells are much less common in V3 than VP, whereas direction-selective cells are more common in V3. This dorsoventral difference in the distribution of neuronal response properties suggests a significant asymmetry in the way visual information is processed in upper and lower parts of the visual field. The properties of cells in VP suggest that it plays an important role in both form and color vision, similar to that attributed to area V4.

Animals↗
PubMed1985

Mechanisms of chemically induced skin irritation. I. Studies of time course, dose response, and components of inflammation in the laboratory mouse.

The possibility that chemicals induce skin irritation by multiple mechanisms was studied in laboratory mice. The time course and dose response to topical application of phenol, croton oil, benzalkonium chloride, ethyl phenylpropiolate (EPP), and methyl salicylate were compared. The responses to each chemical were measured as changes in ear thickness following application to one ear. Maximal responses were as follows: methyl salicylate 20 min, phenol 1 hr, croton oil and benzalkonium chloride 6 hr, and EPP 8 hr. The response to EPP included an early, smaller response at 1 hr. Time courses of the responses were not altered by changing the vehicle in which the irritants were applied or by altering the dose. The rates of regression of the inflammatory responses also varied. Although visibly normal, thickness of ears treated with either phenol or benzalkonium chloride remained 0.05 to 1 mm thicker than solvent-treated control ears for 6 weeks. Although the incidence of prolonged thickness was dose related, it was not determined by the intensity of the acute response; doses of other irritants which produced equivalent acute increases in ear thickness did not produce similar changes. The components of the acute responses, i.e., vascular permeability, change in blood flow, and cellular infiltration, to 5 mg methyl salicylate, 2 mg EPP, and 0.05 mg croton oil were compared in studies of tissue histology, changes in vascular permeability by trypan blue and 125I-labeled bovine serum albumin, and change in local surface temperature as an index of blood flow. The histology of the reactions at the time of maximum response to the chemicals differed. Multiple periods of increased permeability and increased surface temperature were produced by the irritants. The permeability and blood flow responses produced by the irritants varied in number, time of occurrence relative to time of application and to time of maximum response, and in magnitude of the changes. Differences in time courses of the responses which were not altered by experimentally varying rate of absorption and in components of the inflammatory response to the three irritants suggest that chemicals induce skin irritation by multiple mechanisms.

Absorption↗