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L C Katz

Publications and source records attributed to L C Katz.

At least 37 records · Page 2Linked to original sources
PubMed1997

Opposing roles for endogenous BDNF and NT-3 in regulating cortical dendritic growth.

Neurons within each layer of cerebral cortex express multiple members of the neurotrophin family and their corresponding receptors. This multiplicity could provide functional redundancy; alternatively, different neurotrophins may direct distinct aspects of cortical neuronal growth and differentiation. By neutralizing endogenous neurotrophins in organotypic slices of developing cortex with Trk receptor bodies (Trk-IgGs), we found that BDNF and NT-3 oppose one another in regulating the dendritic growth of pyramidal neurons. In layer 4, both endogenous and exogenous NT-3 inhibited the dendritic growth stimulated by BDNF. In contrast, in layer 6 both endogenous and exogenous BDNF inhibited dendritic growth stimulated by NT-3. These antagonistic actions of endogenous BDNF and NT-3 provide a mechanism by which dendritic growth and retraction can be dynamically regulated during cortical development, and suggest that the multiple neurotrophins expressed in developing cortex represent distinct components of an extracellular signaling system for regulating dendritic growth.

Animals↗
PubMed1997

Relationships between local synaptic connections and orientation domains in primary visual cortex.

Combined optical imaging of ferret primary visual cortex in vivo and scanning laser photostimulation in brain slices were used to determine the spatial relationships between synaptic inputs onto individual neurons and the pattern of orientation columns. In the upper cortical layers, both excitatory and inhibitory inputs originated primarily from regions with orientation tuning similar to that of the recorded neurons; the shapes of the input tuning curves were indistinguishable. The orientation distributions of both types of inputs centered around the orientation of the recorded neurons, and no evidence for preferential cross-orientation inputs, either excitatory or inhibitory, was observed. These patterns of synaptic connectivity are most consistent with feedforward models for generation of orientation selectivity and are inconsistent with the patterns required by models based on cross-orientation inhibition.

Animals↗
PubMed1997

Focal delivery of neurotrophins into the central nervous system using fluorescent latex microspheres.

A new technique for in vivo and in vitro delivery of neurotrophins is described. The method is based upon the ability of certain fluorescent latex microspheres to adsorb large quantities of neurotrophin and then release the factor for at least three to four days. Injection of such neurotrophin-coated microspheres in vivo provides focal delivery of neurotrophins to distinct populations of neurons. The fluorescence of the microspheres accurately identifies the region of neurotrophin treatment in vivo; two independent methods indicate that microsphere-born proteins do not diffuse significantly beyond the site of injection. In addition to providing focal delivery and labeling of the site of application, labeled microspheres are retrogradely transported by neurons; thus, neurons whose distant terminals are exposed to neurotrophin can be identified and analyzed. This approach provides a powerful method for the introduction of neuroactive proteins into defined and localized regions of the central nervous system.

Animals↗
PubMed1997

Up your nose.

Explore the source record for details and available documents.

Child↗
PubMed1996

Synaptic activity and the construction of cortical circuits.

Vision is critical for the functional and structural maturation of connections in the mammalian visual system. Visual experience, however, is a subset of a more general requirement for neural activity in transforming immature circuits into the organized connections that subserve adult brain function. Early in development, internally generated spontaneous activity sculpts circuits on the basis of the brain's "best guess" at the initial configuration of connections necessary for function and survival. With maturation of the sense organs, the developing brain relies less on spontaneous activity and increasingly on sensory experience. The sequential combination of spontaneously generated and experience-dependent neural activity endows the brain with an ongoing ability to accommodate to dynamically changing inputs during development and throughout life.

Action Potentials↗
PubMed1996

Neurotrophin regulation of cortical dendritic growth requires activity.

Neurotrophins have been proposed to mediate several forms of activity-dependent competition in the central nervous system. A key element of such hypotheses is that neurotrophins act preferentially on active neurons; however, little direct evidence supports this postulate. We therefore examined, in ferret cortical brain slices, the interactions between activity and neurotrophins in regulating dendritic growth of layer 4 pyramidal neurons. Inhibition of spontaneous electrical activity, synaptic transmission, or L-type calcium channels each prevented the otherwise dramatic increase in dendritic arborizations elicited by brain-derived neurotrophic factor. In developing cortex, this requirement for conjoint neurotrophin signaling and activity provides a mechanism for selectively enhancing the growth and connectivity of active neurons.

Animals↗
PubMed1995

NT-4-mediated rescue of lateral geniculate neurons from effects of monocular deprivation.

Altering the balance of activity between the two eyes during the critical period for visual-system development profoundly affects competitive interactions among neurons in the lateral geniculate nucleus and primary visual cortex. Neurons in the lateral geniculate nucleus that are deprived of activity by closing or silencing one eye atrophy as a result of competition with non-deprived neurons for some critical factor(s) presumed to be present in the cortex. Based on their actions in the developing visual system, neurotrophins are attractive candidates for such factors. We tested whether neurotrophins mediate intracortical competition of afferents from the lateral geniculate nucleus by using monocular deprivation and a new method for highly localized, in vivo delivery of neurotrophins. This method allowed unambiguous identification of neurons that were exposed to neurotrophin. Here we report that only one neurotrophin, the TrkB ligand NT-4, rescued neurons in the lateral geniculate nucleus from the dystrophic effects of monocular deprivation.

Animals↗
PubMed1995

Emergence of functional circuits in ferret visual cortex visualized by optical imaging.

The emergence of functional lateral interactions in ferret visual cortex was monitored using high speed optical imaging of voltage-sensitive dye signals in brain slices. Prior to the time of eye opening, lateral activation was restricted to a narrow columnar region. During the week following eye opening, the extent of lateral propagation of activity more than doubled. Selective interruption of specific pathways in the slice, combined with pharmacological and anatomical experiments, determined that this lateral propagation was mediated by horizontal projections made within layer 2/3. These results indicate that functional horizontal interactions emerge only after axons begin branching and in parallel with, but not prior to, the refinement of orientation selectivity.

Age Factors↗
PubMed1995

Patterns of excitation and inhibition evoked by horizontal connections in visual cortex share a common relationship to orientation columns.

Combined optical imaging and electrophysiological techniques were used to assess directly the functional nature of long-range excitatory and inhibitory synaptic interactions between orientation columns in area 17 of ferret visual cortex. A significant correlation was found between the layout of iso-orientation columns and the pattern of evoked synaptic inputs between cortical sites: the largest-amplitude inhibitory and excitatory synaptic responses were evoked in single neurons when stimulation and recording electrodes were located in orientation columns sharing the same angle preference. Both excitatory and inhibitory synaptic responses decreased in amplitude when stimulation and recording electrodes were located in orientation columns with orthogonal angle preferences. Changing the stimulus intensity altered the balance of evoked excitation and inhibition without changing the columnar specificity of inputs. These results directly demonstrate that horizontal connections modulate both excitatory and inhibitory synaptic interactions between iso-orientation columns.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1995

Neurotrophins regulate dendritic growth in developing visual cortex.

Although dendritic growth and differentiation are critical for the proper development and function of neocortex, the molecular signals that regulate these processes are largely unknown. The potential role of neurotrophins was tested by treating slices of developing visual cortex with NGF, BDNF, NT-3, or NT-4 and by subsequently visualizing the dendrites of pyramidal neurons using particle-mediated gene transfer. Specific neurotrophins increased the length and complexity of dendrites of defined cell populations. Basal dendrites of neurons in each cortical layer responded most strongly to a single neurotrophin: neurons in layer 4 to BDNF and neurons in layers 5 and 6 to NT-4. In contrast, apical dendrites responded to a range of neurotrophins. On both apical and basal dendrites, the effects of the TrkB receptor ligands, BDNF and NT-4, were distinct. The spectrum of neurotrophic actions and the laminar specificity of these actions implicate endogenous neurotrophins as regulatory signals in the development of specific dendritic patterns in mammalian neocortex.

Animals↗
PubMed1995

Neuronal domains in developing neocortex: mechanisms of coactivation.

The mammalian neocortex consists of columnar circuits, whose development may be controlled by patterns of spontaneous activity. Columnar domains of spontaneously coactive neurons were previously described using Ca2+ imaging of slices from developing rat neocortex. We have now investigated the cellular mechanisms responsible for the coactivation of these domains. The activation starts in the center of a domain and spreads at speeds of approximately 100 microns/s. Domains occur in the presence of tetrodotoxin but are blocked by the gap junction blockers halothane and octanol. Simultaneous intracellular and optical recordings from dye-coupled cells reveal functional coupling between developing neocortical neurons. These data support the hypothesis that a neuronal domain results from the spontaneous excitation of one or a few trigger neurons that subsequently activate, either electrically or biochemically, the rest of the cells via gap junctions.

Animals↗
PubMed1995

Neuronal coupling and uncoupling in the developing nervous system.

Sensitive new tracers and imaging techniques have revealed that gap junction coupling during brain development is much more pronounced than previously believed. Recent results demonstrate that cell coupling can produce functional neuron assemblies characterized by synchronized fluctuations in the cytosolic Ca2+ concentration. Coupling is especially pronounced before and during the period of synapse formation and initial establishment of neuronal circuits. Thus, communication via gap junctions may generate coordinated electrical or biochemical activity before the onset of synaptic transmission, and thereby provide the outlines of functional architecture in the developing brain.

Animals↗
PubMed1994

Rearrangements of synaptic connections in visual cortex revealed by laser photostimulation.

Assessing patterns of synaptic connections in the developing mammalian neocortex has relied primarily on anatomical studies. In a physiological approach described here, the patterns of synaptic connections in slices of developing ferret visual cortex were determined with scanning laser photostimulation. Functional synaptic inputs to pyramidal cells in cortical layers 2 and 3 originating from sites close to the neuronal cell body appeared at least 2 weeks before eye opening, prior to the formation of long-range horizontal connections. Extensive long-range horizontal connections appeared in the next 10 days of development. The number of local connections peaked at the time of eye opening; the number of these connections subsequently declined to the level found in the adult while the specificity of long-distance connections increased. Thus, the relative influence of local connections on the activity of layer 2 and layer 3 neurons declines as the cortex matures while the influence of longer range connections increases substantially.

Animals↗
PubMed1994

Scanning laser photostimulation: a new approach for analyzing brain circuits.

A new technique for understanding the organization of complex circuits in the vertebrate brain, scanning laser photostimulation, is described. This approach is based on the photolysis of a caged form of the excitatory neurotransmitter glutamate. Computer-controlled photostimulation and whole cell recording in brain slices allow the construction of detailed maps of the position, strength, sign and number of inputs converging on a single postsynaptic neuron. Scanning laser photostimulation offers many advantages over current techniques: spatial resolution is superb, fibers of passage are not activated, and thousands of presynaptic locations can be stimulated. This review describes the technique of photostimulation, outlines the instrumentation, necessary to implement it, and discusses the interpretation of photostimulation-derived data. Several examples of applications, ranging from mapping circuits in the mammalian visual cortex to determining receptor distributions on single neurons are considered. Although still in its early stages, scanning laser photostimulation offers neuroscientists a powerful tool for determining the organization and function of local brain circuits.

Action Potentials↗
PubMed1994

Neuronal transfection in brain slices using particle-mediated gene transfer.

Difficulties in neuronal transfection continue to restrict the applicability of molecular approaches to neurobiology. Conventional transfection techniques have been of limited effectiveness, particularly in intact neural tissues. Viral vectors effectively transfect neurons both in vitro and in vivo but are labor intensive to construct, difficult to control, and often compromise cell viability. We describe here an alternative strategy using particle-mediated gene transfer for the transfection of neurons and glia in intact brain slices. This approach is efficient, reliable, and does not require advanced molecular biological facilities for its application.

Animals↗
PubMed1994

Body position affects recumbent postprandial reflux.

There is a lack of consensus as to whether there is a difference in the amount of gastroesophageal reflux when lying with the right versus the left side down. In an attempt to answer this question we conducted a two-part study. The first consisted of a questionnaire distributed to 103 gastroenterologists with a special interest in the esophagus. The second was a randomized study in 20 normal subjects given a high-fat meal to induce reflux. Postprandial reflux was monitored by esophageal pH testing for 4 h after random assignment to either the left or right lateral decubitus position (left or right side down) on different days. Of the 87 gastroenterologists responding to our survey, 45 were uncertain as to which position was associated with worse reflux. Among the 42 who did specify, 27 (64%) favored the right lateral decubitus position as associated with more reflux symptoms. The direct comparison of the two positions demonstrated that the total amount of reflux time was significantly (p < 0.05) greater with subjects in the right decubitus position (231 min) than in the left (117 min). Although total episodes of reflux were greater when lying on the right side (227), compared with the left (198), the difference was not significant. In addition, average overall acid clearance was significantly (p < 0.001) prolonged with right side down (0.77 +/- 0.14 min/episode) compared with left side down (0.29 +/- 0.08 min/episode).

Adult↗