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T Bonhoeffer

Publications and source records attributed to T Bonhoeffer.

At least 19 recordsLinked to original sources
PubMed1997

Synapse specificity of long-term potentiation breaks down at short distances.

Long-term potentiation (LTP), the long-lasting increase in synaptic transmission, has been proposed to be a cellular mechanism essential for learning and memory, neuronal development, and circuit reorganization. In the original theoretical and experimental work it was assumed that only synapses that had experienced concurrent pre- and postsynaptic activity are subject to synaptic modification. It has since been shown, however, that LTP is also expressed in synapses on neighbouring neurons that have not undergone the induction procedure. Yet, it is still believed that this spread of LTP is limited to adjacent postsynaptic cells, and does not occur for synapses on neighbouring input fibres. However, for technical reasons, tests for 'input specificity' were always done for synapses relatively far apart. Here we have used a new local superfusion technique, which allowed us to assess the synaptic specificity of LTP with a spatial resolution of approximately 30 microm. Our results indicate that there is no input specificity at a distance of less than 70 microm. Synapses in close proximity to a site of potentiation are also potentiated regardless of their own history of activation, whereas synapses far away show no potentiation.

Animals↗
PubMed1997

Functional specificity of long-range intrinsic and interhemispheric connections in the visual cortex of strabismic cats.

The development of both long-range intracortical and interhemispheric connections depends on visual experience. Previous experiments showed that in strabismic but not in normal cats, clustered horizontal axon projections preferentially connect cell groups activated by the same eye. This indicates that there is selective stabilization of fibers between neurons exhibiting correlated activity. Extending these experiments, we investigated in strabismic cats: (1) whether tangential connections remain confined to columns of similar orientation preference within the subsystems of left and right eye domains; and (2) whether callosal connections also extend predominantly between neurons activated by the same eye and preferring similar orientations. To this end, we analyzed in strabismic cats the topographic relationships between orientation preference domains and both intrinsic and callosal connections of area 17. Red and green latex microspheres were injected into monocular iso-orientation domains identified by optical imaging of intrinsic signals. Additionally, domains sharing the ocular dominance and orientation preference of the neurons at the injection sites were visualized by 2-deoxyglucose (2-DG) autoradiography. Quantitative analysis revealed that 56% of the retrogradely labeled cells within the injected area 17 and 60% of the transcallosally labeled neurons were located in the 2-DG-labeled iso-orientation domains. This indicates: (1) that strabismus does not interfere with the tendency of long-range horizontal fibers to link predominantly neurons of similar orientation preference; and (2) that the selection mechanisms for the stabilization of callosal connections are similar to those that are responsible for the specification of the tangential intrinsic connections.

Animals↗
PubMed1997

Orientation selectivity in pinwheel centers in cat striate cortex.

In primary visual cortex of higher mammals neurons are grouped according to their orientation preference, forming "pinwheels" around "orientation centers." Although the general structure of orientation maps is largely resolved, the microscopic arrangement of neuronal response properties in the orientation centers has remained elusive. The tetrode technique, enabling multiple single-unit recordings, in combination with intrinsic signal imaging was used to reveal the fine-grain structure of orientation maps in these locations. The results show that orientation centers represent locations where orientation columns converge containing normal, sharply tuned neurons of different orientation preference lying in close proximity.

Action Potentials↗
PubMed1997

Spatio-temporal frequency domains and their relation to cytochrome oxidase staining in cat visual cortex.

Spatial and temporal frequencies are important attributes of the visual scene. It is a long-standing question whether these attributes are represented in a spatially organized way in cat primary visual cortex. Using optical imaging of intrinsic signals, we show here that grating stimuli of different spatial frequencies drifting at various speeds produce distinct activity patterns. Rather than observing a map of continuously changing spatial frequency preference across the cortical surface, we found only two distinct sets of domains, one preferring low spatial frequency and high speed, and the other high spatial frequency and low speed. We compared the arrangement of these spatio-temporal frequency domains with the cytochrome oxidase staining pattern, which, based on work in primate striate cortex, is thought to reflect the partition of the visual cortex into different processing streams. We found that the cytochrome oxidase blobs in cat striate cortex coincide with domains engaged in the processing of low spatial and high temporal frequency contents of the visual scene. Together with other recent results, our data suggest that spatiotemporal frequency domains are a manifestation of parallel streams in cat visual cortex, with distinct patterns of thalamic inputs and extrastriate projections.

Animals↗
PubMed1997

Rapid gene transfer into cultured hippocampal neurons and acute hippocampal slices using adenoviral vectors.

Primary cultures of hippocampal neurons were infected with an adenovirus coding for beta-galactosidase. Expression could be detected as early as 4 h after infection and steadily increased to high levels at 24 h without evidence for a functional impairment of the infected neurons. Similarly, adenovirus-mediated gene transfer into acute hippocampal slices was detectable 4 h after infection and could be localized to discrete areas of the CA1 region by microinjection of the virus stock solution. Infected slices were still suitable for electrophysiological experiments.

Adenoviridae↗
PubMed1997

Development of orientation preference maps in area 18 of kitten visual cortex.

We investigated the development of orientation preference maps in the visual cortex of kittens by repeated optical imaging from the same animal. Orientation maps became detectable for the first time around postnatal day (P) 17 and improved continuously in strength unitl P30, the time at which their appearance became adultlike. During this developmental period the overall geometry of the maps remained unchanged, suggesting that the layout of the orientation map is specified prior to P17. Hence, before the visual cortex becomes susceptible to experience-dependent modifications its functional architecture is largely specified. This suggests that the initial development and layout of orientation preference maps are determined by intrinsic processes that are independent of visual experience. This conclusion is further supported by the result that orientation maps were well expressed at P24 in binocularly deprived kittens. Because the appearance of the first orientation-selective neurons and the subsequent development of orientation preference maps correlated well with the time course of the expression and refinement of clustered horizontal connections, we propose that these connections might contribute to the specification of orientation preference maps.

Animals↗
PubMed1996

Virus-mediated gene transfer into hippocampal CA1 region restores long-term potentiation in brain-derived neurotrophic factor mutant mice.

Long-term potentiation (LTP) has been shown to be impaired in mice deficient in the brain-derived neurotrophic factor (BDNF) gene, as well as in a number of other knockout animals. Despite its power the gene-targeting approach is always fraught with the danger of looking at the cumulative direct and indirect effects of the absence of a particular gene rather than its immediate function. The re-expression of a specific gene at a selective time point and at a specific site in gene-defective mutants presents a potent procedure to overcome this limitation and to evaluate the causal relationship between the absence of a particular gene and the impairment of a function in gene-defective animals. Here we demonstrate that the re-expression of the BDNF gene in the CA1 region almost completely restores the severely impaired LTP in hippocampal slices of BDNF-deficient mice. The results therefore provide strong evidence for the direct involvement of BDNF in the process of LTP.

Adenoviridae↗
PubMed1996

Development of orientation preference maps in ferret primary visual cortex.

The development of orientation preference maps was studied in ferret primary visual cortex using chronic optical imaging of intrinsic signals. The emergence and maturation of the maps were examined over time in single animals. The earliest age at which cortical domains selectively responsive to particular stimulus orientations were observed varied considerably between individuals, from postnatal day 31 to 36. In all cases, the earliest maps seen were low-contrast, with regions of orientation-specific activity that were difficult to distinguish from noise. These early maps matured over a period of several days into the high-contrast, patchy maps typical of adult animals. The structure of the orientation maps was remarkably constant over time. The indistinct features in the earliest maps were always patches of the same sizes and shapes and at the same locations as in the maps obtained in subsequent recording sessions. Details of the more mature maps, including the relative intensities of individual iso-orientation domains, were also constant from one recording session to another over periods of several weeks. The patterning of iso-orientation domains in ferret primary visual cortex thus is established early in development and remains stable over time, unaffected by either normal visual experience or the anatomical rearrangements of geniculocortical afferents into eye-specific domains.

Age Distribution↗
PubMed1996

Development of identical orientation maps for two eyes without common visual experience.

In the mammalian visual cortex, many neurons are driven binocularly and response properties such as orientation preference or spatial frequency tuning are virtually identical for the two eyes. A precise match of orientation is essential in order to detect disparity and is therefore a prerequisite for stereoscopic vision. It is not clear whether this match is accomplished by activity-dependent mechanisms together with the common visual experience normally received by the eyes, or whether the visual system relies on other, perhaps even innate, cues to achieve this task. Here we test whether visual experience is responsible for the match in a reverse-suturing experiment in which kittens were raised so that both eyes were never able to see at the same time. A comparison of the layout of the two maps formed under these conditions showed them to be virtually identical. Considering that the two eyes never had common visual experience, this indicates that correlated visual input is not required for the alignment of orientation preference maps.

Animals↗
PubMed1996

A low-cost UV laser for flash photolysis of caged compounds.

Photolysis of caged compounds has become a standard tool for the rapid application of bioactive molecules. In principle this technique also allows to apply substances in a spatially very restricted manner. An important practical limitation for such experiments, however, is the high cost of UV lasers. Here we describe the assembly of an inexpensive pulsed nitrogen laser which is suitable for photolysis experiments. The laser which can be constructed in less than 1 week and for less than US$ 500 emits light pulses with a duration of approximately 5 ns, an energy of up to 200 microJ (= 40 kW) and a wavelength of 337 nm. Its beam can be focused to roughly 30 microns, a firing frequency of up to 50 Hz can be achieved, and electrical artifacts are minimal. These specifications make the laser optimally suited for most photolysis experiments. Its low price and ease of use should make the technique of spatially restricted flash photolysis amenable to many laboratories.

Animals↗
PubMed1996

The involvement of brain-derived neurotrophic factor in hippocampal long-term potentiation revealed by gene targeting experiments.

Brain-derived neurotrophic factor (BDNF) is a member of the NGF gene family, which has been shown to influence the survival and differentiation of specific classes of neurons in vitro and in vivo. The possibility that neurotrophins are also involved in processes of neuronal plasticity has only recently begun to receive attention. To determine whether BDNF has a function in processes like long-term potentiation (LTP), we produced a strain of mice with a deletion in the coding sequence of the BDNF-gene. We then used hippocampal slices from these mice to investigate whether LTP is affected by this mutation. Mutant mice showed significantly weaker LTP in the CA1 region. The magnitude of the potentiation as well as the percentage of cases in which LTP could be induced successfully was clearly reduced whereas important pharmacological and morphological control parameters in the hippocampus of these animals were unaffected. Adenoviral vectors were used to re-express BDNF in acute slices of BDNF-knock-out mice. In most cases LTP could be rescued with this approach. These results suggest that BDNF has an important functional role in the expression of LTP in the hippocampus.

Animals↗
PubMed1996

Neurotrophins and activity-dependent development of the neocortex.

A number of recent results suggest that neurotrophins play an important role in early development as well as in the later, activity-dependent processes important for the final shaping of cortical connections. Many neurotrophins and their receptors are regulated in parallel with the 'critical period' in development, and their application to the neocortex can dramatically alter the functional organization of the cortex, as well as the morphological properties of neocortical neurons. In addition, recent data show that a different phenomenon of synaptic plasticity, hippocampal long-term potentiation, also critically depends on neurotrophins. Thus, neurotrophins may play a role in linking functional modifications of synapses to the morphological effects of synaptic stabilization and rearrangement, as observed in the neocortex.

Animals↗
PubMed1995

Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor.

Brain-derived neurotrophic factor (BDNF), a member of the nerve growth factor (NGF) gene family, has been shown to influence the survival and differentiation of specific classes of neurons in vitro and in vivo. The possibility that neurotrophins are also involved in processes of neuronal plasticity has only recently begun to receive attention. To determine whether BDNF has a function in processes such as long-term potentiation (LTP), we produced a strain of mice with a deletion in the coding sequence of the BDNF gene. We then used hippocampal slices from these mice to investigate whether LTP was affected by this mutation. Homo- and heterozygous mutant mice showed significantly reduced LTP in the CA1 region of the hippocampus. The magnitude of the potentiation, as well as the percentage of cases in which LTP could be induced successfully, was clearly affected. According to the criteria tested, important pharmacological, anatomical, and morphological parameters in the hippocampus of these animals appear to be normal. These results suggest that BDNF might have a functional role in the expression of LTP in the hippocampus.

Animals↗
PubMed1995

Optical imaging of the layout of functional domains in area 17 and across the area 17/18 border in cat visual cortex.

Optical imaging based on intrinsic signals was used to investigate the functional architecture of cat area 17 and the border between areas 17 and 18. The visual stimuli were gratings of different spatial frequencies moving at different angles, in different directions and with different speeds. In area 17 the iso-orientation domains were usually organized in patches rather than as elongated bands. Patches with different orientation preferences were arranged radially forming 'pinwheels' around 'orientation centres'. The pinwheel density was approximately 1.7-fold higher than in area 18. To explore clustering according to direction of motion, stimuli having the same orientation but moving in opposite directions were used. These two stimuli yielded very similar activity maps giving no indication of robust directionality clustering. Using near infrared light we were able to simultaneously image ocular-dominance and iso-orientation domains. A quantitative assessment of the relative strengths of the two subsystems showed that in upper cortical layers clustering according to orientation preference was three-fold stronger than clustering according to ocular dominance. The functional organization of spatial frequency was also examined. When we compared the activated regions by stimuli having different spatial frequency and moving at different velocities we observed that neurons were clustered also in these respects. We also investigated the functional architecture at the area 17/18 border and found that orientation maps at both sides of the border were not independent of each other. The map of area 17 smoothly blended into that of area 18. Similarly, the preferred spatial frequency of the neurons changed gradually over a distance of approximately 0.8 mm at the region of the area 17/18 border.

Animals↗
PubMed1995

Optical imaging of intrinsic signals as a tool to visualize the functional architecture of adult and developing visual cortex.

One of the most common principles of cortical organization is that neurons with similar response properties are clustered together in space. Thereby the environment is represented in an orderly fashion on the cortical surface in a so-called "cortical map". In primary visual cortex, for instance, neurons with similar orientation preferences are grouped together, forming the orientation preference map. Optical imaging of intrinsic signals allows to investigate the organization of such maps in vivo. Neuronal activity was measured utilizing the fact that the transition from oxy-hemoglobin to hemoglobin in active brain areas can be detected optically by recording changes in light reflectance with a high resolution CCD-camera. When using this technique to look at the exact patterning of orientation preference maps in cat visual cortex a novel principle for the organization of cortical maps was observed: orientation was not organized in parallel bands as had previously been thought but iso-orientation domains were organized radially; orientations from 0 to 180 degrees were laid out in a pinwheel-like fashion around singularities which we termed "orientation-centers". After observing pinwheel patterns in orientation preference maps in adult cat visual cortex it was also investigated how these meticulously arranged maps develop in the cortex of young kittens. Performing chronical recordings in kittens from the age of postnatal day 17 on we were able to observe how orientation maps form already during the third week of life and--under normal conditions--remain largely unchanged thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Relationship between lateral inhibitory connections and the topography of the orientation map in cat visual cortex.

The functional and structural topography of lateral inhibitory connections was investigated in visual cortical area 18 using a combination of optical imaging and anatomical tracing techniques in the same tissue. Orientation maps were obtained by recording intrinsic signals in regions of 8.4-19 mm2. To reveal the inhibitory connections provided by large basket cells, biocytin was iontophoretically injected at identified orientation sites guided by the pattern of surface blood vessels. The axonal and dendritic fields of two retrogradely labelled large basket cells were reconstructed in layer III. Their axonal fields extended up to 1360 microns from the parent somata. In addition to single basket cells, the population of labelled basket cell axons was also studied. For this analysis anterogradely labelled basket axons running horizontally over 460-1280 microns from the core of an injection site in layer III were taken into account. The distribution of large basket cell terminals according to orientation preferences of their target regions was quantitatively assessed. Using the same spatial resolution as the orientation map, a frequency distribution of basket cell terminals dependent on orientation specificity could be derived. For individual basket cells, the results showed that, on average, 43% of the terminals provided input to sites showing similar orientation preferences (+/- 30 degrees) to those of the parent somata. About 35% of the terminals were directed to sites representing oblique-orientation [+/- (30-60) degrees], and 22% of them terminated at cross-orientation sites [+/- (60-90) degrees]. Furthermore, the possible impact of large basket cells on target cells at different distances and orientation preferences was estimated by comparing the occurrence of orientation preferences with the occurrence of basket terminals on the distance scale. It was found that a basket cell could elicit iso-orientation inhibition with a high impact between 100-400 and 800-1200 microns, strong cross-orientation inhibition at approximately 400-800 microns, and oblique-orientation inhibition between 300-500 and 700-900 microns from the parent soma. The non-isotropic topography of large basket axons suggests a complex function for this cell class, possibly including inhibition related to orientation and direction selectivity depending on the location of the target cells and possible target selectivity.

Animals↗