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Tobias Bonhoeffer

Publications and source records attributed to Tobias Bonhoeffer.

11 recordsLinked to original sources
PubMed2004

High-resolution functional optical imaging: from the neocortex to the eye.

Much work remains to be done to establish the clinical usefulness of the RFI for early diagnosis and treatment guidance. The discoveries obtained by functional optical imaging of the neocortex in the last 15 years and the recent RFI studies of the eyes of normal subjects and patients with diabetic retinopathy, glaucoma, and age-related macular degeneration suggest that functional optical imaging of the retina is likely to become a multi-modality powerful clinical tool.

Animals↗
PubMed2003

Hippocampal plasticity requires postsynaptic ephrinBs.

Chemical synapses contain specialized pre- and postsynaptic structures that regulate synaptic transmission and plasticity. EphB receptor tyrosine kinases are important molecular components in this process. Previously, EphB receptors were shown to act postsynaptically, whereas their transmembrane ligands, the ephrinBs, were presumed to act presynaptically. Here we show that in mouse hippocampal CA1 neurons, the Eph/ephrin system is used in an inverted manner: ephrinBs are predominantly localized postsynaptically and are required for synaptic plasticity. We further demonstrate that EphA4, a candidate receptor, is also critically involved in long-term plasticity independent of its cytoplasmic domain, suggesting that ephrinBs are the active signaling partner. This work raises the intriguing possibility that depending on the type of synapse, Eph/ephrins can be involved in activity-dependent plasticity in converse ways, with ephrinBs on the pre- or the postsynaptic side.

Animals↗
PubMed2003

Brain mapping: new wave optical imaging.

Optical imaging of intrinsic signals is widely used for high-resolution brain mapping in various animal species. A new approach using continuous data acquisition and Fourier decomposition of the signal allows for much faster mapping, opening up the possibility of applying this method to new experimental questions.

Animals↗
PubMed2003

Synaptopodin-deficient mice lack a spine apparatus and show deficits in synaptic plasticity.

The spine apparatus is a cellular organelle that is present in many dendritic spines of excitatory neurons in the mammalian forebrain. Despite its discovery >40 years ago, the function of the spine apparatus is still unknown although calcium buffering functions as well as roles in synaptic plasticity have been proposed. We have recently shown that the 100-kDa protein synaptopodin is associated with the spine apparatus. Here, we now report that mice homozygous for a targeted deletion of the synaptopodin gene completely lack spine apparatuses. Interestingly, this absence of the spine apparatus is accompanied by a reduction in hippocampal long-term potentiation (LTP) in the CA1 region of the hippocampus and by an impairment of spatial learning in the radial arm maze test. This genetic analysis points to a role of the spine apparatus in synaptic plasticity.

Animals↗
PubMed2002

Mechanism of TrkB-mediated hippocampal long-term potentiation.

The TrkB receptor tyrosine kinase and its ligand, BDNF, have an essential role in certain forms of synaptic plasticity. However, the downstream pathways required to mediate these functions are unknown. We have studied mice with a targeted mutation in either the Shc or the phospholipase Cgamma (PLCgamma) docking sites of TrkB (trkB(SHC/SHC) and trkB(PLC/PLC) mice). We found that hippocampal long-term potentiation was impaired in trkB(PLC/PLC) mice, but not trkB(SHC/SHC) mice. BDNF stimulation of primary neurons derived from trkB(PLC/PLC) mice fully retained their ability to activate MAP kinases, whereas induction of CREB and CaMKIV phosphorylation was strongly impaired. The opposite effect was observed in trkB(SHC/SHC) neurons, suggesting that MAPKs and CREB act in parallel pathways. Our results provide genetic evidence that TrkB mediates hippocampal plasticity via recruitment of PLCgamma, and by subsequent phosphorylation of CaMKIV and CREB.

Active Transport, Cell Nucleus↗
PubMed2002

Spine motility. Phenomenology, mechanisms, and function.

Throughout the history of neuroscience, dendritic spines have been considered stable structures, but in recent years, imaging techniques have revealed that spines are constantly changing shape. Spine motility is difficult to categorize, has different forms, and possibly even represents multiple phenomena. It is influenced by synaptic transmission, intracellular calcium, and a multitude of ions and other molecules. An actin-based cascade mediates this phenomenon, and while the precise signaling pathways are still unclear, the Rho family of GTPases could well be a "common denominator" controlling spine morphology. One role of spine motility might be to enable a searching function during synaptogenesis, allowing for more efficacious neuronal connectivity in the neuronal thicket. This idea revisits concepts originally formulated by Cajal, who proposed over a hundred years ago that spines might help to increase and modify synaptic connections.

Animals↗
PubMed2002

Mapping retinotopic structure in mouse visual cortex with optical imaging.

We have used optical imaging of intrinsic signals to visualize the retinotopic organization of mouse visual cortex. The functionally determined position, size, and shape of area 17 corresponded precisely to the location of this area as seen in stained cortical sections. The retinotopic map, which was confirmed with electrophysiological recordings, exhibited very low inter-animal variability, thus allowing averaging of maps across animals. Patches of activity in area 17 were often encircled by regions in which the intrinsic signal dropped below baseline, suggesting the presence of strong surround inhibition. Single-unit recordings revealed that this decrease of the intrinsic signal indeed correlated with a drop of neuronal firing rate below baseline. The averaged maps also greatly facilitated the identification of extrastriate visual activity, pointing to at least four extrastriate visual areas in the mouse. We conclude that optical imaging is ideally suited to visualize retinotopic maps in mice, thus making this a powerful technique for the analysis of map structure in transgenic animals.

Animals↗
PubMed2002

Correlated binocular activity guides recovery from monocular deprivation.

Monocular deprivation (MD) has much more rapid and severe effects on the ocular dominance of neurons in the primary visual cortex (V1) than does binocular deprivation. This finding underlies the widely held hypothesis that the developmental plasticity of ocular dominance reflects competitive interactions for synaptic space between inputs from the two eyes. According to this view, the relative levels of evoked activity in afferents representing the two eyes determine functional changes in response to altered visual experience. However, if the deprived eye of a monocularly deprived kitten is simply reopened, there is substantial physiological and behavioural recovery, leading to the suggestion that absolute activity levels, or some other non-competitive mechanisms, determine the degree of recovery from MD. Here we provide evidence that correlated binocular input is essential for such recovery. Recovery is far less complete if the two eyes are misaligned after a period of MD. This is a powerful demonstration of the importance of cooperative, associative mechanisms in the developing visual cortex.

Animals↗
PubMed2002

Orientation specificity of contrast adaptation in visual cortical pinwheel centres and iso-orientation domains.

Exposure to a high-contrast visual stimulus causes adaptation, a psychophysical phenomenon that is quite selective for stimulus orientation. Its mechanism is largely cortical but the underlying circuitry is still not unambiguously resolved. It has been suggested that adaptation could be the result of integration of inputs from cells within a large local pool, effectively scaling their outputs with respect to local contrast. In this case, orientation selectivity of neuronal adaptation should depend on the location of neurons within the cortical map of orientation preference. We tested this hypothesis by quantifying adaptation to optimally oriented and to orthogonal-to-optimum gratings among neurons recorded either from iso-orientation domains or orientation pinwheel centres, as identified by optical imaging of cat visual cortex. We did not find a significant difference in adaptation characteristics for these two populations of cells, implying that these characteristics do not depend on the local functional architecture. Surprisingly, however, we additionally observed that under isoflurane (but not halothane) anaesthesia, most neurons exhibited adaptation by cross-oriented gratings, regardless of their location within the orientation map. It seems likely that, under isoflurane, inputs became visible that were masked by the commonly used, deeper halothane anaesthesia. For individual cells, the presence of these inputs was independent of their location within the cortical orientation map.

Action Potentials↗