Albrecht Kossel

A caged Ab reveals an immediate/instructive effect of BDNF during hippocampal synaptic potentiation

Neurotrophins have been shown to be involved in functional strengthening of central nervous system synapses. Although their general importance in this process is undisputed, it remains unresolved whether neurotrophins are truly mediators of synaptic strengthening or merely important cofactors. To address this question, we have devised a method to inactivate endogenous brain-derived neurotrophic factor (BDNF) with high time resolution by “caging” a function-blocking mAb against BDNF with a photosensitive protecting compound. Different assays were used to show that this inactivation of the Ab is reversible by UV light. Synaptic potentiation after τ-burst stimulation in the CA1 region of acute hippocampal slices was significantly less when applying the unmodified Ab compared with the caged Ab. Importantly, photoactivation of the caged Ab during the time of induction of synaptic enhancement led to a marked decrease in potentiation. Our experiments therefore strengthen the view that endogenous BDNF has fast effects during induction of synaptic plasticity. The results additionally show that caged Abs can provide a tool for precise spatiotemporal control over endogenous protein levels.

Non-Hebbian synapses in rat visual cortex.

In the mammalian CNS, long term potentiation can be induced by repeatedly pairing presynaptic stimulation with postsynaptic depolarization of a single cell, similar to a model proposed by Hebb, that synaptic strengthening occurs as a result of correlated pre- and postsynaptic activity. However, our experiments indicate that the Hebbian rule is not strictly valid in the cortex. Double intracellular recordings showed that synaptic reinforcement is not confined to the depolarized postsynaptic neuron, but is also observed in adjacent but not coactivated neurons. The enhancement and its spread is stimulus-specific, it occurs only for fibres stimulated during the pairing procedure. During development, this spread might lead to a characteristic organizing principle of the cortex, the clustering of cells with similar functional properties.

Effects of NMDA antagonists on developmental plasticity in kitten visual cortex

The existence of Hebb synapses in the visual cortex of young kittens has long been postulated. A mechanism for the correlation of activity in simultaneously active pre‐ and postsynaptic neurons could be provided by the properties of the N‐methyl‐d‐aspartate (NMDA) receptor and its associated Ca2+ channel, which opens in a transmitter‐ and voltage‐dependent manner. We have studied the effects on cortical plasticity of blocking NMDA receptors in different ways with competitive and non‐competitive NMDA antagonists.

Calcium-dependent alterations in dendritic architecture of hippocampal pyramidal neurons

Dendritic arbor formation and the underlying mechanisms are crucial for the functional connectivity and plasticity of neurons. We used a focal electric field to locally raise calcium levels in individual dendritic shafts of isolated hippocampal pyramidal neurons, in order to develop an accessible system for studying dendritic branch formation, and to test the role of calcium as an intrinsic signal that may participate in arborization. Filopodia were induced in a manner temporally and spatially related to induced calcium rises. Certain filopodia also thickened and were transformed into dendritic branches. These results suggest that calcium-mediated signaling can induce branching in dendrites, and describe an accessible system for studying the intracellular machinery that drives dendritic arborization.