Jens Midtgaard

Processing of information from different sources : spatial synaptic integration in the dendrites of vertebrate CNS neurons

Most synapses on a neuron are distributed along the dendrites. Inputs from different types of presynaptic neurons often distribute to different dendritic compartments. This provides an anatomical framework for spatial synaptic integration. At the same time, a plethora of time- and voltage-dependent responses are present, usually with a distinct distribution over the somato-dendritic membrane. These intrinsic conductances shape the local dendritic response to ligand-gated conductances, and provide the dendrites with a dynamic way of regulating the interaction between synapses. Recent results from neurons in the vertebrate CNS exemplify these mechanisms of dendritic integration.

Presynaptic calcium signalling in cerebellar mossy fibres.

Whole-cell recordings were obtained from mossy fibre terminals in adult turtles in order to characterize the basic membrane properties. Calcium imaging of presynaptic calcium signals was carried out in order to analyse calcium dynamics and presynaptic GABA B inhibition. A tetrodotoxin (TTX)-sensitive fast Na+ spike faithfully followed repetitive depolarizing pulses with little change in spike duration or amplitude, while a strong outward rectification dominated responses to long-lasting depolarizations. High-threshold calcium spikes were uncovered following addition of potassium channel blockers. Calcium imaging using Calcium-Green dextran revealed a stimulus-evoked all-or-none TTX-sensitive calcium signal in simple and complex rosettes. All compartments of a complex rosette were activated during electrical activation of the mossy fibre, while individual simple and complex rosettes along an axon appeared to be isolated from one another in terms of calcium signalling. CGP55845 application showed that GABA B receptors mediated presynaptic inhibition of the calcium signal over the entire firing frequency range of mossy fibres. A paired-pulse depression of the calcium signal lasting more than 1 s affected burst firing in mossy fibres; this paired-pulse depression was reduced by GABA B antagonists. While our results indicated that a presynaptic rosette electrophysiologically functioned as a unit, topical GABA application showed that calcium signals in the branches of complex rosettes could be modulated locally, suggesting that cerebellar glomeruli may be dynamically sub-compartmentalized due to ongoing inhibition mediated by Golgi cells. This could provide a fine-grained control of mossy fibre-granule cell information transfer and synaptic plasticity within a mossy fibre rosette.

NERVE CELLS AS SOURCE OF TIME SCALE AND PROCESSING DENSITY IN BRAIN FUNCTION

So far, neural networks have been treated with emphasis on connectivity and synaptic strengths. It is obvious, however, that the response properties of the postsynaptic elements also play a crucial role for the overall performance of a network. Drawing mainly from our own experiments on nerve cells we illustrate how sophisticated response properties dedicate nerve cells to produce desired outputs, enhance processing density and provide time scale to network operations. We note that the response properties are specific for each cell type and open to modification by intrinsic activity and by certain classes of input. It is suggested that adopting new performance in some cases may be better served by changes in postsynaptic response properties rather than by changing synaptic strengths.

Complex information processing in real neurones

Although networks of real and modelled neurones have much in common they are studied for very different reasons and in very different ways. Brains are historical entities handed over by the process of natural selection and shaped by their individual lives. They are given and we are well aware of their overall abilities to direct body function and movement and to provide sensation, mental activity and social interaction. Apart from how brains are put together during development the key question in neurobiology is — not what they do — but how they do it!