Neurons are the basic cellular units of the brain, and are connected
via synapses to form neural networks. One of the central questions
in neuroscience is how particular tasks, or "computations",
are implemented by neural networks to generate behaviour, and
how patterns of activity are stored during learning. In the
past, the prevailing view has been that information processing
and storage in neural networks results mainly from properties
of synapses and connectivity of neurons within the network.
As a consequence, the contribution of single neurons to computation
in the brain has long been underestimated. Recent work has shown,
however, that the dendritic processes of single neurons, which
receive most of the synaptic input, display an extremely rich
repertoire of behaviour, and actively integrate their synaptic
inputs to define the input-output relation of the neuron (1).
Furthermore, the signalling mechanisms which have been discovered
in dendrites have suggested new ways in which patterns of network
activity could be stored and transmitted (2). These advances
have refocused attention on how single neurons contribute to
information processing and storage in the brain. The recent
development of new experimental and theoretical techniques now
offers the promise to link single-cell processing with higher
levels of brain function.
Our group is interested in understanding the cellular basis
of neural computation, focusing on dendritic function and processing
of synaptic input in relation to network activity in the intact
brain. We are integrating approaches and techniques at different
levels of brain function to study the cellular basis of information
processing in the cerebellar and cerebral cortex. Our focus
is on cerebellar Purkinje cells (3, 4) and cortical layer 5
pyramidal cells (5), which are the principal neurons in their
respective networks. Techniques used include direct patch-clamp
recordings from neuronal dendrites (figure 1), imaging ionic
signals in dendrites and spines with two-photon laser-scanning
microscopy (figure 2), and recording from multiple synaptically
connected cells (figure 3). These techniques are applied in
parallel to in-vitro and in-vivo preparations in order to investigate
the details of cellular mechanisms while placing them in the
context of network activity. The experimental approaches are
being complemented by state-of-the-art modelling of cellular
signalling and the dynamics of synaptic integration. At each
stage of our work, our aim is to measure, using combined imaging
and electrophysiological approaches, dendritic signals in vivo
triggered by sensory processing, in order to ultimately link
cellular mechanisms to behaviour.
