Phase response properties of hippocampal neurons

A fundamental challenge in neuroscience is to understand memory, i.e. how information can be stored in and retrieved from a neural circuit. Whereas synaptic plasticity is likely to contribute to memory storage, the cellular basis of the retrieval process has not been studied. The aim of the present project is to study fundamental cellular processes underlying retrieval of information from the hippocampus, known to be necessary for certain types of memory. During memory processing, the hippocampal network enters a state of characteristic oscillations of around 5 Hz, referred to as theta activity, and it is believed that information can be represented by the timing of spikes in individual neurons relative to this network oscillation. Here we would study how information can be retrieved in individual neurons by the phase of firing induced by a transient stimulus. The property of the neuron that allows this to happen is the so-called phase response curve (PRC), which defines the timing of the spike relative to the on-going oscillation. We hope that this way of analysing neuronal properties can give us new insight into memory, both for the basic understanding of information storage in the brain, for the possiblity of developing new treatments of memory disorders, and for the possibility that similar principles can be used powerfully in computers.

The task of storing and retrieving memories is fundamental for the brain. Whereas possible cellular mechanisms underlying memory storage have been studied in detail, very little information is available on the mechanisms underlying memory retrieval. At a cellular level, retrieved information can be encoded by changes in the neuronal firing rate and/or changes in the timing of individual action potentials. Here, we will use phase response curves to characterise how information stored as distributed changes in synaptic weights can be retrieved as the timing of action potentials relative to an underlying network oscillation. The objectives are to characterise phase response properties of pyramidal neurons, study the underlying mechanisms, and compare and contrast them with different classes of interneurons. This will be studied using whole-cell patch-clamp recording in acute hippocampal slices in combination with dynamic clamp. The results should give us new insights into how the network dynamics can assist memory processing in the brain.