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The role of oscillations in the Hippocampal formation
John O'Keefe
University College London, London, UK
The electrical activity of the hippocampal formation is characterized
by several oscillatory potentials of different frequencies: theta (6
- 11 Hz), gamma (30 - 60 Hz), and high-frequency ripples (100- 200
Hz). In this talk I will discuss the functions of theta activity, one
of the best-known of these oscillations. I will argue that it has at
least three functions: 1) to bind together the activity of cells in
different parts of the hippocampal formation and more widely
distributed brain regions; 2) to set up the conditions for LTP or LTP
depending on the relationship of synaptic inputs to a given cell and
the phase of theta; and finally, 3) to provide one of the two
oscillators of different frequencies which interact to produce
interference patterns within the principal cells of the hippocampal
formation and which determine the temporal firing patterns in these
cells and their relationship to that of other cells. I will
concentrate primarily on the latter function. The first evidence for
interference patterns came from the phase precession effect originally
observed in CA1 pyramidal cells by O'Keefe and Recce in 1993, and now
known to exist in CA3 pyramids, layer 2 stellate cells of the
entorhinal cortex and, to a lesser extent, dentate granule cells. We
found that hippocampal pyramidal cells fired in bursts at
approximately the theta frequency as the rat ran through the place
field but that the preferred phase of firing did not remain constant
but instead moved to earlier phases with each successive burst.
Furthermore the phase of firing correlated had a higher correlation
with the animal's location within the field then with any other
variable, for example, time since entry into the field. We speculated
that this phase precession effect might be due to the interaction of
two oscillators of slightly different frequencies summing within the
pyramidal cell. This model would explain many of the observed
phenomena and in particular the fact that the phase precession often
continued in the second half of the field despite the fact that the
firing rate decreased at same time. An alternative was that the
precession effect was generated in the input structures to the
hippocampus and propagated into the hippocampus. Evidence in favor of
this latter view came from an experiment by Zugaro and Buzsaki who
showed that temporary silencing of pyramidal cells as the animal ran
through the field did not alter the relationship between phase and
location. When the cell resumed firing, it did so at the appropriate
phase for the animal's location in the field. The recent discovery of
grid cells in the medial entorhinal cortex by Hafting and Fyhn in the
Moser's lab opens up the possibility that they may be the source of
the phase precession. Grid cells fire with multiple place fields
located at the vertices of a triangular grid. Cells located more
ventrally in the entorhinal cortex have larger spacing between firing
fields than those in the dorsal entorhinal cortex. We now know that
the grid cells located in layer 2 also show the phase precession
effect. In a recent computational model, Neil Burgess, Caswell Barry
and I have proposed a modification of the dual oscillator interference
model which accounts for the firing patterns observed in grid cells.
One feature of the model has already been tested and supported. This
is that the resonant frequency of the intrinsic oscillator within the
EC layer 2 stellate cells should vary systematically from dorsal to
ventral entorhinal cortex in order to account for the change in scale
of the grid size in that dimension. This has now been demonstrated by
Hasselmo's group who have also shown that the time constants of the H
current vary systematically from dorsal to ventral in a way which
would explain the changes in natural frequency.