The transition between the 6-layered neocortex and the 3-layered hippocampus is formed by a group of cortical regions collectively referred to as the retrohippocampal cortiecs. The retrohippocampal region consists (in our terminology) of the entorhinal cortex, parasubiculum, presubiculum and subiculum. The entorhinal cortex is nearest the neocortex in its structure and the subiculum is nearest the structure of Ammon's horn.
The entorhinal cortex is the principal cortical input to the hippocampus. It is recognized as the beginning of the "trisynaptic path" This pathway illustrates an interesting organizational feature of the hippocampus. It is an essentially unidirectional loop of excitatory neurons. The layer II projection cells of entorhinal cortex end on dentate granule cells. The granule cell inputs to CA3 form synapse #2. CA3 projections to CA1 form synapse #3. From here, the relay continues with CA1 inputs to subiculum. Subiculum projects into the deep layers of entorhinal cortex and ascending projections from deep cells onto superficial layer cells in entorhinal cortex complete one circuit.
Many other circuits have been described. The interactions between retrohippocampal regions have received little experimental attention. In our efforts to define the cells and basic connectivity of the retrohippocampal regions, we have shown a functional separation of the subicular outflow and different intra-regional and inter-regional circuits.
One of the functional aspects of our work has to do with a large normally-occurring synchronous population event known as the sharp wave. We have developed an in vitro model of the sharp wave complete with its tail of associated gamma-frequency oscillations. We are exploring the cellular and network basis for gamma activity in the retrohippocampal regions. The activity in our model appears to be different from what has been reported in hippocampus or neocortex. We have cells with intrinsic oscillations and GABAergic modulation of this activity. The advantages of this in vitro model of the sharp wave include that it is generated in normal media, the onset and offset of the gamma oscillations are reproducible, intracellular recording techniques can be easily applied, and pharmacological techniques are also easy to apply.
Another functional aspect of our work is the generation of seizure activity. Area CA3 of the hippocampus is one region that can initiate seizure activity. Entorhinal cortex is another. The capabilities of the other hippocampal and retrohippocampal regions are much more limited, but the inter-regional connectivity provides multiple access points for events generated in entorhinal cortex. We are investigating the mechanisms by which individual regions initiate seizure activity and the mechanisms by which such activity invades neighboring regions.
A third functional aspect of our work is the interaction of cortical inputs in each region. This relates most directly to the circuitry underlying navigational behavior. Some hippocampal formation neurons have firing correlates that appear to be almost exclusively locational (e.g. the "p" cells of Ammon's horn). Other cells have firing correlates that appear to be almost exclusively directional ("head-direction" cells of dorsal presubiculum). Projections from these cells can converge directly on other cells (e.g. the pyramidal cells of subiculum) and indirectly, via longer relays, on other cells (e.g. deep layer retrohippocampal neurons). We are studying the combined effects of inputs such as the examples given on identified cells throughout the retrohippocampal regions.
Selected Publications
Funahashi, M., and Stewart, M. (1998). Properties of gamma-frequency oscillations initiated by propagating population bursts in retrohippocampal regions of rat brain slices. J. Physiol. 510, 191-208.
Harris, E., Witter, M. P., Weinstein, G. and Stewart, M. Intrinsic connectivity of the rat subiculum. I. Dendritic morphology and patterns of axonal arborization by pyramidal neurons. Journal of Comparative Neurology 436, 490-505.
Harris, E. and Stewart, M. Intrinsic connectivity of the rat subiculum. (2001). II. Properties of synchronous spontaneous activity and a demonstration of multiple generator regions. J. Comp. Neurol. 436, 506-518, 2001.
Kunitake, A., Kunitake, T., and Stewart, M. (2004). Differential modulation by carbachol of four separate excitatory afferent systems to the rat subiculum in vitro. Hippocampus 14, 986-999.
Saito, T., Sakamoto, K., Koizumi, K., and Stewart, M. (2006). Repeatable focal seizure suppression: a rat preparation to study consequences of seizure activity based on urethane anesthesia and reversible carotid artery occlusion. J. Neurosci. Meth., in press.
List of Publications (Pub Med)
Personnel
Elana Harris, M.D. Ph.D. Student
Rena Orman, Graduate Student