Dorsoventral vs. Septotemporal hippocampus

Everybody knows what the hippocampus is for: memory. And…maybe something about anxiety or depression? Yes – over the last 10 years or so many studies have been published showing that the hippocampus has these two roles and that the mnemonic and emotional functions of the hippocampus are associated with its septal (dorsal) and temporal (ventral) ends, respectively. This new knowledge means that we’ve had to reorient our perspective. What we see when we consider the septal hippocampus may not be the same if we only consider its temporal end. My goal here is not to provide a review of the memory vs. emotional functions of the hippocampus (btw this dichotomy is a vast oversimplification). Instead, I’d like to talk about how people have differentiated these two ends of the hippocampus in their analyses. I’m also happy to showcase a bunch of pretty anatomical images that will probably never be published in a traditional journal article.

Some studies showing different functions of septal and temporal hippocampus

  • Some of the best reviews of the topic are by Bannerman et al from 2004 and 2011.
  • A recent and free review article by Fanselow and Dong.
  • Classic Moser papers showing spatial memory is more dependent on dorsal hippocampus and anxiety/fear behavior on ventral hippocampus
  • A recent paper suggesting that spatial processing in the septal hippocampus meets the behavioral-control functions of the temporal hippocampus to enable rapid spatial learning

History of neurogenesis quantification. So, back in the day, before I even knew what a neuron was, and before it was well-established that there was functional differentiation along the hippocampal axis, people would pick a few sections from the dorsal hippocampus (it’s much more photogenic, gets all the glory), count new neurons, and make it a density measurement. Then the stereology police arrived (seriously, that’s what they’re called) and pointed out that changes in tissue volume or cell packing could change density measurements without there being any differences in numbers of cells. Stereological analyses also prevent any biases that might arise from creating arbitrary boundaries when examining only part of the hippocampus. And so people started doing stereological counts, which require a systematic quantification throughout the entire hippocampus. My guess is that this probably delayed the appreciation that neurogenesis could vary in magnitude and function along the hippocampal axis. Now that we know that stereology is pointless we can get back to business (this is a joke – please don’t arrest me).

Difficulty of quantifying subregions due to curvature of the hippocampus. One of the reasons the hippocampus is such a popular neurobiological model is its anatomy – the dentate gyrus, CA3 and CA1 subfields are all composed of tightly packed cells that are easy to identify. Thinking of the hippocampus along its long axis, one end projects to the septum and the other abuts the temporal lobe, hence “septotemporal” is technically the most accurate way to refer to the different ends of the hippocamus. The hippocampus is curved in such a way that you can actually cut it along any of the 3 spatial planes (X, Y, Z aka coronal, horizontal, sagittal) and hit the hippocampus perpendicular to the septotemporal axis somewhere, giving rise to the classic the trisynaptic circuit. However, because of this same curvature, sectioning the brain in only one of the three planes means that some portion of the hippocampus is not going to be cut perpendicular to the long axis, producing sections in which septotemporal coordinates are hard to define.

The 3D nature of the hippocampus using images from the Allen Brain Explorer:

Dentate Gyrus in 3D 

Figure 1: The dentate gyrus subfield of the hippocampus (i.e. green banana), from its septal pole, extends caudally and laterally and then ventrally. Green axis=dorsoventral, red=rostrocaudal, yellow=mediolateral.



The dentate gyrus is shown in bright green in this relatively caudal section. This section contains ventral dentate gyrus (at the bottom, by "temporal") but, at the top of the section, it also contains a portion of the dentate gyrus that as dorsal as any other part of the dentate gyrus, despite being far from the septal pole.


Figure 2: A relatively caudal coronal section with the 3D dentate gyrus shown in the left panel, for comparison. This section contains ventral dentate gyrus (at the bottom, by “temporal”) but, at the top of the section, it also contains a portion of the dentate gyrus that is very dorsal, despite being far from the septal pole.



This section is even more caudal yet the dentate granule cells (white patches within bright green region) are more dorsal than in the previous section. So, more caudal doesn't necessarily mean more ventral.


Figure 3: This section is more caudal than the previous example, yet the dentate granule cells (white patches within the bright green region) do not extend as far in the ventral direction. So, more caudal ≠ more ventral.


Others on the curvature problem:

Schlessinger et al., 1975: Since the dentate gyrus follows the general curvature of the hippocampal formation, it is difficult to apply the usual topographical terms to its various parts. The rostral third or half of the gyrus is more-or-less horizontally disposed within the cerebral hemisphere…At about the junction of its rostral and caudal halves the gyrus is sharply flexed upon itself, and comes to be vertically disposed….Again, because of the flexure of the hippocampal formation, it is inappropriate to refer to the dentate gyrus as having a dorsal (or rostral) and a ventral (or caudal) part. Following Gottlieb and Cowan (’73) we shall refer to the long axis of the gyrus, extending from the temporal pole of the hemisphere to just behind the septal region, as its temporalseptal axis.
Amaral & Witter, 1989: Because of its complex three-dimensional shape, normal sections of the hippocampus, i.e. those oriented perpendicular to the long axis, are obtained for only a small part of its septotemporal extent in standard coronal or horizontal sections. This situation severely complicates the analysis of the connections within the hippocampal formation.
De Hoz et al., 2003: In discussing different regions of the hippocampus, we use the terms “septal” and “temporal” to refer to the rostralmost and the ventralmost poles of the longitudinal axis, respectively, because this terminology allows an even division of this axis into septal and temporal halves. The terms “dorsal” and “ventral” are sometimes used to refer to the same areas; the dorsal hippocampus is, however, more extensive than the ventral.

So how can we divide the hippocampus? Many people work with coronal sections. Can we delineate boundaries between different hippocampal subregions in coronal sections? Banasr et al. has described a reproducible method for separating dorsal from ventral hippocampus using coronal sections. Here, the dorsal regions would contain a fair bit of mid-septotemporal hippocampus but indeed, only the dorsal sections would contain septal hippocampus and only ventral sections would contain temporal hippocampus:

Banasr dorsal vs ventral


Figure 4: Separating dorsal and ventral hippocampus in coronal sections