Brief anatomical overview

Figure 2.22: Preparation of a human hippocampus alongside a sea horse (from Wikimedia, 2010, published under CC-BY-3.0).

The hippocampus derived its name from the Greek wordshippos(horse) andkampos(sea monster) because it resembles the form of a seahorse (cf. Figure 2.22).

The hippocampus is part of the limbic system, and its size generally increase in higher species (Stephan, 1983;

although there are some highly developed species like dolphins and whales which do not follow this law Ja-cobs et al., 1979; Stephan and Manolescu, 1980). For example, the volume is ten times larger in monkeys than in rats, and even hundred times larger in humans.

Nonetheless the basic anatomy is similar in all three species (Andersen et al., 2007), and therefore it is as-sumed that also the general functions (including the

behavioral functions it subserves) are similar. The following description, and also the studies of hippocampal activity described afterwards, refer to rat experiments, because this species has become the main target of experimentalist.

The hippocampus consists of three subregions: The dentate gyrus (DG), the hippocampus proper (HP; subdivided into CA1,CA2 and CA3) and the subiculum (Andersen et al., 2007; van Strien et al., 2009; Cutsuridis et al., 2010, and Figure 2.23).

It has a laminar structure with three main sublayers: The deepest layer contains a mixture of afferent and efferent fibers and interneurons. It is called hillus in the DG and stratum oriens in the CA regions. Superficial to this polymorph layer there is the cell layer that contains principal cells (mainly pyramidal neurons) and interneurons This layer is named granule layer in the DG,

Figure 2.23: Basic anatomy of the hippocampus. (A) Nissl-stained crossection of the hippocam-pal formation and the parahippocamhippocam-pal region in the rat brain (Figure modified from van Strien et al., 2009, with permission). (B,C) The wiring diagram of the hippocampus is traditionally presented as a trisynaptic loop. The major input is carried by axons of the perforant path, which convey polymodal sensory information from neurons in layer II of the entorhinal cortex to the dentate gyrus. Perforant path axons make excitatory synaptic contact with the dendrites of granule cells: axons from the lateral and medial entorhinal cortices innervate the outer and middle third of the dendritic tree, respectively. Granule cells project, through their axons (the mossy fibers), to the proximal apical dendrites of CA3 pyramidal cells which, in turn, project to ipsilateral CA1 pyramidal cells through Schaffer collaterals and to contralateral CA3 and CA1 pyramidal cells through commis-sural connections. In addition to the sequential trisynaptic circuit, there is also a dense associative network interconnecting CA3 cells on the same side. CA3 pyramidal cells are also innervated by a direct input from layer II cells of the entorhinal cortex. The distal apical dendrites of CA1 pyramidal neurons receive a direct input from layer III cells of the entorhinal cortex. There is also substantial modulatory input to hippocampal neurons.

The three major subfields have an elegant laminar organization (see also zoomed view in C) in which the cell bodies of principal cells are tightly packed in an interlocking C-shaped arrangement (granule layer/stratum pyramidale), with afferent fibers terminating on se-lective regions of the dendritic tree. The hippocampus is also home to a rich diversity of inhibitory neurons that are not shown in the figure. Figure and caption modified from Neves et al. (2008) with permission.

and stratium pyramidale in the HP. The most superficial layer is referred to as the molecular layer (stratum moleculare) in the DG and the subiculum; in the HP it can be further subdivided into stratum lucidum (only in CA3), stratum radiatum and stratum lacunosum-moleculare (cf.

zoomed view of CA1 in Figure 2.23C).

The most prominent connection pathways to and within the hippocampus are summarized in Figure 2.23 (for a more complete description see, e.g., Witter and Amaral, 2004; Andersen et al., 2007; van Strien et al., 2009; Cutsuridis et al., 2010): The main input to the hippocampus arises from the entorhinal cortex (EC) via the so called perforant pathway and terminates at the dendrites of granule cells in the DG. These cells project forward via the mossy fibers to the pyramidal neurons in CA3, which in turn project to the CA1 pyramidal neurons via the Shaffer collaterals. This feed-forward projection (EC→DG→CA3→CA1) is referred to as the trisynaptic loop, or in an extended version polysynaptic pathway, where the subsequent projection from CA1 to the subiculum is also considered. In fact the projection from CA1 to the subiculum has turned out to be even more prominent than the CA1→EC projection, the classical termination of the trisynaptic loop (Andersen et al., 2007; Cenquizca and Swanson, 2007; van Strien et al., 2009).

The output from the hippocampus formation arises (mainly) from CA1 and subiculum and targets, in particular, the deeper layers of the entorhinal cortex.

Besides this feed-forward pathway, recurrent connections within the areas of the hippocampus, and back projections (i.e., in the reverse direction of the polysynaptic pathway) have been described (reviewed in, e.g., Witter and Amaral, 2004; Andersen et al., 2007; van Strien et al., 2009). Recurrent connection (also referred to as associational projections) are most prominent in area CA3, but they are also found — although less prominent — in the other regions of the hippocampal formation (Witter and Amaral, 2004; van Strien et al., 2009, and references therein).

In Chapter 7 we consider the representation of spatial information (location) by the principal cells, i.e., the pyramidal neurons, in area CA1 and CA3. These cells (cell bodies) are placed in the stratum pyramidale, with the basal dendritic tree located in the stratum oriens and the apical tree extending to the superficial layers (cf. Figure 2.13 and 2.23C). The pyramidal cells are surrounded by a very heterogeneous group of GABAergic interneurons (at least 12 types of interneurons differing in single cell properties, formation and extent of axonal and dendritic trees have been reported so far, Witter and Amaral, 2004; Klausberger, 2009). These interneurons form mainly (but not exclusively) local recurrent connections to both the soma (in particular the axonal initial segment) and the dendrites of the pyramidal neurons, and therefore provide a feed-back loop which dampens excitatory input, but might be also involved in dendritic computation (see Section 2.2).

More information about the anatomy and the properties of single cells can be found in textbooks and review articles (e.g., Paxinos, 2004; Duvernoy, 2005; Andersen et al., 2007; van Strien et al., 2009; Klausberger, 2009; Cutsuridis et al., 2010)