saggital section of rat brain from Jim's lab The Hippocampus
(last updated June 2007 )
A page from: Eric Hargreaves'Page O'Neuroplasticity

The hippocampus is one of the brain structures making up the limbic system. Although the hippocampus lies beneath the cerebral cortex it is not truly a subcortical structure in that it is really a cortical infolding itself, albeit much older and more primitive than the surrounding neocortex. Hence, it is also referred to as archicortex, or paleocortex. Further, the older and therefore also simpler paleocortex of the hippocampus is composed of only three layers, which can be contrasted to the much more entangled six layers of the neocortex, but more on that later. The hippocampus is so named since early on its appearance was likened to a "seahorse", and thus was dubbed the latin equivalent. Personally, I think the early neuroanatomists spent too much time dissecting brains and not enough time on the beach looking at seahorses among the other flora and fauna of beach life worth looking at.

Regardless, Jim Ranck Jr. of the Downstate SUNY group, once gave me the article outlining the historical delineation of the structure's name (ref). Jim also used to greet anyone new to the hippocampal group at SUNY within the first couple of weeks, and present them with a real honest to God dried seahorse, of which I still have mine. Hmm... ...maybe a little too much digression here, so back to the topic at hand.

The importance of the hippocampus to the neuroplasticity phenomena discussed in the articles presented here is that most of the phenomena were originally discovered in the hippocampus. The hippocampus still remains the structure of choice in which to study many of these same pheomena. As such, an oft neglected but important step to understanding hippocampal neuroplasticity is to understand hippocampal anatomy and that of the surrounding cortices and other structures providing the major aferents/efferents (inout/output) of the system.

Basic Anatomy

The rat brain and Hippocampus At left is a depiction of a rat brain with the hippocampus, fornix, and mammillary bodies highlighted in mauve tones, which is based upon figure 1 of Amaral and Witter (1989). The hippocampal formation is a bi-lateral limbic structure which, in overall shape resembles two "Cs" leaning together at the top and spread apart at the base. The top portion of the formation is known as the "dorsal hippocampus" and because of its proximity to the septum, a structure at the midline of the brain, the dorsal tip of the hippocampus is called the "septal pole"
(Amaral and Witter, 1989; Witter, 1989). The rat Hippocampus and fornix

The course of each hippocampus follows the medial aspects of the ventral floor of the lateral ventricle, ending at the bottom tip or "temporal pole". The internal structure of the hippocampus is the same throughout its length, and consists of an infolded convolution of the evolutionarily older and more simple (fewer cell layers), archicortex or allocortex, as contrasted above to the six-layered neocortex. The rat Hippocampus coronal slice

A cross-section taken perpendicular to the long axis (septal-temporal) will reveal the internal structure as two interlocking "Cs", one reversed in relation to the other, each with its own principle cell layer. One "C" makes up Ammon's Horn or Cornu Ammonis (CA1-CA3), also known as the "Hippocampus proper". The principle cell layer of Ammon's Horn is the stratum pyramidale, or the pyramidal cell layer. The other "C" is made up of the Dentate Gyrus, of which the stratum granulosm, or granule cell layer is the principle cell layer. Although the dentate gyrus is commonly included as part of the Hippocampus, it is cytoarchitectonically distinct from the hippocampus proper (the structure of the cells, or their architecture is different; Amaral 1978; Bayer, 1985; Amaral and Witter, 1989; Witter, 1989). However, sometimes the hilus of the dentate gyrus, the area inside the C created by the granule cells is referred to as CA4, as though it belonged to the hippocampus proper. The hilar region is referred to as CA4 because the pyramidal cell layer of the CA1-CA3 regions begins to breakdown as a tightly packed cell layer and becomes more spread out and sparse, or more of a polymorph layer, in this region. Consequently, early neuroanatomists did not distinguish between these areas. Since the dentate gyrus is not truly part of the hippocampus, terms like "Hippocampal formation" are used to discuss Ammon's Horn and the dentate gyrus together. The intrinsic connections between the principle cell layers of the dentate gyrus and CA regions of the hippocampus are very clear. The intrinsic connections were so clear, in fact, that Ramon y Cajal was able to determine the major direction of afferent connections or synaptic flow of the "trisynaptic circuit" through the examination of Golgi stained normal material by itself, as early as 1911 (Andersen, 1975).

Trisynaptic Circuit

Trisynaptic Circuit The hippocampus, when cut transverse to its longitudinal (septal-temporal) axis, exibits a strong afferent set of three connected pathways known as the "trisynaptic" circuit or loop ( Andersen, Holmqvist, and Voorhoeve, 1966; Swanson 1978; 1982; Witter, 1989). First, layers II and III or the "surface layers" of the entorhinal cortex project to the granule cells of the dentate-gyrus, via the perforant-path. Second, the granule cells of the dentate gyrus project to the large pyramidal cells of Cornu Amonnis or Ammon's horn, subfield 3 (CA3), via the mossy fibres system. Third and finally, the CA3 pyramidal cells project to the pyramidal cells of the CA1 subfield, via the Schaffer collateral system ( Lorente de No, 1934; Blackstad, 1956; 1958; Amaral 1978 Bayer, 1985 Amaral and Witter, 1989 Witter, 1989). However, in the last decade, more emphasis has been placed on the associational fibres that connect the transverse circuitry (septal-temporal axis), and thus, more emphasis on the integrated three-dimensional functioning of the hippocampus as a whole (Amaral and Witter, 1989 Witter, 1989).

As more is understood about the overall functioning of the hippocampus, terms like "hippocampal system" come into play, based on the hippocampus, the dentate gyrus, and the adjacent subicular, entorhinal and perirhinal cortices that form the major afferents and efferents to the system. The idea of the hippocampal system being that the adjacent cortices provide a number of diverse and/or related signals, upon which the hippocampus, at the core of the system, performs some unique set of computations transforming, binding or synthesizing the signals into something new that is then returned to different aspects of the same adjacent cortices.

Hippocampal Anatomy: An Historical Overview

From the above discussion it can be seen that delineating the boundaries of what is, and what is not the hippocampus plays only a small part of anatomy research and that much of the work deals with the mapping of the pathways like Ramon Y Cajal's description of the afferent flow a century ago. As such, the bulk of anatomical research identifies what projects to what, and what the projections use to get there. As elegant as Ramon Y Cajal's description of the afferent flow of the hippocampus was 100 years ago, the hippocampal system in its entirety is far more complex, subtle, and differentially distributed than the much simplified "connect-the-dots" of the tri-synaptic circuit.

To understand all the work that has been done, it is helpful to see the anatomical results through a historical framework founded on the development and advances in histological staining. These advances in techniques have tended to develop along two directions; first, revealing greater isolation of individual and later specific neurons and second, revealing greater distances along pathways between neural connections. Knowing the techniques that came into play at what time and what each revealed, better enables us to understand hippocampal anatomy, and thus the hippocampus itself. Although this section focuses on staining techniques, it must also be noted that advances in the technology of light microscopy had also just barely been completed in the first half of the nineteenth century, with great improvements in the optics of compound microscopes, such as the condenser system (Zeiss and Abbe, 1873) and thin slice microtome (Willhem His, 1866) and its refinement (Minot, 1886).

The histological stains of the times, much like today, dyed different cell organelles and not entire cells. Also the stains were often literally dyes for clothes, like Carl Weigert's borrowing of hematoxylin (1885), which stained the nuclei of cell bodies a deep blue-violet. Lifted from the textile industry, Hematoxylin came from the logwood tree of Central America and was originally brought over by the conquistatdors as a clothing dye (Titford, 2005). Similarly, Carmine, another clothes and cosmetics dye, derived from the ground up bodies of cochineal insects also brought over from Central America, produces a vibrantly enduring crimson stain (think of flaming red lipstick). Although stains such as these give an indication of the size and packing density of the cells and cell layers, they could not distinguish between the various "protoplasmic processes" identified earlier, or trace their full extent (Cimino, 2000).

Camillo Golgi

Silver Nitrate Impregnation, Camillo Golgi (1843-1926)

The histological technique to provide the first big advance in hippocampal anatomy was the Golgi method. Initially developed by the Italian physician Camillo Golgi, who published his first work in 1873 using "la reazione nera" or "the black reaction" (Jones, 1999). The Golgi method was not so much a staining technique as it was a means of impregnating a limited number of neurons, possibly as low as 1/100 with silver nitrate, such that the entire extent of the cell was rendered opaque and highly visble in all its exsquisite detail. This was very different from the staining of the time, which as mentioned above could not penetrate the full protoplasmic extent of the cells, thereby typically only revealing the cell bodies, and their immediate projections. In contrast, the Golgi impregnation, could outline in beautiful detail all of the "protoplasmic processes" later to become Wilhelm His' dendrites (1881) and Kolliker's axon (1896). Additionally, from the Golgi impregnation one could identify the shape of the cell, and therefore its orientation, and of course the full extent of the dentritic arborization.

Golgi's hippocampus Golgi's lone work on the hippocampus in 1883 was the first to use the silver nitrate impregnation revealing such great detail. At right is one Golgi's schematic drawings summarizing the structure of the hippocampus taken from his collected works or "Opera Omnia" of 1903, which included the original pes Hippocampi major of 1883 (Swanson, 1999). Although a fairly accurate representation of what we think of the hippocampus today, one can note that while the apical dendrites of the pyramidal system end freely, the basal dendrites in the stratum oriens fuse together into a tightly woven web. Golgi, from his observations, incorrectly assigned the apical dendrites a nutritive role, taking sustenance from the glia and vasculature, he presumed they encapsulated. As a reticularist, Golgi further incorrectly argued that the basal dentrites formed part of the continuously connected neural reticulum or finely wrought web. Yet, by functionally differentiating between the apical and basal dentritic systems, Golgi had begun to set himself apart from the earlier reticularists, and had begun to lay the groundwork for the Neuron Doctrine. Along with settling on a standard terminology for the hippocampus' lamination, Golgi's other lasting contribution to the hippocampus was at the gross level, where he was the first to argue that Ammon's horn was separate from the fascia dentata or dentate gyrus (Swanson, 1999). Despite the errors stemming from his theoretical viewpoint, Golgi was awarded the Nobel prize for medicine in 1906, along with Cajal.

1930s portrait Santiago Ramón y Cajal

Santiago Ramón y Cajal (1852-1934)

Cajal slides Golgi Stained Human cerebellum labelled bbb for bueno, indicating quality Although developed by Camillo Golgi, it was in the hands of Santiago Ramón y Cajal that "la reazione nera" flourished. Cajal, similar to the small number of his contemporaries, who were beginning to employ the black reaction, modified the technique to his advantage, by re-impregnating the samples a second time, a double-dipping so to speak. The next two figs are why I remain amazed at what can be found on the web. First up is an actual slide of Cajal's, complete with his handwritten labels, identifying the slide as "bueno, bueno, bueno", for its good quality.

Photomicrograph from one of Cajal's Golgi preparations, a Pryamidal cell in the cerebral cortex This is followed by an even more amazing pic, a modern photomicrograph taken of a small segment of one of Cajal's original Golgi slides. How cool is that? Here, one is literally peering in at a small segment of history that has had major implications for where Neuroscience is today. Even though the slide is over a century old, for its clarity, the photomicrograph may have been taken of a specimen stained and coverslipped within less than a week. The segment itself depicts a single, but well outlined (as though in Chinese ink), pyramidal cell from the cerebral cortex.

In the latter half of the 19th century, although cells were accepted as the basic unit for the rest of the body (Virchow, 1855), the nervous system was considered by many to be a finely wrought mesh of continuously connected fibres or "reticulum", the proponents of which included Camillo Golgi.

Cajal's hippocampus Cajal and the likes of Kolliker and His, began publishing evidence to the contrary, culminating in the Neuron Doctrine and establishing modern Neuroscience. Cajal and the handful of his contemporaries were successful due in part to the fact that they studied not just mature human tissue, but ontologically earlier specimens from immature or embryological samples, where neurons could be examined at different stages of development. Cajal and his contemporaries also tended to study simple and clearly laminated (layered) structures , such as the retina, cerebellum, and hippocampus. These approaches combined with the new and sparsely staining Golgi technique allowed the previously complex web of interconnected reticulum to be reduced to its constituent components. Where before a tangled forest stood blocking the view, now stood, but a few well-defined trees.

In 1906 Cajal, along with Golgi were awarded the Nobel Prize in Medicine for their contributions to the advancement of "Neurology"; Golgi for his silver impregnation technique, and Cajal for his tremendous use of the technique. Of course still on opposite sides of the Neuron/Reticulum debate, Golgi's acceptance speech was an attack on the Neuron Doctrine, while the next evening's acceptance speech by Cajal was summary of evidence in favour of the Neuron Doctrine.

Cajal turned to the hippocampus, as one of several subjects, during the course of the early 1890s, as the Neuron Doctrine was first becoming established. Initially presented in individual papers, the hippocampal work was best summarized in Cajal's opus magnum "Textura del Sistema Nervioso del Hombre y los Vertebrados" the first volume of which was published in 1899, with the second being published in 1904. Unfortunately much of this remained inaccessible to the scientific community at large until translated into French as "Histologie du Système Nerveux de l'Homme et des Vertébrés" in 1909 and re-published as a 2nd edition in 1911, with some additional figures from Cajal. Of course I had to wait for Neely and Larry Swanson's 1995 english translation before I could actually read the chapters, insterad of merely gazing at the pretty drawings. Since then, I've come to appreciate a more literal translation, and beautiful reproduction of the figures in Pedro and Tauba Pasiks 1999 (for Volumes I & II) and 2001 (for Volume III) translation.

From these chapters Cajal described in detail the cytoarchitecture or cells and cellular components that populated the lamina defined earlier by Golgi and others (alveus, oriens, pyramidale, rediatum, lacunosum moleculare). He also provided an ontological framework for the development of the various laminar components, with a cross species comparison. Finally, Cajal introduced two divisions for Ammon's horn or hippocampus proper based on the presence or absence of recurrent circuitry of the pyramidal cell layer (Cajal, 1904), which eventually was surpassed by the nomenclature of Cajal's final and most influental student: Rafael Lorente de Nó.

A young Raphael Lorente de Nó

Rafael Lorente de Nó (1902-1990)

A precocious medical student in Zaragoza, first published at age 15, Raphael Lorente de Nó became fascinated with the nervous system. Lorente de Nó quickly exhausted the knowledge of his immediate mentor Professor Pedro Ramon, who had in turn learned from his older brother Santiago. As such, in 1920, Pedro passed his eager 18 year old student on to the great Cajal then 68 years old himself in Madrid (Kruger and Woolsey, 1990). There, already proficient in the Golgi technique Lorente de Nó set about intentionally disproving an early Cajal idea. Previously Cajal had suggested in passing that the strength of human intellect over other animals, may lie in the number and complexity of morphological cell types in the nervous system. Lorente de Nó using the Golgi technique examined the mouse cortex, considered at the time, to be the lowest animal with a neocortex. The neuronal patterns that Lorente de Nó found and described in the primary auditory cortex were at least as complex as those observed in humans. Subsequently, in a move that says as much about master, as it does about the pupil, Cajal had the work published in his own journal. Although proofed, Cajal left the manuscript largely unaltered and untouched by his own hand, published, written as it was, by Lorente de Nó, (Lorente de Nó, 1922).

more to come...

To quickly list succession of techniques would be to start with the Golgi techniqe of silver imgregnation, later to become Golgi-Cox gold impregnation, followed by Fink Heimer silver degeneration for tracing, followed by fluorescing aldehydes under ultra violet light, to identify the amine transmitter systems (indole amines and xx amines noradrenaline (epinephrine if you're a Brit), dopamine and serotonin) and immuno-fluorescing essentially the same, but generating sizeable antibody reactions that fluoresced, followed by autoradiographic lighting, followed by specific and unique stains such as lucifer yellow diamon blue. etc.

More Anatomy than you ever wanted to know

Coming soon...


H.M.

In the early 1950s a young man suffering from intractable epilepsy underwent a bilateral resection of the medial temporal lobes at the hands of William Beecher Scoville, a prominent nerusosurgeon at the Hartford Hospital, Connecticut. The resection included a large removal of the hippocampus the amygdalae and the overlying cortex. Ultimately successful in reducing the seizures, the surgical resection however, left the young man with a florid and profound anterograde amnesia that persists to this day some 6 decades later. The famous case of H.M. ushered in the modern era of brain research on learning and memory.

First reported by Scoville (1954) as 1 of 2 cases out of 230 that developed memory problems after this surgery, the case of H.M. did not have its full impact until Scoville and Milner (1957) found evidence of amnesia in 8 of the testable pyschotics, who had also received this operation by Scoville. Scoville and Milner (1957) attributed H.M.'s severe amnesia to the removal of both hippocampi and amygdali (Milner, 1972; Corkin, 1984).

Hippocampus and memory

The now famous case of H.M. has had a major influence in the field of memory, focusing much of the work since, on the structure and function of the hippocampus. Since that time, the amount or research that has gone into determining the role of the hippocampus in learning and memory processes, if any at all, has filled many books (The Hippocampus as a Cognitive Map, 1978; The Hippocampus Vols. I & II 1975; III & IV 1986; The Neurobiology of The Hippocampus, 1983 The Hippocampus - New Vistas, 1989 Functions of the Septo-Hippocampal System, 1978), and countless articles, and continues to do so...

At first, the hippocampus was promoted as an all encompassing learning structure. However, it soon became clear that H.M.'s motor learning ability appeared to be intact, although he had no recollection of ever performing the tasks when tested in repeated sessions (Corkin, 1965; 1968; Cohen and Corkin, 1981). The cerebellum, a brain structure involved in the smoothing of motor movements was, at that time, being argued as the critical learning centre for classically conditioned motor responses (for a review at the time see Thompson, et al., 1983). Thus, the cerebellum became the potential source of H.M.'s motor learning ability, and relegated the hippocampus to one of at least two learning structures. Of course, the hippocampus still held preminance as the structure responsible for conscious learning, an idea was reinforced by the report of a stroke case, in which damage restricted to the CA1 subfield of the hippocampus, resulted in amnesia (Zola-Morgan, Squire, and Amaral, 1986; but see Horel, 1994).

However other clinical cases, in which portions of the hippocampus were destroyed for relief from intractable pain (Gol and Faibish, 1967), or destroyed to reduce seizures (Glaser, 1980) did not necessarily result in amnesia, and a growing body of evidence from animal research indicated that lesions restricted to the hippocampus were unable to produce the global, florid amnesia expressed by H.M. As a result, much paring down has occurred during the last few years regarding the role of the hippocampus in learning and memory processes (Zola-Morgan et al., 1989a; 1989b; Meunier et al., 1993).

Currently, it appears that the hippocampus is part of a larger learning system or systems, and with hindsight it is more than likely that the severe, global amnesia of H.M. is caused by the bilateral removal of the hippocampus, amygdala, in concert with additional damage to the cortical areas overlying the hippocampus (Horel, 1994; Petri and Mishkin, 1994). Consequently, ideas of the hippocampus have evolved to become ideas about the hippocampal system, which anatomically, now encompasses the overlying cortices feeding into the hippocampus (entorhinal, perirhinal, and parahippocampal), and encompasses, as hippocampal projection sites, subicular, infralimbic and other prefrontal cortical areas (Petri and Mishkin, 1994 Horel, 1994; Cohen and Eichenbaum, 1993). How much of the front end, and how much of the back end is included in the hippocampal system depends upon whose conception of the hippocampal system is being discussed, with some not wishing to label it as the hippocampal system at all (Horel, 1994).

Additionally, the hippocampus may work in parallel, interact, or compete with other forebrain learning systems (Packard et al., 1989; McDonald and White, 1995a; 1995b; White and McDonald, 1993a; 1993b). Further, ideas about the hippocampus itself are also becoming internally more modular, or heterogenous, such that the different regions or subfields may participate in different computational functions (Cohen and Eichenbaum, 1993). Finally, the whole idea of the hippocampus' involvement in learning and memory has been called into question (Vanderwolf and Cain, 1994). Yet, despite the ongoing debate, most researchers believe that the hippocampus, or hippocampal system has some role to play in learning and memory processes.

Theories of Hippocampal Learning and Memory Function

Even if most researchers consider the hippocampus to be involved in learning and memory, exactly how it is involved, and the extent of its involvement is another debate altogether. So it should not be too surprising to discover that a number of distinct theories of hippocampal function exist, and often are born out of task-specific and species specific research. For example, the "two factor" learning and memory theories, such as David Olton's (1977) working/reference memory systems were born out of radial maze work with rats, whereas the Declarative/non-declarative memory system was largely generated by nonhuman primate work with DMS/DNMS tasks. Additionally the rodent literature (with some degree of lip-service paid to human and nonhuman primate work) has generated the...
Cognitive Map Theory (O'Keefe and Nadel (1978);Hippocampus Forum, 1991; various authors).
Configural Association Theory (Sutherland & Rudy, 1989; Rudy & Sutherland, 1989; 1995)
...and the newest (or most recently updated) versions of
Path-integration (Gothard, et al., 1996, Knierim et al., 1996, McNaughton et al., 1996, Whishaw, Cassel & Jarrad, 1995, Whishaw & Jarrad, 1996, Whishaw, McKenna & Maaswinkel, 1997).
Finally, there have been a number of attempts to produce encompassing theories of hippocampal function that take into account the human lesion literature, the experimental lesion literature, and hippocampal electrophysiology (Cohen and Eichenbaum, 1993).

Hippocampus Sensitive Tasks

Although animal models of learning deficits using hippocampal lesions have been unable to generate the global learning impairment exhibited by H.M., hippocampally lesioned animals have shown consistent impairment in a number of tasks. Often these tasks are also impaired by lesions to areas other than the hippocampus, but it is worth noting that these areas typically either feed into the hippocampus or feed from the hippocampus.

Delayed non-matching to sample (DNMS)

Delayed non-matching to sample (DNMS) is one of the nonhuman primate tasks that exhibits deficits after surgical removal of portions of the medial temporal region that mimic H.M.'s excision. A variety of object memory tasks were created based on the "Wisconsin Testing Apparatus", in which objects hidden by a horizontal shutter are presented to the test subject for a set time by raising the shutter, followed by an imposed retention delay with the shutter down, and completed when the shutter is raised again and the subject selects an object. In the DNMS version of the task, two objects are presented to the subject, of which one is rewarded, after a delay the previously rewarded object is paired with a new object and the subject has to select the new object in order to obtain the next reward.

Data from this task was one of the stronger lines of evidence in favour of a relatively exclusive hippocampal role in certain memory processes (Mishkin, 1978; Zola-Morgan, Squire, Mishkin, 1982; Zola-Morgan and Squire, 1985). Arguments, against the specific hippocampal hypothesis, in favour of the cortical areas overlying the hippocampus go back as far as 1978 (Horel, 1978). Currently it appears that these criticisms were appropriate, and that the hippocampus itself may not be as critical, or even necessary, as previously believed (Horel, 1994; Zola-Morgan et al., 1989a; 1989b; Meunier et al., 1993).

Radial-arm maze

The radial-arm maze developed by Olton and Samuelson (1976), was one of the first maze tasks that attempted to test memory of locations, instead of testing memory of routes (Olton, 1977). In its original form, eight-arms projected out radially from a central location. On a single trial the end of each arm was baited with a small food reward and rats were placed in the centre of the maze and allowed to enter the different arms repeatedly until all the food was consumed. Rats soon learned that the optimal strategy for obtaining all the food with the least amount of effort was to visit each arm only once during a trial. Arms that were re-entered after being cleared of food were scored as errors, and increased the time required to complete the maze (Olton, 1977). Thus, Olton suggested that the radial-arm maze tested "spatial-working memory". Working memory being the short term store or register that allowed rats to keep track of which arms they visited on a given trial. This information would only have to be stored for a short time (the duration of the trial), since remembering arms entered on previous trials would interfere with keeping track of the current trial.

Matthew Shapiro's radial-arm maze at McGill Olton also developed variants of the 8 arm radial maze, which allowed reference memory (RM) to be tested in addition to working memory (WM). To test both RM and WM, only 4 of the 8 arms were consistently baited with food reward. To perform the 4/8 task optimally, each baited arm should be entered only once each trial, and the unbaited arms never entered. Reference memory in this task required diferentiating the locations of the baited arms from those of the unbaited arms across all trials, as a long term rule, whereas WM, still required the cumulative temporary memory for the locations of all the baited arms a specific trial (Olton, et al., 1979). To place an additional load on WM, and forego testing RM the 8/8 radial task is used and is simply the original version where all 8 arms are baited (Olton & Sammuelson, 1976). Additionally, reterograde and anterograde WM can be tested by imposing a delay after a number of initial choices have been made, with the final choices being executed after the imposed delay. Reterograde WM errors are made when arms entered prior to the delay are entered again, while anterograde WM errors are made when arms entered after the delay are entered again (Olton, 1983). The original maze was simply a set of arms radiating out from the central platform, with all the arms always open. In order to run the delayed WM/RM 4/8 protocols, ways of restricting the rats to the central location were devised. Pictured at right was the maze in Matthew Shapiro's lab when he was at McGill. A series of Plexiglass guillotine doors kept the rats in the center. This was a standard solution for many homemade mazes, other commercial designs employed short drawbridges or actually involved mechanically folding down the whole arm.

Regardless of the actual apparatus, rats with lesions to the hippocampal system result in their inability to perform the radial-arm maze without errors (Olton, 1983; Olton, Becker, & Handelmann, 1979; Olton & Papas, 1979). Pretraining prior to receiving hippocampal lesions selectively disrupts WM, but not RM. If a delay is imposed more reterograde WM errors than anterograde WM errors will be generated (Olton et al., 1979; Olton, 1983).

Water maze

The water maze, or "Morris water maze" (1981) was developed as a specific alternate to the radial maze and the ideas of spatial "working memory" and "reference memory" developed by David Olton (Olton & Sammuelson, 1976; Olton, 1977).

Matthew's water-maze at McGill In the water maze's most simple form, animals are released from one of four cardinal points around a circular pool, filled with water and made opaque by a material such as powdered milk, and expected to find the hidden platform submerged just beneath the surface. Over a number of trials animals learn the location of the hidden platform based on distal cues not directly associated with the platform and their times to locate to platform decrease. Strength of learning is tested afterwards by a probe trial, in which the hidden platform is removed and the amount of time spent in the former region of the platform, is measured as the strength of the learning (Morris, 1981; Sutherland & Dyck, 1982). As a control task, the water-maze is run with the platform raised above the surface, such that it is clearly visible. This version does not require the rats to remember anything of the location of the platform, but ensures that the animals can swim well enough to navigate their way to the platform. The Morris water-maze task claims to assess spatial navigation and learning, and had the advantage over the radial maze of being able to demonstrate the ability of rodents to locate a place without visual, auditory or olfactory cues available as guiding strategies. Pictured at right is the watermaze used in Matthew Shapiro's lab when he was at McGill. As watermazes go it was a pretty standard size at 1.5m diameter, although the earliest water maze in Richard Morris' lab was only 1m in diameter and later watermazes in the same lab grew to be 2m.

Initial acquisition has been found to be sensitive to hippocampal lesions (Morris et al., 1982; Sutherland, Whishaw and Kolb, 1982), and selective lesions of the dentate gyrus (Sutherland, Whishaw and Kolb, 1983).

Acquisition is also disrupted by lesions downstream of the hippocampus, in the subicular complex (Morris, Schenck, Tweedie and Jarrard, 1990) and medial frontal cortical region (Sutherland, Whishaw and Kolb, 1982). Lesions upstream of the hippocampus such as the perforant path, the main entorhinal input to the hippocampus (Skelton and McNamara, 1992) and lesions to the medial septum, the other major input to the hippocampus (Hagan et al., 1988) also disrupt acquisition.

Additionally, as indicated above, the hippocampal system may also interact or run in parallel with other forebrain learning systems to solve certain aspects or variants of the water maze (McDonald and White, 1994; Devan, Goad, and Petri, inpress).

Finally, somewhat like DNMS, the hippocampus' role in the traditional aspects of the water maze has also come into question. Whishaw et al. (1995) have shown that with extensive visible platform training, in which the distance to the platform was gradually increased, rats with fimbria/fornix lesions (disconnected hippocampi) exhibited a degree of spatial learning by heading for the hidden platform from distal sites. Yet subsequently, when the platform was switched to a new location, the fimbria/fornix lesioned animals could not learn its new position, even after many trials. Whishaw et al. (1995) use these data to argue that a further distinction may be required in the water maze between discovering the appropriate strategy "getting there" in addition to the more traditional "knowing where", and that hippocamnpally lesioned animals are impaired on the former, but not the latter. However, Devan et al. (inpress) suggest that other forebrain learning systems, particularly in the striatum, may be allowing the hippocampally lesioned animals to solve the first platform location in a non-spatial manner, albeit, not as successfully as had the hippocampus been intact.

It is more than likely that traditional water maze protocols will give way to more advanced protocols that can tease apart the specific aspects currently being debated. Similarly, simple escape latency measures will more than likely give way to more advanced pattern detection measures.

Hippocampus References...

Amaral, D.G. (1978). A golgi study of cell types in the hilar region of the hippocampus in the rat. Journal of Comparative Neurology, 182, 851-914.

Amaral, D.G. & Witter, M.P. (1989). The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience, 31, 571-591.

Andersen, P. (1975). Organization of hippocampal neurons and their interconnections. In R.L. Isaacson & K.H. Pribram (Eds.) The Hippocampus Vol. I (pp. 155-175), New York, Plenum Press.

Bayer, S. (1985). Hippocampal region. In G. Paxinos (Ed.) The Rat Nervous System Vol1; Forebrain and Midbrain (pp. 335-352), New York, Academic Press.

Blackstad, T.W. (1956). Commissural connections of the hippocampal region in the rat, with special reference to their mode of termination. Journal of Comparative Neurology, 105, 417-528.

Blackstad, T.W. (1958). On the termination of some afferents to the hippocampus and fascia dentata. Acta Anatomica, 35 202-214.

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