Open access peer-reviewed chapter
Abstract
Hippocampus is the region of the brain that is primarily associated with memory. The hippocampus, which is located in the inner (medial) region of the temporal lobe, forms part of the limbic system, which is important in regulating emotional responses. The hippocampus is thought to be principally involved in storing long-term memories and in making those memories resistant to forgetting, though this is a matter of debate. It is also thought to play an important role in spatial processing and navigation. Cholinergic system has implicated in the functionality of hippocampus interconnections with other neurons for efficient memory modulation. Pyramidal and globular cells are the main cells of the cornus ammonis and the dentate gyrus which is essential in relational memory consolidation. Acetylcholine is the main neurotransmitter implicated in encoding of memory in the hippocampus. There are diseases that are associated with hippocampus relational memory such as Alzheimer’s disease which is currently a global challenge. The hippocampus communicates with widespread regions of cortex through a group of highly interconnected brain regions in the medial temporal lobe. There is paucity of data on its role on relational memory. Therefore, the role of hippocampus in relational memory will be elucidated in this chapter.
Keywords
- hippocampus
- relational memory
- cornus ammonis
- acetylcholine
- Alzheimer’s disease
1. Introduction
The hippocampus was first referred to by a Venetian anatomist Julius Caesar Aranzi in 1587. He described it as a ridge along the floor of the temporal horn of the lateral ventricle and likened first to silkworm, and later to a seahorse (Figure 1). In the 1740s, Rene-Jacques Croissant de Garengeot, a Parisian surgeon, coined the term “cornu ammonis,” meaning the horn of Amun, and ancient Egyptian god. The organ is coined from two Greek words “hippo” for horse and “kampos” for sea [1].
Figure 1.
Seahorse-shaped hippocampus.
The hippocampus is the “flash drive” of the human brain and often associated with memory consolidation and decision-making, but it is far more complex in structure and function than a flash drive [2]. The hippocampus is a convex elevation of gray matter tissue within the parahippocampal gyrus inside the inferior temporal horn of the lateral ventricle. One can describe it more holistically as a curved and recurved sheet of the cortex that folds into the temporal lobe’s medial surface.
2. Anatomical enumeration of hippocampus
2.1 Embryology of hippocampus
In the human embryo, the hippocampal formation develops in relation to the medial surface of each cerebral hemisphere close to the choroid fissure of the lateral ventricle [3]. It is at first approximately, C-shaped in accordance with the outline of the body and inferior horn of the ventricle. The upper part of the formation is, however, separated from the ventricle because of the development of the corpus callosum between the two [4]. For the same reason, this part of the formation remains underdeveloped and is represented by a thin layer of gray matter, lining the upper surface of the corpus callosum. This layer is the indusium griseum. Within the indusium griseum are embedded two bundles of longitudinally running fibers called the medial and lateral longitudinal striae (on each side of the midline). Posteriorly, the indusium griseum is continuous with a thin layer of gray matter related to the inferior aspect of the splenium of the corpus callosum [3].
This gray matter is the splenial gyrus or gyrus fasciolaris. The splenial gyrus runs forward to become continuous with the dentate gyrus, present in relation to the inferior horn of the lateral ventricle. In the region of the inferior horn of the lateral ventricle, the developing hippocampus is pushed into the cavity of the ventricle because of the great development of the neighboring neocortex. The hippocampal formation is best developed in this region and forms the hippocampus. This term includes the dentate gyrus [4].
2.2 Gross anatomy of hippocampus
The hippocampus has three distinct zones: the dentate gyrus, the hippocampus proper, and the subiculum. The dentate gyrus and hippocampus proper form two C-shaped rings that interlock. The subiculum is thus a transition zone, linking the hippocampus proper with the dentate gyrus [5].
The parahippocampal gyrus and cingulate sulci are located on the medial surface of the hemisphere, forming a C-shaped ring. The medial temporal lobe cortex includes major subdivisions such as the hippocampus and the entorhinal cortex. This five centimeter-long hippocampus (from the anterior end at amygdala to posterior end near the splenium of the corpus callosum) divides into a head, body, and tail [5]. The head is expanded and bears two or three shallow grooves called pes hippocampi. The head of the hippocampus is part of the posterior half of the triangular uncus and is separated inferiorly from the parahippocampal gyrus by the uncal sulcus. The alveus, which is the surface of the hippocampus, is covered by the ependymal tissue inside the ventricular cavity [5].
The fornix, which is the main outflow bundle out of the hippocampus, wraps around the thalamus, where it then becomes separated by the choroidal fissure and the choroid plexus. The hippocampus contains parts like the fimbria, crus, body, and column. The fimbria forms where alveus fibers converge along the medial portion of the lateral ventricle’s inferior horn. The white matter of the fimbria separates to form a crux of the ipsilateral fornix at a point beyond the splenium of the corpus callosum.
The anterior choroidal artery runs medially and superiorly to the uncus, between the ambient and semilunar gyrus [5]. It then sends perforating arteries to reach deeper structures. The uncus is closely related to the middle cerebral arteries and its lenticulostriate arteries. The posterior cerebral artery and the basal vein supplies and drains the caudal part of the head of the hippocampus that faces the crus cerebri and crural cistern [6]. Internal cerebral veins drain into thalamostriatal basal ganglia, thalamus, internal capsule, tela choroidea of three ventricles, and hippocampus. The veins on each side unite to form the internal cerebral vein.
2.3 Histology of hippocampus
Stratum Oriens: It is the next layer superficial to the alveus. The cell bodies of inhibitory basket cells and horizontal trilaminar cells, named for their axons innervating three layers, the oriens, Pyramidal, and radiatum, are located in this stratum. The basal dendrites of Pyramidal neurons are also found here, where they receive input from other Pyramidal cells, septal fibers, and commissural fibers from the contralateral hippocampus (usually recurrent connections, especially in CA3 and CA2.) In rodents the two hippocampi are highly connected, but in primates this commissural connection is much sparser [3].
Stratum pyramidale: It contains the cell bodies of the Pyramidal neurons, which are the principal excitatory neurons of the hippocampus (Figure 2). This stratum tends to be one of the more visible strata to the naked eye. In region CA3, this stratum contains synapses from the mossy fibers that course through stratum lucidum. This stratum also contains the cell bodies of many interneurons, including axo-axonic cells, bistratified cells, and radial trilaminar cells [3].
Figure 2.
Layers of the hippocampus.
Stratum Luciderm: It is one of the thinnest strata in the hippocampus and only found in the CA3 region. Mossy fibers from the dentate gyrus granule cells course through this stratum in CA3, though synapses from these fibers can be found in statim luciderm [3].
Stratum Radiatum: Like stratum oriens, it contains septal and commissural fibers. It also contains Schaffer collateral fibers, which are the projection forward from CA3 to CA1. Some interneurons that can be found in more superficial layers can also be found here, including basket cells, bistratified cells, and radial trilaminar cells [3].
Stratum Lacunosum: It is a thin stratum that too contains Schaffer collateral fibers, but it also contains perforant path fibers from the superficial layers of entorhinal cortex. Due to its small size, it is often grouped together with stratum moleculare into a single stratum called stratum lacunosum-moleculare [3].
Stratum Moleculare: It is the most superficial stratum in the hippocampus. Here, the perforant path fibers form synapses onto the distal, apical dendrites of Pyramidal cells [3].
Hippocampal Sulcus: Hippocampal Sulcus or fissure is a cell-free region that separates the CA1 field from the dentate gyrus. Because the phase of recorded theta rhythm varies systematically through the strata, the sulcus is often used as a fixed reference point for recording Electroencephalogram (EEG) as it is easily identifiable [3].
Dentate Gyrus: The dentate gyrus is composed of a similar series of strata.
The Polymorphic Layer: It is the most superficial layer of the dentate gyrus and is often considered a separate subfield (as the hilus). This layer contains many interneurons, and the axons of the dentate granule cells pass through this stratum on the way to CA3 [4].
Stratum Granulosum: It contains the cell bodies of the dentate granule cells.
Stratum Moleculare, Inner Third: It is where both commissural fibers from the contralateral dentate gyrus run and form synapse as well as where inputs from the medial septum terminate, both on the proximal dendrites of the granule cells [4].
Stratum Moleculare: External two-thirds is the deepest of the strata, sitting just superficial to the hippocampal sulcus across from stratum moleculare in the CA fields. The perforant path fibers run through this strata and making excitatory synapses onto the distal apical dendrites of granule cells [4].
3. The hippocampal system
The role of the hippocampus in relational memory is in binding together multiple inputs to create and allow for the storage of representations of the associations among the constituent elements of scenes and events [7]. This function ultimately results in the storage of long-term memory in widespread cortical regions. The hippocampus communicates with widespread regions of cortex through a group of highly interconnected brain regions in the medial temporal lobe. Therefore, aberrant activation of the hippocampus would affect perceptual cortical regions, especially those showing high functional connectivity with the hippocampal system.
The hippocampal system consists of the dentate gyrus, cornu ammonis (CA) fields, and the subiculum. The dentate gyrus is an input region, which receives input from the entorhinal cortex. The cornu ammonis (CA) fields of the hippocampus consist of pyramidal cells and are usually subdivided into four regions (CA1–CA4). The area that is often referred to as the parahippocampal gyrus in humans actually consists of several subregions.
The dorsal part of the parahippocampal gyrus (inferior to the hippocampal fissure), throughout its extent, is called the subiculum [8]. The entorhinal cortex provides the major input to the hippocampus and also receives output from the CA1 layer via the subiculum [9]. The entorhinal cortex provides input to the hippocampus through two pathways, one projecting to the dentate gyrus and CA3 fields and the other to CA1 and the subiculum. The subiculum then sends a major input back to the entorhinal cortex.
The entorhinal cortex has its main reciprocal connections with the perirhinal and parahippocampal cortices. Hence, the hippocampus communicates with widespread cortical areas through the entorhinal, perirhinal, and parahippocampal cortices [10]. The hippocampus also contains fiber pathways that run longitudinally throughout its extent [11]. This would allow for the excitation between disparate portions of the hippocampal formation. The entorhinal cortex extends from the amygdala (anteriorly) to approximately 10 mm posterior to the most anterior aspect of the hippocampal fissure.
It had been reported that the hippocampus allows for the consolidation of memory in other cortical regions and that this process proceeds over a number of years. Hence, long-term memory is not actually stored in the hippocampus or, if it is, the hippocampal representation is not necessary for the retrieval of long-term memories after a period of several years. The conceptualization of memory and perception as separate is at odds with this formulation of hippocampal function. Information flows from the cortex to the hippocampus and back out to cortex; this is how memories are formed. In other words, memories are formed via the interplay over time between perceptual regions, including higher-order association cortex and the hippocampus [12, 13].
The physiology of the hippocampus is unique and endows the region with a high level of plasticity that is important for learning and memory; this property also has important implications for neurodegenerative disorders. Neurogenesis also occurs in the hippocampus; hence, it undergoes changes throughout the lifespan. The hippocampus, particularly, the CA1 layer (output layer), one subfield, has the highest concentration of N-methyl-D-aspartate (NMDA) receptors in the brain [14]. NMDA receptors are a type of glutamate receptor whose activity underlies long-term potentiation (LTP), a process that may underlie learning and memory [15].
Neuronal activity reflects the fact that higher-order representational regions from widespread brain regions converge within the hippocampal system. Single unit (neuronal) activity has been shown to be related to a wide variety of stimuli within various tasks or contexts in humans and other animals, including words, pictures locations, odors, and sounds [16]. Unit recording studies also show that although hippocampal system function may not be necessary for the maintenance of short-term memory or working memory, it is active during these types of memory tasks. In fact, if the contents of working memory cannot be actively rehearsed or if this process is interrupted, then the hippocampus is needed to hold the memory, even at short time periods [17]. Hence, trace conditioning is often affected by hippocampal lesions (where there is a temporal gap between the stimuli used), whereas other types of conditioning are intact [18].
An examination of the connectivity of the hippocampal system along with data from single unit recording in the hippocampus necessitates the view that hippocampus is active during much of daily life. For example, the place cells that are recorded in the hippocampus are active regardless of whether or not the memory of spatial location is required at the moment of recording a result also seen for nonspatial stimuli [19]. The online or continuously active role of the hippocampus has recently been formally investigated in recent human neuroimaging studies [20].
The hippocampus may create memory using automatic, obligatory, and ongoing binding operations. Relational memory theory posits that hippocampal-dependent relational processing permits the integration and comparison of discrete experiences and items. In this manner, the hippocampus facilitates the maintenance and integration of the contents of consciousness (consciously perceived stimuli) with representations that are just outside the current contents of consciousness [21].
In this way, the hippocampus could allow for the near-simultaneous activation of representations in cortex that were originally processed with a longer time gap between them. This type of simple mechanism could allow for the association of perceptual stimuli with internally activated memories or representations, resulting in the integration of incoming stimuli with existing cortical associative networks.
The unique physiology of the hippocampus and high concentrations of NMDA receptors allows for relatively high levels of plasticity that are needed for declarative learning and memory. However, this property also confers a unique vulnerability; NMDA receptor abnormalities have also been proposed to play a major role in neurodegenerative disorders [22].
In addition to being the most frequent cite of damage after anoxia or ischemia, the hippocampal system (along with the adjacent amygdala) is the most frequent cite of epileptic foci [23]. The sensitivity of the hippocampus to insult may play a role in the development of epilepsy following traumatic brain injury [24]. It has been reported that hippocampus contains the highest concentration of glucocorticoid (stress hormone) receptors in the brain. These stress hormones can regulate LTP and may increase the likelihood of excitotoxic cell death with prolonged exposure (Figure 3) [25].
Figure 3.
Representation of connection within the hippocampus. Source: (rolls, 2017).
3.1 The involvement of hippocampus in memory
The hippocampus, for example, is essential for memory function, particularly the transference from short- to long-term memory, control of spatial memory and behavior. The hippocampus is one of the few areas of the brain capable actually growing new neurons, although this ability is impaired by stress-related glucocorticoids. The amygdala also performs a primary role in the processing and memory of emotional reactions and social and sexual behavior, as well as regulating the sense of smell [26].
Another subcortical system (inside the cerebral cortex) which is essential to memory function is the basal ganglia system, particularly the striatum (or neostriatum) which is important in the formation and retrieval of procedural memory. The hippocampal region has been linked to memory function since patient H.M. was first described [27], the hippocampus itself has only recently been identified as a critical structure. Neuropathological findings from a patient with permanent circumscribed memory impairment following global ischemia revealed bilateral lesion involving the entire CA1 field of the hippocampus [28]. As a result of this, damage to the hippocampus itself is sufficient to produce clinically significant and long-lasting memory impairment. Furthermore, it has been reported that high-resolution Magnetic Resonance Imaging (MRI) studies of patients with circumscribed memory impairment revealed that the hippocampal formation was reduced in size [29, 30]. The largest area of activation in the memory recall task was in the posterior medial temporal lobe (PMTL) in the region of the hippocampus and the parahippocampal gyrus. There is no activation at the amygdala. Indeed, even incomplete damage to the hippocampus is sufficient to impair memory. The two structures most frequently implicated have been the mammillary nuclei (MN) and the mediodorsal thalamic nucleus (MD) [31, 32]. Idea that damage to the MN impairs memory originated in the finding that the MN are consistently damaged in alcoholic Korsakoff’s syndrome.
3.2 Functions of hippocampus
Three phases of memory include (1) registration, (2) storage, and (3) retrieval of information. The hippocampus, parahippocampal region of the medial temporal lobe, and the neocortical association area have been shown through autopsy and imaging studies to be essential for memory processing. Impairment of short-term memory leading up to an inability to form new memories occurs when there is bilateral damage to the above-mentioned regions [33]. The hippocampus is closely associated with the amygdala, hypothalamus, and mammillary bodies such that any stimulation of the nearby parts also marginally stimulates the hippocampus. There are also high outgoing signals from the hippocampus, especially through the fornix into the anterior thalamus, hypothalamus, and greater limbic system. The hippocampus is also very hyperexcitable, meaning it can sustain weak electrical stimulus into a long, sustained stimulation that helps in encoding memory from olfaction, visual, auditory, and tactile senses.
In lower animals, the hippocampus helps them determine if they will eat certain foods, based on olfactory discernment, avoid danger, respond to sexual signals through pheromones, or react to life and death decisions. The hippocampus is a site for decision-making and committing information to memory for future safety uses. Thus, it has a mechanism to convert short-term memory into long-term memory, consolidating the verbal and symbolic thinking into information that can be accessed when needed for decision-making [33].
3.3 Acetylcholine in the hippocampus
It has been shown that cholinergic neurons in the medial septum regulate hippocampal circuits. Optogenetic stimulation of cholinergic neurons in the medial septum area not only causes changes in the firing activity of hippocampal neurons but also modulates theta-band oscillations in the hippocampus in vivo [34]. Experimental and computer modeling studies have shown that Ach specifically inhibits intrinsic pathways, which are part of the memory consolidation circuits, while facilitating afferent projections, which are part of the encoding pathway [35]. Acetylcholine inhibits the recurrent pathway in the CA3 region via the activation of muscarinic ACh receptors in interneurons [36]. This ensures that the circuits that carry extrinsic information are preferentially activated, while the intrinsic projections are toned down [37]. In the hippocampal CA1 region, ACh is known to potentiate the Schaffer collateral pathway, via the activation of α7 or non-α7 nicotinic ACh receptors located in pyramidal neurons and GABAergic interneurons [38]. However, these results are controversial. For example, other studies have shown that the Schaffer collateral pathway is instead inhibited by ACh [39]. One explanation for this discrepancy is that the effect of ACh on synaptic plasticity is timing-dependent. It has been reported that cholinergic input can cause either long-term potentiation or short-term depression, depending on the timing of cholinergic input relative to glutamatergic input to the CA1 [40, 41]. In addition, the effect of ACh may vary depending on which cholinergic receptor subtype is activated in different conditions. In the dentate gyrus, ACh has been shown to increase long-term potentiation via activation of nicotinic and muscarinic receptors [42, 43]. In addition, septal cholinergic projections have been shown to activate astrocytes to modulate dentate granule cells [44].
3.4 Complexity of acetylcholine (ach) modulation on cognitive function
ACh’s modulation of cognitive function is selective to hippocampus-dependent memory, specifically affecting spatial but not procedural memory.
The method of cholinergic modulation can result in different outcomes. For example, optogenetic manipulation of cholinergic neurons is more physiological but is not as selective as antagonism of ACh receptors (AChRs).
ACh has differential effects on memory encoding and consolidation, favoring the pathways involved in encoding.
ACh can exert different responses depending on which receptor subtypes ACh activates, each of which has distinct desensitization characteristics.
3.5 Diseases of the hippocampus
An understanding of the location and functions of the hippocampus will give us a better idea about the associated diseases. The hippocampus is the part of the brain located in the inner fold of the bottom middle section of the brain. It is a part of the limbic system responsible for the management of feeling and reacting. The main function is for human learning and memory. It is responsible for the retrieval of the main types of memories namely declarative and spatial memory, and there are also short and long term memories.
Hippocampus though known to be important in learning and memory but also important in:
Spatial navigation: the process by which organisms use multiple cue sources such as path integration, magnetic cues, landmarks, and beacons to determine the route to a goal and then travel that route. The hippocampus do this by functioning like an internal GPS helping to figure out where we are, have we been here before, and where we can go next [45].
Emotional behavior: though emotional behavior is mainly regulated by the amygdala, the hippocampus and amygdala both have reciprocal connections, which can hereby influence each other (latter affects emotions more than former) [46].
Regulation of hypothalamic functions: due to the fact that the hippocampus has projections to hypothalamus, hereby affecting the release of adrenocorticotropic hormones. The more reason why patients with atrophied hippocampus have increasing levels of cortisol [47].
Declarative memories are related to facts and events, while spatial memories involve pathways or routes which are stored in the right hippocampus, and short-term memories are converted into long-term memories in the hippocampus and stored in other parts of the brain. Since the hippocampus is a plastic and vulnerable structure that gets damaged by a variety of stimuli resulting in a variety of neurological and psychiatric disorders which produce changes ranging from molecules to morphology. The following are some of the common conditions in which atrophy of human hippocampus has been reported including long-term exposure to high levels of stress [48].
4. Alzheimer’s disease
Atrophy of hippocampal region in brains is one of the most consistent characteristics of Alzheimer’s disease (AD). It is regarded as the earliest brain region and the most severely affected. A popular hypothesis called “hippocampo-cortical-dissociation” has proposed that early damage to hippocampus causes “dissociation” between hippocampus and cerebral cortex, leading to failure of registration of information emanating from hippocampus. Some amount of hippocampal atrophy is seen in all patients with AD [48]. A number of neurotransmitter alterations can also occur in brains of AD such as noradrenergic, serotonergic, and glutaminergic regions and corresponding loss of neuron in the hippocampal region.
4.1 Depression and stress
Ever since the biological basis of depression is getting revealed, there have been accumulating evidence that prolonged depression can lead to volume loss of hippocampus. With the duration of depression has been correlated with severity of hippocampal atrophy. Evidence suggests that atrophy produced may be permanent and persist long even though depression has undergone remission. It has been hypothesized that it could result to affective disturbance seen in depression. It is believed that this could be as a result of prolonged stress generated as a result of depression. Retraction of cell volume and/or suppression of hippocampal neurogenesis could be responsible in this case [49].
4.2 Schizophrenia
There is a reason to believe that disturbance in hippocampus is responsible for the production of psychotic symptoms in schizophrenia. Hippocampal volume reduction is one of the most consistent findings found in MRI of schizophrenic patients. Though functional and biochemical abnormalities have also been identified initially the pathophysiology of schizophrenia mainly focusing on prefrontal cortex, now hippocampus is being considered for last 20 years or so. There is now a compelling data to suggest that there are anatomical and functional aberrations as a result of neuronal disturbances in hippocampus of schizophrenic patients. Evidence gathered from MRI, Positron Emission Tomography (PET), and Magnetic Resonance Spectroscopy (MRS) studies of disturbances within hippocampus of schizophrenia. Volume reduction in hippocampus of schizophrenia is modest and not as marked as that seen in AD. Still, biochemical and functional disturbances provide a reliable evidence of involvement of hippocampus in pathophysiology of schizophrenia [49].
4.3 Epilepsy
Up to 50–75% of patients with epilepsy may have hippocampal sclerosis upon postmortem analysis, in case they died and had medically refractory temporal lobe epilepsy. It is, however, not clearly known if epilepsy is generated as a result of hippocampal sclerosis or repeated seizures damage hippocampus. Therefore, there is not much clarity whether hippocampal atrophy is a cause or consequence of recurrent seizures [50, 51] Mechanism of hippocampal sclerosis in epilepsy that has been reported might be related to the development of uncontrolled local hippocampal inflammation and blood–brain barrier damage [51] Recurrent seizures leading to cytoskeletal abnormalities, neurotransmitter alterations, and hypoxia may be additional associated factors. Developing hippocampus may be more susceptible to damage compared to mature one [50]. Recent evidence also suggests that hippocampal sclerosis in epilepsy may be an acquired process with accompanying re-organizational dysplasia and an extension of mesial temporal sclerosis rather than a separate pathological entity [52]. Indicating significant progress is being made in understanding relationship between hippocampal sclerosis and epilepsy. It is believed that hippocampus has an inhibitory effect on seizure threshold (i.e. it keeps it elevated). Once it gets damaged, then seizures become more intractable. Surgical resections of the hippocampus have been suggested as the most successful treatment for medication-refractory medial temporal lobe epilepsy due to hippocampal sclerosis [53]. It was also discovered that patients with AD with seizures had hippocampal atrophy, and cause of hippocampal atrophy in epilepsies is not known, but autoimmunity has been proposed as one of the mechanisms [54, 55].
4.4 Food that enhances the hippocampus
Brain foods as well as hippocampus are those that are rich in antioxidants, healthy fats, vitamins, and minerals. They provide your brain with energy and aid in protecting brain cells, which helps ward off development of brain diseases such as dementia. There is no single brain food can ensure a sharp brain as age declines. Nutritionists emphasize that the most important strategy is to follow a healthy dietary pattern that includes a lot of fruits, vegetables, legumes, and whole grains. Diet that is rich in omega-3 fatty acids is garnering appreciation for supporting cognitive processes in humans [56] and upregulating genes that are important for maintaining synaptic function and plasticity in rodents [57].
Fish (salmon), flax seeds, krill, chia, kiwi fruit, butternuts, and walnuts are sources of omega-3 fatty acids (e.g. docosahexaenoic acid). They have ameliorating effect of cognitive decline in the elderly [58], basis for treatment in patients with mood disorders [59], improvement of cognition in traumatic brain injury in rodents [60], and amelioration of cognitive decay in mouse model of Alzheimer’s disease [61]. Butter, ghee, suet, lard, coconut oil, cottonseed oil, palm kernel oil, dairy products (cream and cheese), and meat which are sources of saturated fat promote cognitive decline in adult rodents [62], aggravation of cognitive impairment after brain trauma in rodents [60], and exacerbation of cognitive decline in aging humans.
5. Conclusions
Hippocampus is an extension of cerebral cortex situated deep into temporal lobe. It is a vulnerable and plastic structure. It gets damaged by a variety of stimuli and hence is important clinically both diagnostically and therapeutically. Currently, it is one of the markers of cognitive decline and diagnosis of AD. It is also a prognostic marker in research setting. Drugs that are able to cause slow-down of atrophy or reversal are actively being sought. These could then potentially have disease-modifying effects.
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