Hippocampus

If ancient Greek mythology called the Hippocampus the lord of fish, representing him in the form of a sea monster - a horse with a fish tail, then the hippocampus of the brain, which is its important structure, received this name due to the similarity of its shape in the axial plane with an unusual needle-shaped fish of the genus Hippocampus - the sea skate.

By the way, the second name of the curved internal structure of the temporal lobe of the brain, given to it by anatomists in the middle of the 18th century - Ammon's horn (Cornu Ammonis), is associated with the Egyptian god Amun (in the Greek form - Ammon), who was depicted with ram's horns.

The structure of the hippocampus and its structure

The hippocampus is a complex structure deep in the  temporal lobe of the brain : between its medial side and the lower horn of the  lateral ventricle , forming one of its walls.

Elongated interconnected structures of the hippocampus (folds of the gray matter of the archicortex folded into each other) are located along the longitudinal axis of the brain, one in each of the temporal lobes: the right hippocampus and the left hippocampus contralateral to it. [1]

In adults, the size of the hippocampus - length from front to back - ranges from 40-52 mm.

The main structures are the hippocampus proper (Cornu Ammonis) and the dentate gyrus (Gyrus dentatus); they also highlight the subicular cortex, which is the area of the gray matter of the cerebral cortex surrounding the hippocampus.[2]

The Ammon's horn forms an arc, the rostral (front) part of which is enlarged and is defined as the head of the hippocampus, which bends back and downward, forming on the medial side of the temporal lobe a hippocampal hook or uncus (from Latin uncus - hook) - (Uncus hippocampi). Anatomically, it is the anterior end of the parahippocampal gyrus (Gyrus parahippocampi), which is curved around the hippocampus itself and protrudes into the bottom of the temporal (lower) horn of the lateral ventricle.

Also in the rostral part there are thickenings in the form of three to four separate protrusions of the cortical gyri, which are called the fingers of the hippocampus (Digitationes hippocampi).

The middle part of the structure is defined as the body, and the part of it, called the alveus, is the bottom of the lateral ventricle (temporal horn) of the brain and is almost completely covered by the choroid plexus, which is a combination of the pia mater and ependyma (the tissue lining the ventricular cavity). The fibers of the white matter of the alveus are collected in thickened bundles in the form of a fringe or fimbria (Fimbria hippocampi), then these fibers pass into the fornix of the brain.

Below the hippocampus is its main outlet - the upper flat part of the parahippocampal gyrus, called the Subiculum. This structure is separated by a shallow rudimentary cleft or sulcus of the hippocampus (Sulcus hippocampalis), which is a continuation of the sulcus of the corpus callosum (Sulcus corporis callosi) and runs between the parahippocampal and dentate gyri. [3]

And the dentate gyrus of the hippocampus, also called the parahippocampus, is a three-layered concave groove separated from the fibria and subiculum by other grooves.

It should also be borne in mind that the hippocampus and adjacent dentate and parahippocampal gyrus, subiculum and entorhinal cortex (part of the temporal lobe cortex) form the hippocampus formation - in the form of a bulge at the bottom of the temporal horn of the lateral ventricle.

In this zone - in the medial surfaces of both hemispheres of the brain (Hemispherium cerebralis) - a set of brain structures included in the limbic system of the brain is localized  . The limbic system and the hippocampus, as one of its structures (along with the amygdala, hypothalamus, basal ganglia, cingulate gyrus, etc.), are connected not only anatomically, but also functionally. [4]

The blood supply to the hippocampus is carried out by the vessels that supply blood to the temporal lobes of the brain, that is, the branches of the middle cerebral artery. In addition, blood enters the hippocampus through the branches of the posterior cerebral artery and the anterior choroidal artery. And the outflow of blood goes through the temporal veins - anterior and posterior.

Hippocampal neurons and neurotransmitters

The heterogeneous hippocampal cortex - allocortex - is thinner than the cerebral cortex and consists of the superficial molecular layer (Stratum molecular), the middle layer of the Stratum pyralidae (consisting of pyramidal cells) and a deep layer of polymorphic cells.

Depending on the characteristics of the cellular structure of the Ammon, the horn is divided into four different areas or fields (the so-called Sommer sectors): CA1, CA2, CA3 (the area of the hippocampus itself, covered with the dentate gyrus) and CA4 (in the dentate gyrus itself).

Together, they form a neural trisynaptic circuit (or circuit), in which the functions of transmitting nerve impulses are performed by hippocampal neurons, in particular: excitatory pyramidal neurons of CA1, CA3 and subiculum fields characteristic of the structures of the anterior regions of the brain. Glutamatergic pyramidal neurons with dendrites (afferent processes) and axons (efferent processes) are the main type of cells in the  nervous tissue of the  hippocampus.

In addition, there are stellate neurons and granular cells, concentrated in the layer of granular cells of the dentate gyrus; GABAergic interneurons - multipolar insertion (associative) neurons of the CA2 field and parahippocampus; basket (inhibitory) neurons of the CA3 field, as well as the intermediate OLM interneurons recently identified in the CA1 region. [5]

Chemical messengers that are released from the secretory vesicles of the main cells of the hippocampus into the synaptic cleft to transmit nerve impulses to target cells - neurotransmitters or neurotransmitters of the hippocampus (and the entire limbic system) - are divided into excitatory and inhibitory (inhibitory). The former include glutamate (glutamic acid), norepinephrine (norepinephrine), acetylcholine, and dopamine, while the latter include GABA (gamma-aminobutyric acid) and serotonin. Depending on which neurotransmitters act on the transmembrane nicotinic (ionotropic) and muscarinic (metabotropic) receptors of the hippocampal neuronal circuits, excitation or suppression of the activity of its neurons occurs. [6]

Functions

What is the brain hippocampus responsible for, what functions does it perform in the central nervous system? This structure is connected with the entire cerebral cortex by indirect afferent pathways passing through the entorhinal cortex and subiculum and is involved in the processing of cognitive and emotional information. By far, the link between the hippocampus and memory is best known, and researchers are also exploring how the hippocampus and emotion are linked.

Neuroscientists studying the function of the hippocampus have topographically divided it into the posterior part or dorsal and the anterior or ventral part. The posterior part of the hippocampus is responsible for memory and cognitive functions, and the anterior part is responsible for the expression of emotions. [7]

It is believed that from a variety of sources along the adherent nerve fibers (commissures) of the temporal lobe cortex, information comes to the hippocampus, which it encodes and combines. From short-term memory,  [8]it forms a long-term declarative memory (about events and facts) due to long-term potentiation, that is, a special form of neural plasticity - an increase in the activity of neurons and synaptic strength. Retrieval of information about the past (memories) is also regulated by the hippocampus. [9]

In addition, the structures of the hippocampus are involved in the consolidation of spatial memory and mediate orientation in space. This process consists in cognitive mapping of spatial information, and as a result of its integration in the hippocampus, mental representations of the location of objects are formed. And for this there is even a special type of pyramidal neurons - place cells. Presumably, they also play an important role in episodic memory - fixing information about the environment in which certain events took place. [10]

As for emotions, the most important of the cerebral structures that are directly related to them is the limbic system and its integral part - the hippocampus. [11]

And in this regard, it should be clarified what the hippocampus circle is. It is not the anatomical structure of the brain, but the so-called medial limbic chain or Papesian emotional circle. Considering the hypothalamus as the source of human emotional expression, the American neuroanatomist James Wenceslas Papez put forward his concept of the formation and cortical control of emotions and memory in the 1930s. In addition to the hippocampus, this circle included the mastoid bodies of the base of the hypothalamus, the anterior nucleus of the thalamus, the cingulate gyrus, the temporal lobe cortex surrounding the hippocampus, and some other structures. [12]

Further studies clarified the functional connections of the hippocampus. In particular, the amygdala (Corpus amygdaloideum), which is located in the temporal lobe (in front of the hippocampus), was recognized as the emotional center of the brain responsible for the emotional assessment of events, the formation of emotions and the adoption of emotional decisions. As part of the limbic system, the hippocampus and amygdala / amygdala / amygdala work together in stressful situations and when feelings of fear arise. The parahippocampal gyrus is also involved in the negative emotional reaction, and the consolidation of emotionally expressed (terrible) memories occurs in the lateral nuclei of the amygdala. [13]

Numerous synaptic connections are located in the midbrain of the  hypothalamus  and hippocampus, which determines their participation in  the stress response . Thus, the anterior part of the hippocampus, providing negative feedback, controls the stress responses of the functional neuroendocrine axis of the hypothalamus-pituitary-adrenal cortex. [14]

In search of an answer to the question of how the hippocampus and vision are related, neuropsychological studies have established participation in the visual recognition of complex objects and the memorization of objects of the parahippocampal gyrus and the peririnal cortex (part of the cortex of the medial temporal lobe).

And what connections the hippocampus and the olfactory brain (Rhinencephalon) have is known for sure. First, the hippocampus receives information from the olfactory bulb (Bulbus olfactorius) through the amygdala. Second, the hippocampal hook (uncus) is the olfactory center of the cerebral cortex and can be attributed to the rhinencephalon. Thirdly, the parahippocampal gyrus, which stores information about odors, is also included in the cortical region, which is responsible for smell. [15]Read more -  Smell

Diseases of the hippocampus and their symptoms

Experts attribute the hippocampus to a rather vulnerable structure of the brain, its damage (including traumatic brain injury) and related diseases can cause various symptoms - neurological and mental.

Modern neuroimaging methods help to identify morphometric changes in the hippocampus (its volume), which are present in hypoxic damage and certain diseases of the brain, as well as in its reduction deformities.

Asymmetry of the hippocampus is considered an important clinical sign, since, presumably, the left and right hippocampus are affected differently during aging. According to some studies, the left hippocampus plays the main role in episodic verbal memory (verbal recollection of memories), and the right hippocampus plays a major role in the consolidation of spatial memory. According to the measurement, in people over 60 years of age, the difference in their volumes is 16-18%; it increases with age, and in comparison with women, men have more asymmetry. [16]

A slight decrease in the hippocampus, which occurs with age, is considered normal: atrophic processes in the medial temporal lobe and entorhinal cortex begin to occur closer to the seventh decade. But dramatically shrinking the brain's seahorse increases the risk of dementia, the early symptoms of which are brief episodes of memory loss and disorientation. Read more in the article -  Symptoms of dementia

The reduction of the hippocampus is much more pronounced in  Alzheimer's disease . However, it is not yet clear whether this is the result of this neurodegenerative disease or is a prerequisite for its development. [17]

According to studies, in patients with generalized  depressive disorder  and stress disorders of post-traumatic etiology, there is a bilateral and unilateral decrease in the volume of the hippocampus - by 10-20%. Long-term depression is also accompanied by a decrease or impairment of neurogenesis in the hippocampus. [18]According to neurophysiologists, this is due to increased levels of cortisol. This hormone is produced and released by the adrenal cortex in response to physical or emotional stress, and its excess negatively affects the pyramidal neurons of the hippocampus, impairing long-term memory. It is because of the high level of cortisol that the hippocampus shrinks in patients with  Itsenko-Cushing's disease . [19], [20]

• Read also -  Symptoms of stress

A decrease in the number or alteration of nerve cells in the hippocampus can also be associated with inflammatory processes (neuroinflammation) in the temporal lobe of the brain (for example, with bacterial meningitis, with herpes simplex virus type I or II encephalitis) and prolonged activation of microglia, whose immune cells (macrophages ) release pro-inflammatory cytokines, proteinases and other potentially cytotoxic molecules.

The volume of this cerebral structure can be reduced in patients with   brain gliomas , since tumor cells produce the neurotransmitter glutamate into the extracellular space, the excess of which leads to the death of hippocampal neurons.

In addition, a number of studies with MRI volumetric analysis of the hippocampus have recorded its decrease in traumatic brain injury, epilepsy, moderate cognitive impairment, Parkinson's and Huntington's diseases,  schizophrenia , Down and Turner syndromes. [21]

Malnutrition of the nervous tissue - hypotrophy of the hippocampus - may have an ischemic etiology after suffering strokes; in drug addiction, in particular, opioid, hypotrophy is observed, due to disorders of dopamine metabolism by psychoactive substances.

Disorders caused by the lack of certain elements affect the trophism of the nervous tissue of the entire hippocampus, negatively affecting the functioning of the central nervous system. So, vitamin B1 or thiamine and the hippocampus are connected by the fact that in cases of chronic deficiency of this vitamin, the processes of formation of short-term memory are disrupted. It turned out that with a lack of thiamine (the risk of which is increased in alcoholics) in the dentate gyrus and hippocampal fields CA1 and CA3, the number of pyramidal neurons and the density of their afferent processes can decrease, which is why there are disruptions in the transmission of nerve impulses. [22],  [23]Long tiaminovaya failure can cause  Korsakoff syndrome .

A progressive decrease in the volume of nervous tissue with the loss of neurons - atrophy of the hippocampus - occurs in almost the same diseases, including Alzheimer's and Itsenko-Cushing's diseases. Risk factors for its development are considered cardiovascular diseases, depression and stress conditions, status epilepticus, diabetes mellitus, arterial hypertension,  [24]obesity. Symptoms include memory loss (in Alzheimer's, prior to anterograde  amnesia )  [25],  [26]difficulty with familiar processes, spatial definition, and verbal expression. [27]

If the structural organization of the cells of the fields of the Ammon's horn and the subiculum region is disturbed and a part of the pyramidal neurons (atrophy) is lost - with the expansion of the interstitium and the proliferation of glial cells (gliosis) - the sclerosis of the hippocampus is determined - mesial sclerosis of the hippocampus, mesial temporal or mesial temporal lobe sclerosis. Sclerosis occurs in patients with dementia (causing loss of episodic and long-term memory) and also leads to  temporal lobe epilepsy . [28]Sometimes it is defined as limbic temporal or hippocampal, that is, hippocampal epilepsy. Its development is associated with the loss of inhibitory (GABAergic) interneurons (which reduces the ability to filter afferent signals of the entorhinal cortex and leads to hyperexcitability), impaired neurogenesis and proliferation of axons of granular cells of the dentate zilin. More information in the article -  Epilepsy and epileptic seizures - Symptoms

As evidenced by clinical practice, hippocampal tumors are rarely found in this cerebral structure, and in most cases it is a ganglioglioma or dysembryoplastic neuroepithelial tumor - a slowly growing benign glioneuronal neoplasm, consisting mainly of glial cells. Most often occurs in childhood and young age; the main symptoms are headache and intractable chronic convulsions.

Congenital anomalies of the hippocampus

With such malformations of the cerebral cortex, such as focal cortical dysplasia, hemimegalencephaly (unilateral enlargement of the cerebral cortex), schizencephaly (the presence of abnormal cortical clefts), polymicrogyria (decrease in convolutions), as well as accompanied by convulsions and visual-spatial disturbances of the periventricular nodule hippocampus.

Abnormal enlargement of the amygdala and hippocampus was identified by researchers in the presence  of early childhood autism syndrome . Bilateral enlargement of the hippocampus is observed in children with  lissencephaly of the brain , abnormal thickening of the gyrus (pachygiria), or with subcortical laminar heterotopy - a doubling of the cerebral cortex, a manifestation of which is epileptic seizures. More information in the materials:

• Brain malformations
• Dysgenesis of the brain

The hypoplasia of the hippocampus, and often of the corpus callosum, associated with underdevelopment of the brain, is detected in newborns with severe encephalopathy with a mutation of the WWOX gene encoding the oxidoreductase enzyme. This congenital anomaly, leading to early death, is manifested by the infant's lack of spontaneous movement and response to visual stimuli, as well as seizures (which appear several weeks after birth).

Inversion of the hippocampus - a change in its anatomical position and shape - also represents an intrauterine malformation of the hippocampus itself (Cornu Ammonis), the formation of which from the folds of the gray matter of the archicortex is completed by the 25th week of pregnancy.

Incomplete inversion of the hippocampus, as well as malrotation of the hippocampus or inversion of the hippocampus with malrotation, is the formation of a spherical or pyramidal hippocampus, which is more often observed in the left temporal lobe - with a decrease in size. Morphological changes in nearby furrows may be observed. The anomaly is detected in patients with and without seizures, in the presence of other intracranial defects and in cases of their absence.

A congenital anomaly is also a hippocampal cyst - a small cavity filled with cerebrospinal fluid (an expanded perivascular space bounded by a thin wall) of a rounded shape. Residual cysts of the hippocampus, synonymous with remnant cysts of the sulcus (Sulcus hippocampalis), are formed with incomplete involution of the embryonic hippocampal fissure during intrauterine development. The characteristic localization of the cysts is laterally at the apex of the hippocampal groove, between Cornu Ammonis and Gyrus dentatus. They do not manifest themselves in any way and are most often discovered by chance during routine MRI studies of the brain. According to some reports, they are detected in almost 25% of adults.

Hippocampus and coronavirus

Since the beginning of the spread of covid-19, doctors have noted in many recovered patients forgetfulness, anxiety, depressive mood, they often hear complaints of "fog in the head" and increased irritability.

The coronavirus that causes covid-19 is known to enter cells through receptors in the olfactory bulb (Bulbus olfactorius), resulting in symptoms such as anosmia or loss of smell.

The olfactory bulb is associated with the hippocampus, and neurodegenerative disease researchers at the Alzheimer's Association argue that it is responsible for the cognitive impairment seen in covid-19 patients, in particular short-term memory problems.

Recently, it was announced that they intend to start a large-scale study of the effects of coronavirus on the brain and the causes of cognitive decline in the near future, in which scientists from almost four dozen countries will participate - under the technical guidance and coordination of the WHO.

Read also -  Coronavirus lingers in the brain even after recovery

Diagnostics of the diseases of the hippocampus

The main methods for diagnosing diseases associated with certain damage to the structures of the hippocampus include the  study of the neuropsychic sphere , magnetic resonance imaging and  computed tomography of the brain .

Doctors prefer to visualize the hippocampus on MRI: with standard T1-weighted sagittal, coronal, diffusion-weighted axial images, T2-weighted axial images of the whole brain, and T2-weighted coronal images of the temporal lobes. To identify pathological changes in the fields of the hippocampus itself, dentate or parahippocampal gyri, 3T MRI is used; an MRI scan with a higher field may be required. [29]

Also carried out:  Doppler ultrasonography of the vessels of the brain , EEG -  encyphalography  of the brain.

Details in publications:

• Epilepsy - Diagnosis
• Depressive Disorder - Diagnosis

Treatment of diseases of the hippocampus

Congenital anomalies of the hippocampus associated with underdevelopment and reduction deformities of the brain cannot be cured: children are doomed to disability due to  cognitive impairments of  varying severity and associated behavioral disorders.

How are some of the diseases listed above treated? Read in publications:

• Epilepsy - Treatment
• Dementia in Alzheimer's Disease - Treatment
• New treatments for Alzheimer's disease
• Depression treatment
• Vitamins for the brain

In cases where anticonvulsants, that is,  antiepileptic drugs,  do not cope with seizures in mesial temporal lobe epilepsy, they  [30]resort to at least surgical treatment.

Operations include: hippocampectomy - removal of the hippocampus; limited or extended ectomy of epileptogenic zones (resection or excision of the affected structures); temporal lobectomy with preservation of the hippocampus; selective resection of the hippocampus and tonsil (amygdala-hippocampectomy). [31]

According to foreign clinical statistics, in 50-53% of cases after surgery, epileptic seizures in patients stop, 25-30% of operated patients have seizures 3-4 times a year.

How to train the hippocampus?

Since the hippocampus (its dentate gyrus) is one of the few cerebral structures where neurogenesis or nerve regeneration occurs - the formation of new neurons, the process of memory impairment (provided that the underlying disease is treated) can be positively influenced by exercise.

It has been proven that  aerobic sports exercise  and any physical activity (and especially in old age) contribute to the survival of neurons and stimulate the formation of new nerve cells in the hippocampus. By the way, exercise reduces stress and improves depression. [32],  [33], 

In addition, cognitive stimulation helps to train the hippocampus, that is, mental exercises: memorizing poetry, reading, doing crosswords, playing chess, etc.

How to enlarge the hippocampus, because in old age it becomes smaller? A proven remedy by researchers is exercise, which increases the perfusion of the hippocampus, and the formation of new cells of the nervous tissue is more active.

How to restore the hippocampus after stress? Engage in mindfulness meditation, which is a mind-training practice aimed at slowing down running thoughts, releasing negativity, and achieving peace of mind and body. A study from an East Asian university has shown that meditation can help lower blood cortisol levels.