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The Anatomy of the Hippocampus

November 2021

November 2021

DOI:10.36255/exonpublications.cerebralischemia.2021.hippocampus

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In book: Cerebral Ischemia (pp.17-30)
Publisher: Exon Publications, Brisbane, Australia

Authors:

Pradip Rameshbhai Chauhan

All India Institute of Medical Sciences Rajkot

Chauhan Girish Rameshbhai

Government Dental College and Hospital, Jamnagar, ગુજરાત

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The hippocampal formation is responsible for memory processing, learning , spatial navigation, and emotions. It includes the indusium griseum, longitudinal striae, gyrus fasciolaris, hippocampus proper (cornu ammonis, dentate gyrus, and subiculum) and part of the uncus. The hippocampus has the archipallial cortex and is formed by the infoldings of the dentate gyrus, cornu ammonis and subiculum. The dentate gyrus is a narrow crenated strip of grey matter. The dentate gyrus consists of three layers, from the outside in: the molecular layer, granular layer, and polymorphic layer. The granular neurons receive input from the parahippocampal gyrus (entorhi-nal cortex) via the perforant pathway. The granular neurons send mossy fibers to the apical dendrites of pyramidal cells present in the cornu ammonis. The axons of hip-pocampal pyramidal cells form a sheet of white fibers known as the alveus which continues as fimbria and fornix. The fornix projects into the septal area. From the septal area few fibers synapse into the cingulate gyrus which returns to the hippocam-pus. The neuronal intrinsic circuit, known as the Papez circuit of the hippocampus, plays a crucial role in the memory processing.

Hippocampal formation and connection of fornix. A, Schematic diagram of medial surface of the cerebral hemisphere showing dentate gyrus, cingulate gyrus, fornix, mammillary body and paraterminal gyrus. B, Formation, course, and termination of fornix.

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The hippocampus, dentate gyrus, subiculum, and entorhinal cortex. A, Coronal section through the hippocampus and dentate Gyrus; B, Schematic diagram to show the histological layers of the dentate gyrus and cornu ammonis.

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Intrinsic neuronal circuit of the hippocampal formation. A, Papez memory circuit. B, Perforant and alveolar pathway.

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(Continued) Intrinsic neuronal circuit of the hippocampal formation. C, Perforant pathway.

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In: Cerebral Ischemia. Pluta R (Editor). Exon Publications, Brisbane, Australia.

ISBN: 978-0-6450017-9-2; Doi: https://doi.org/10.36255/exonpublications.

cerebralischemia.2021

License: This open access article is licenced under Creative Commons Attribution-NonCommercial

4.0 International (CC BY-NC 4.0) https://creativecommons.org/licenses/by-nc/4.0/

Abstract: The hippocampal formation is responsible for memory processing, learn-

ing, spatial navigation, and emotions. It includes the indusium griseum, longitudinal

striae, gyrus fasciolaris, hippocampus proper (cornu ammonis, dentate gyrus, and

subiculum) and part of the uncus. The hippocampus has the archipallial cortex and is

formed by the infoldings of the dentate gyrus, cornu ammonis and subiculum. The

dentate gyrus is a narrow crenated strip of grey matter. The dentate gyrus consists of

three layers, from the outside in: the molecular layer, granular layer, and polymorphic

layer. The granular neurons receive input from the parahippocampal gyrus (entorhi-

nal cortex) via the perforant pathway. The granular neurons send mossy ﬁbers to the

apical dendrites of pyramidal cells present in the cornu ammonis. The axons of hip-

pocampal pyramidal cells form a sheet of white ﬁbers known as the alveus which

continues as ﬁmbria and fornix. The fornix projects into the septal area. From the

septal area few ﬁbers synapse into the cingulate gyrus which returns to the hippocam-

pus. The neuronal intrinsic circuit, known as the Papez circuit of the hippocampus,

plays a crucial role in the memory processing.

Keywords: ﬁmbria; fornix; hippocampus; Papez circuit; perforant pathway

The Anatomy of the Hippocampus

Pradip Chauhan1 • Kinjal Jethwa2 • Ashish Rathawa3 • Girish Chauhan4 •

Simmi Mehra1

1Department of Anatomy, All India Institute of Medical Sciences, Rajkot, Gujarat, India;

2Department of Anatomy, SKBS Medical College and Research Institute, Sumandeep

Vidhyapeeth, Baroda, Gujarat, India; 3Department of Anatomy, GMERS Medical College,

Junagadh, Gujarat, India; 4Department of Oral Pathology, Government Dental College,

Jamanagar, Gujarat, India.

Author for correspondence: Pradip Chauhan, Department of Anatomy, All India Institute

of Medical Sciences, Rajkot, Gujarat, India. Email: prajjawalitresearch@gmail.com

Cite this chapter as: Chauhan P, Jethwa K, Rathawa A, Chauhan G, Mehra S.

TheAnatomy of the Hippocampus. In: Pluta R, editor. Cerebral Ischemia. Brisbane (AU):

Exon Publications; 2021. Online ﬁrst Sep 17.

Doi: https://doi.org/10.36255/exonpublications.cerebralischemia.2021.hippocampus

Chauhan P et al.

INTRODUCTION

The hippocampus is part of the limbic lobe buried in the medial part of the tem-

poral lobe and involved in memory processing, learning, spatial navigation, and

emotions (1). The hippocampal formation (formatio hippocampi) comprises

(Figure 1) indusium griseum, longitudinal striae, gyrus fasciolaris, hippocampus

proper (cornu ammonis, dentate gyrus and subiculum) and part of the uncus

(1–3). The hippocampal formation has archipallial cortex and develops along the

inferomedial surface of cerebral hemisphere; during development, it follows the

outer border of the C-shaped choroidal ﬁssure (4). The hippocampus converts

short-term memory into long-term memory, solves spatial memory, and recollects

the past experiences of places. It also plays a pivotal role in emotions and behavior

of a person.

Figure 1. Hippocampal formation and connection of fornix. A, Schematic diagram of medial

surface of the cerebral hemisphere showing dentate gyrus, cingulate gyrus, fornix,

mammillary body and paraterminal gyrus. B, Formation, course, and termination of fornix.

Dentate gyrus

Alveus

Fimbria

Fornix Dorsal fornixVentral fornix

Crura of fornix

Body of fornix

Columns of fornix

Pre-commissural fornix

(Terminates into paraterminal gyrus)

Post-commissural

fornix

(Mammilary body)

Indusium griseum

Mammillary body

Habenular nucleus

Post-commisural ﬁbres

Pre-commisural ﬁbres

Ventral fornix

Dorsal fornix

Cingulate gyrus

Corpus callosum

Septum

pellucidum

Anterior commisure

Paraterminal gyrus

Dentate gyrus

Hippocampus

Thalamus

Hippocampal Anatomy 19

INDUSIUM GRISEUM AND LONGITUDINAL STRIAE

Indusium griseum and longitudinal striae are vestigial parts of the hippocampal

formation (5). Indusium griseum is a thin sheet of grey matter above the corpus

callosum and traversed by pairs of medial and lateral longitudinal striae on each

side of the midline (5, 6). Anteriorly, the indusium griseum continues around

thegenu and rostrum of the corpus callosum with the paraterminal gyrus (5–7).

The indusium griseum continues with the gyrus fasciolaris posteriorly around the

splenium of the corpus callosum (Figure 1) and then with the dentate gyrus (5–7).

The indusium griseum is continuous laterally with the cingulated gyrus through

the callosal sulcus (7).

DENTATE GYRUS

The dentate gyrus (Figure 2) is a narrow crenated strip of grey matter and con-

tinuation of gyrus fasciolaris along the upper surface of the parahippocampal

gyrus (8). The dentate gyrus contains archtitectorial fascia dentata that consists of

three layers (Figure 2). Superﬁcial to deep, the layers are: molecular layer, inter-

mediate granular layer, and multiform layer (8–10). The multiform layer contin-

ues with the CA4 region (hilus) of the cornu ammonis. The hilus and fascia

dentate collectively form the dentate gyrus (8, 9). The dentate gyrus is continuous

as a tail of the dentate gyrus (band of Giacomini) backwards and medially across

the uncus (8, 9). The band of Giacomini divides the uncus into two parts: the

uncinate gyrus anterior to the band of Giacomini and intralimbic gyrus posterior

to the band of Giacomini (8–11). The dentate gyrus is separated from the parahip-

pocampal gyrus by the hippocampal sulcus (8–11). Fimbria of fornix that covers

the dentate gyrus is separated from the dentate gyrus by the ﬁmbrio-dentate

sulcus (8–11).

HIPPOCAMPUS

Hippocampus is an elongated convex structure deep in the medial temporal lobe

and presents an elevation (Figures 1 and 2) along the ﬂoor of the inferior horn of

the lateral ventricle (1, 2, 4). The hippocampus has the archipallial cortex and is

formed by the infoldings of the dentate gyrus, cornu ammonis and subiculum

(1,4, 9–11). The subiculum is continuous with the six-layered neocortex (para-

hippocampal gyrus). During development, cornu ammonis and dentate gyrus are

folded into the inferior horn of the lateral ventricle at the hippocampal sulcus

(8-10); the process brings the outer molecular layers of the dentate gyrus and

subiculum close to each other (12).

The shape of the hippocampus in gross dissection looks like a seahorse

(genusHippocampus) on the basis of which the structure is termed as ‘Hippocampus’.

The hippocampus is also known as ‘Ammon’s horn’ because the C-shaped coronal

section of the hippocampus resembles ram’s horn; the term ‘Ammon’s horn is

derived from the Egyptian deity with ram’s head (2). The hippocampus is also

Chauhan P et al.

known as ‘pes hippocampi’ because its anterior bulbous extremity is marked by a

number of grooves and the feature resembles a paw of an animal (4, 11). The

alveus, a thin sheet of white matter, covers the ventricular surface of the hippo-

campus (10, 11). The axons of hippocampal pyramidal cells form the alveus; the

ﬁbers of the alveus converge at the medial margin of the hippocampus to form

ﬁmbria hippocampi (4, 10, 11). The ﬁmbria hippocampi proceed posteriorly cov-

ering the dentate gyrus and reach to the splenium of the corpus callosum; there-

after, continues with the fornix (2, 4, 10, 11). The ﬁmbrio-dentate sulcus separates

the ﬁmbria and the dentate gyrus. The ﬁmbria continues as fornix around the

thalamus separated by choroidal ﬁssure containing choroidal plexus (9–11).

Figure 2. The hippocampus, dentate gyrus, subiculum, and entorhinal cortex. A, Coronal section

through the hippocampus and dentate Gyrus; B, Schematic diagram to show the histological

layers of the dentate gyrus and cornu ammonis.

Tail of caudate nucleus

Alveus

Ammon’s horn

Hippocampus

Lateral ventricle

(Inferior horn)

Collateral eminence

Collateral sulcus

Parahippocampal gyrus

Fimbria

Stratum oriens

CA3

CA4

CA2

CA1

Pyramidal cell layer

Alveus

Dentate gyrus

Stratum moleculare

Subiculum

Parahippocampal gyrus

Subiculum

Hippocampal sulcus

Dentate gyrus

Fimbrio-dentate sulcus

Fimbria

Choroidal plexus

Stria terminalis

Stratum radiatum

Stratum

lacunosum

Hippocampal Anatomy 21

MICROSCOPIC STRUCTURE

The dentate gyrus is the input channel of the hippocampal formation. Histologically,

the dentate gyrus consists of three layers (Figure 2), from the outside in: the

molecular layer, granular layer, and polymorphic layer (13, 14). The dentate gyrus

is semilunar in shape; convexity of which is directed towards the molecular layer

while the concavity is directed towards the cornu ammonis (2, 4, 10–14).

Dendrites of the granular neurons receive input from the para-hippocampal

gyrus (entorhinal cortex) via perforant pathway (Figure 3) (1, 10, 14). The axons

of the granular neurons synapse by mossy ﬁbers with the apical dendrites of the

pyramidal cells present in the cornu ammonis. The three layers of cornu ammonis

(Figure 2) can be further subdivided into the following sublayers (9, 11, 14–17):

(i) Alveus: Efferent ﬁbers from the axons of the pyramidal cells of cornu ammo-

nis form the alveus while some axon collateral re-enters the hippocampus.

(ii) Stratum oriens: Contains a few inhibitory basket-cell interneurons; two

types of basket cells are observed in the stratum oriens. Axons and den-

drites of pyramidal cells, recurrent axon collateral, and commissural ﬁbers

traverse the stratum oriens.

(iii) Stratum pyramidalis: Forms the principal cellular component of cornu

ammonis. 10–30 layers of pyramidal cells are present in the stratum pyram-

idalis; functionally, the pyramidal cells are excitatory. The pyramidal cells

have an apex and a base; the base is directed toward the alveus while the

apex is directed towards the outer molecular layer. Alveus and ﬁmbria are

formed by the axons arising from the center of the base of pyramidal cells.

Dendrites arise from the base and apex of the pyramidal cells. The dendrites

arising from the base ramify in the stratum oriens and the basal dendrites

receive commissural ﬁbers from identical areas of the contralateral hippo-

campus. Dendrites arising from the apex extend deeper to branch profusely

and apical dendrites receive commissural ﬁbers from non-identical areas of

the contralateral hippocampus. Apical dendrites also receive afferents from

the entorhinal areas and mossy ﬁbers from the dentate gyrus. Recurrent

collateral from the neighboring pyramidal cells synapses with the apical

dendrites.

(iv) Stratum radiatum: Comprises apical dendrites of the pyramidal cells and

some stellate cells.

(v) Stratum lacunosum-moleculare: Contains axons and interneurons. Inhibitory

interneurons from the stratum lacunosum-moleculare project into the ret-

rosplenial cortex.

ORGANIZATION OF PYRAMIDAL CELLS IN HIPPOCAMPUS

Cornu ammonis of the hippocampus can be subdivided into four regions

(Figure2, 3): CA1, CA2, CA3, and CA4 (13–17). The CA1 is the largest region

and is delimited laterally by the presubiculum and medially by CA2. Most neu-

rons (90%) of CA1 are pyramidal cells (glutamatergic projection neurons) and the

Chauhan P et al.

Figure 3. Intrinsic neuronal circuit of the hippocampal formation. A, Papez memory circuit.

B,Perforant and alveolar pathway.

Hippocampus

Mammilary

body

Fimbria

Cingulate

gyrus

Fornix

nucleus of

thalamus

Papez circuit

Fimbria

Dentate gyrus

Perforant pathway

Entorhinal area

Alveolar pathway

Schaffer’s collateral

Sensory association areas

(Input for entorhinal cortex)

Mossy ﬁbres

Subiculum

Hippocampal Anatomy 23

rest (10%) are interneurons. CA2 layer is present towards the dentate gyrus

bounded laterally by the CA1 and medially by the CA3 layer. CA2 of the cornu

ammonis receives input from the supramammilary region of the hypothalamus

but lacks input mossy ﬁres from the dentate gyrus. CA3 layer is directed towards

the hilus of the dentate gyrus and is limited medially by the CA2 layer. The super-

ﬁcial most cells of the CA3 are described as CA4 by some authors. The apical

dendrites of the CA3 layer receive mossy ﬁbers from the granule cells of the den-

tate gyrus. Axons of the CA3 pyramidal cells contribute to the alveus, ﬁmbria, and

fornix. Some CA3 axons give collateral ﬁbers known as the Schaffer’s collaterals

which synapse with the dendrites of CA1 pyramidal cells. Axons from the CA1

pyramidal cells are connected to the subiculum neurons. Axons from the subicu-

lum neurons contribute to form the ﬁbers of the ﬁmbria and fornix via the alveo-

lar pathway (Figure 3).

CONNECTIONS OF HIPPOCAMPUS

The hippocampus receives afferents from the following structures (5, 17–24):

(i) Cingulate gyrus via cingulam.

(ii) The indusium griseum and septal nuclei through the fornix.

(iii) Contralateral hippocampus through the hippocampal commissure.

(iv) Outer part of the entorhinal area through the perforant pathway.

(v) Inner part of the entorhinal area and subiculum to the alveus through the

alveolar pathway.

Entorhinal

cortex

Schaffer’s

collaterals

Dentate

gyrus

Subiculum

CA3 area

CA1 area

Perforant

pathway

Figure 3. (Continued) Intrinsic neuronal circuit of the hippocampal formation. C, Perforant

pathway.

Chauhan P et al.

Efferent ﬁbers from the hippocampus (Figure 1) are connected to the following

areas through the fornix (17–24):

(i) Gyrus fasciolaris, indusium griseum, cingulate gyrus, and septal nuclei

through the ﬁbers of the dorsal fornix.

(ii) Paraterminal gyrus, pre-optic, and anterior hypothalamic nuclei through

the pre-commissural fornix.

(iii) Anterior nucleus of thalamus, hypothalamic nuclei, mammillary body

through the post-commissural ﬁbers.

(iv) Habenular nucleus via stria medullaris thalami.

FORNIX

Fornix forms efferent projection ﬁbers of the hippocampus and also comprises

commissural ﬁbers connecting the hippocampus of both sides (5, 10, 17–24).

Formation of fornix

Axons of pyramidal cells from the cornu ammonis with a major contribution from

the subicular complex forms the alveus. Alveus continues as a ﬁmbria which is

separated from the dentate gyrus by the ﬁmbrio-dentate sulcus. Continuation of

the ﬁmbria is called the fornix.

Course of fornix

Fornix is divided into dorsal fornix and ventral fornix at the splenium of the cor-

pus callosum (Figure 1). The dorsal fornix runs along with the gyrus fasciolaris

and indusium griseum surrounding the outer surface of the corpus callosum. The

ventral fornix runs forward below the splenium of the corpus callosum and

around the pulvinar of the thalamus. Ventral fornix forms a pair of crura that run

forwards and converge to form the body of the fornix. Commissural ﬁbers con-

nect the medial margins of both crura through the commissure of the fornix

( hippocampal commissures). Hippocampal commissures and the crura of the for-

nix are separated from the body of the corpus callosum by a space known as the

ventricle of the fornix.

Body of the fornix

The body of the fornix is a triangular structure having two symmetrical halves and

the apex of which is directed in front. Bilaminar septum pellucidum connects the

superior surface of the body of the fornix to the body of the corpus callosum. The

inferior surface is related to the ependymal roof of the third ventricle and the thala-

mus separated by tela choroidea (folding of pia mater containing the choroidal

plexus) and a pair of internal cerebral veins. Laterally, choroidal ﬁssure separates

thebody of the fornix from the thalamus. At the anterior interventricular foramen,

the body of the fornix diverges into a pair of columns of the fornix (Figure 1).

Hippocampal Anatomy 25

The anterior commissure separates the ﬁbers of the column into pre-commissural

fornix and post-commissural fornix. The pre-commissural fornix which mainly

contains axon ﬁbers from the CA3 pyramidal cells continues with the para-terminal

gyrus. The post-commissural fornix forms the anterior boundary of the interven-

tricular foramen and then turns downwards and backwards beneath the ependyma

of the third ventricle to reach the mammillary body.

HABENULAR NUCLEI

The habenular nuclei are pairs of nuclei located in the habenular trigone. The

habenular trigone is a depression on either side of the pineal stalk bounded by the

stria medullaris (cranio-medially), superior colliculus (caudally), and pulvinar end

of the thalamus (laterally) (4, 7, 25–28). The habenular nuclei receive afferents via

the stria medullaris thalami from the septal area (subcallosal area) and pre-optic

nuclei (hypothalamus), via stria terminalis from the amygdaloid body and via fornix

from the hippocampus (1, 4–8, 25–28). Some stria medullaris thalami ﬁbers pass

through the dorsal lamina of the pineal stalk and connect two habenular nuclei. The

commissural ﬁbers connecting two habenular nuclei are known as habenular com-

missure. The habenular nuclei send efferent ﬁbers to the interpeduncular nucleus

through the fasciculus retroﬂexus of Meynert. The interpeduncular nucleus projects

to the dorsal tegmental nucleus. Dorsal longitudinal fasciculus connects the dorsal

tegmental nucleus to the autonomic and reticular nuclei of the brainstem (1, 5, 25).

MAMMILO-TEGMENTAL TRACT

The mammilo-tegmental tract inﬂuences the brainstem and spinal cord for inte-

grated motor response (25). The mammilo-tegmental tract is a collection of effer-

ent ﬁbers from the mammillary body to the midbrain tegmental nuclei. Efferent

ﬁbers from the tegmental nuclei reach the reticular nuclei as reticulo-bulbar and

reticulo-spinal tract (26–28).

MAMMILO-THALAMIC TRACT

The mammilo-thalamic tract connects the mammillary body to the anterior

nucleus of the thalamus (25–28). The efferent ﬁbers from the anterior nucleus of

thalamus reach the cingulate gyrus. From the cingulate gyrus, some ﬁbers project

back to the hippocampus.

HIPPOCAMPAL FORMATION AND MEMORY

One of the functions of the hippocampus is converting short-term memory into

long-term memory. The long-term memory is maintained by a unidirectional

Chauhan P et al.

progression of synaptic connections through the intrinsic hippocampal circuitry

(Figure 3).

Papez circuit

Hippocampal circuitry postulated by Papez is called as ‘Papez circuit’ and is

adapted as a memory circuit. The Papez circuit is believed to be responsible for

emotional integration and for recent memory trace (1, 4, 7–10, 25–28). The Papez

circuit includes the hippocampus, ﬁmbria, fornix, mammillary body, anterior

nucleus of the thalamus and cingulate gyrus (Figure 3A). The entorhinal cortex

receives sensory information from the association areas of the frontal lobe, parietal

lobe, and temporal lobe. The information is converted into memory through the

Papez circuit.

Short-term memory (episodic memory) is facilitated by unidirectional activa-

tion of synaptic connection as follows:

(i) Activation of the entorhinal cortex (parahippocampal gyrus) by input from

the neocortex and limbic system.

(ii) Stimuli pass from the entorhinal cortex to the dentate gyrus via perforant

path and then pass through the CA3 area.

(iii) Schaffer’s collaterals from the CA3 transfer stimuli to the CA1; then CA1

efferent synapse at the subiculum.

(iv) Efferent ﬁbers from the subiculum again project back to the entorhinal

cortex.

Connections between the CA3 and dentate gyrus, and between CA1 and CA3,

lack feedback loop. Alveus, ﬁmbria, and the fornix formed by the axon ﬁbers of

the CA3 pyramidal cells and neurons of the subiculum are the major hippocampal

output. Fibers from the pre-commissural fornix (derived from the CA3) are con-

nected to the lateral septal nucleus, and ﬁbers of the post-commissural fornix

(derived from the subiculum) are connected to the mammillary bodies and the

hypothalamic nuclei.

Rapid formation of new memory

Long-term potentiation (LTP) is a mechanism for the rapid formation of new

memory. The long-term potentiation increases synaptic efﬁciency following the

high frequency activity of the pre-synaptic terminal. This mechanism involves

Schaffer’s collaterals and mossy ﬁbers of the hippocampus. This effect lasts for

many days leading to increased activity of the post-synaptic neurons. The high

frequency activity is responsible for the accumulation of the calcium ions in post-

synaptic neurons which triggers the LTP. Even though the original external stimu-

lus has stopped, the impulses are transmitted frequently from the synapses of the

hippocampal formation in the LTP.

Spatial memory

The hippocampus contains cells (place cells) encoding the spatial memory; these

cells are responsible for recalling a place and recalling a route to reach the place.

Hippocampal Anatomy 27

Sommer’s sector

Large pyramidal cells of the CA1 (an area known as Sommer’s sector) are extremely

sensitive to the oxygen lack; these cells necrose within a few minutes in compro-

mised blood supply. In a condition leading to cerebral ischemia, the subject may

lose the memory of the preceding few hours of the incident.

BLOOD SUPPLY AND DRAINAGE OF HIPPOCAMPUS

Hippocampus plays an important role in the formation of memory, and the

dysfunction of the hippocampus leads to neurological disorders likeAlzheimer’s

disease and epilepsy (1, 8, 29). Hippocampus is supplied by the branches of the

posterior cerebral artery and anterior choroidal artery (1, 8, 30).

Posterior cerebral artery

Posterior cerebral artery is the terminal branch of the basilar artery. It joins with

the posterior communicating artery to complete the circle of Willis (1, 8). The

posterior cerebral artery can be divided into four segments, and it gives three

major branches: cortical branches, postero-lateral striate branches, and posterior

choroid artery (29, 30). The second part of the posterior cerebral artery (from the

posterior communicating artery to the posterior margin of the midbrain) gives the

anterior inferior temporal artery and the anterior hippocampal-parahippocampal

artery which supply the entorhinal area (1, 29, 30). The posterior parahippocam-

pal artery arises from the posterior inferior temporal artery (branch of the poste-

rior cerebral artery). The parietooccipital arterial trunk (the branch from the

fourth part of the posterior cerebral artery) also supply the parahippocampal

gyrus and hippocampus.

Anterior choroid artery

Anterior choroid artery is the branch of the internal carotid artery. It originates

from the distal part of the internal carotid artery, just after the origin of the poste-

rior communicating artery, and runs into the subarachnoid space. The segment of

the anterior choroid artery up to the inferior horn of the lateral ventricle is known

as cisternal segment. The anterior choroid artery gives branches to form the cho-

roid plexus for the inferior horn of the lateral ventricle. In addition, the anterior

choroid artery also supplies the optic tract, the uncus, the globus pallidus, lateral

geniculate body, and the internal capsule. The perforating branches of the anterior

choroid artery supplies the amygdala and the hippocampus (1, 30).

The anterior hippocampal arteries supply the uncus and the head of the hippo-

campus, while the posterior hippocampal arteries supply the body and tail of the

hippocampus (29, 30). The anterior hippocampal arteries (branch of the anterior

inferior temporal artery) enter into the uncal sulcus and supplies the head of the

hippocampus. It emerges on the surface of the pyriform lobe and supplies to the

adjacent entorhinal area. The posterior hippocampal arteries run in the superﬁcial

course of the hippocampal sulcus; along the terminal segment, it gives longitudinal

Chauhan P et al.

large and small branches. The large branches penetrate the hippocampus and small

branches supply the margo denticulatus and ﬁmbriodentate sulcus. The longitudi-

nal branches form a rich anastomosis along the hippocampal sulcus (1, 29, 30).

The intrahippocampal arteries (deep branches) can be classiﬁed as large ven-

tral, small ventral, large dorsal, and small dorsal branches. The large ventral intra-

hippocampal arteries supply stratum lacunosum, stratum pyramidalis, molecular

layer of dentate gyrus, and CA1 and CA2 region of the cornu ammonis. The large

dorsal intrahippocampal arteries supply the granular layer of the dentate gyrus,

and CA3 and CA4 regions of the cornu ammonis. The small ventral intrahippo-

campal arteries supply the proximal part of the dentate gyrus. The small dorsal

intrahippocampal arteries (also known as straight arteries) runs into the ﬁbrio-

dentate sulcus and supplies the adjacent areas.

Venous drainage

The deep hippocampal veins (intrahippocampal veins) are two types: sulcal

intrahippocampal veins and subependymal intrahippocampal veins. The sulcus

intrahippocampal veins originate from the CA1 and CA2 areas and reaches

the superﬁcial hippocampal sulcus and receive tributaries from the stratum

moleculare. The subependymal intrahippocampal veins can be observed on the

ventricular surface of the hippocampus. The deep hippocampal veins of CA2 and

subiculum drain into the subependymal intrahippocampal veins (1, 29, 30).

Superﬁcial hippocampal veins form two longitudinal superﬁcial venous arcade to

cover the ﬁmbriodentate sulcus and the superﬁcial hippocampal sulcus. The

venous arcade of the ﬁmbriodentate sulcus receives subependymal intrahippo-

campal veins. The venous arcade of the superﬁcial hippocampal sulcus receives

deep intrahippocampal veins (29, 30). Both longitudinal superﬁcial venous

arcades unite at the anterior and posterior ends. Anterior end drains into the

inferior ventricular vein and posteriorly drain into medial atrial vein. Inferior

ventricular vein and medial atrial vein drain into the basal vein.

The blood vessels supplying the hippocampus have small calibers and are

more prone to thrombus formation. The thrombosis of the hippocampal arteries

leads to damage and death of pyramidal neurons of the hippocampus which is

characteristic for Alzheimer’s disease.

CONCLUSION

Hippocampal formation is a crucial structure for the memory processing and

emotional integration. Bilateral hippocampal damage may result in antegrade

amnesia; the condition in which the brain fails to establish new long-term

memories.

Conﬂict of Interest: The authors declare no potential conﬂicts of interest with

respect to research, authorship and/or publication of this manuscript.

included in this chapter do not violate copyright laws. Where relevant, appropriate

Hippocampal Anatomy 29

permissions have been obtained from the original copyright holder(s), and all origi-

nal sources have been appropriately acknowledged or referenced.

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Full-text available

Jun 2021

Treatment of bipolar depression poses a significant clinical challenge. Lamotrigine is one of a few efficacious drugs, however, it needs to be titrated very slowly and response can only be assessed after 10–12 weeks. With only a proportion of patients responding, an exploration of factors underlying treatment responsivity is of paramount clinical importance, as it may lead to an allocation of the drug to those most likely to respond to it. This study aimed at identifying differences in patterns of pre-treatment resting state functional connectivity (rsFC) that may underlie response to lamotrigine in bipolar depression. After a baseline MRI scan, twenty-one patients with bipolar depression were treated with lamotrigine in an open-label design; response, defined as ≥50% decrease in Hamilton Depression Rating Scale (HAMD) score, was assessed after 10–12 weeks of treatment. Twenty healthy controls had a baseline clinical assessment and scan but did not receive any treatment. Fifteen out of 21 (71%) patients responded to lamotrigine. Treatment responsivity was associated with enhanced pre-treatment rsFC of the right fronto-parietal network (FPN) and dorsal attention network (DAN) with left precuneus. The lack of treatment response was additionally characterised by reduced rsFC: of the DAN with right middle temporal gyrus; of the default mode network (DMN) with left precuneus; of the extended sensory-motor area with areas including the left hippocampus/left amygdala and left subcallosal cortex/nucleus accumbens; and of the left FPN with left inferior temporal gyrus/occipital fusiform gyrus/lateral occipital cortex. The results suggest that preserved rsFC between the FPN and DAN, the networks involved in cognitive control, and the hub of the posterior DMN, the left precuneus, may be critical for good response to lamotrigine as an add-on treatment in patients with bipolar depression. The study also suggests a more general decrease in rsFC to be related to poor treatment responsivity.

Pelvic Pain Alters Functional Connectivity Between Anterior Cingulate Cortex and Hippocampus in Both Humans and a Rat Model

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Full-text available

Jun 2021

The anterior cingulate cortex (ACC) and hippocampus (HIPP) are two key brain regions associated with pain and pain-related affective processing. However, whether and how pelvic pain alters the neural activity and connectivity of the ACC and HIPP under baseline and during social pain, and the underlying cellular and molecular mechanisms, remain unclear. Using functional magnetic resonance imaging (fMRI) combined with electrophysiology and biochemistry, we show that pelvic pain, particularly, primary dysmenorrhea (PDM), causes an increase in the functional connectivity between ACC and HIPP in resting-state fMRI, and a smaller reduction in connectivity during social exclusion in PDM females with periovulatory phase. Similarly, model rats demonstrate significantly increased ACC-HIPP synchronization in the gamma band, associating with reduced modulation by ACC-theta on HIPP-gamma and increased levels of receptor proteins and excitation. This study brings together human fMRI and animal research and enables improved therapeutic strategies for ameliorating pain and pain-related affective processing.

Hippocampal Malrotation: A Genetic Developmental Anomaly Related to Epilepsy?

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Full-text available

Apr 2021
BSRCCS

Hippocampal malrotation (HIMAL) is an increasingly recognized neuroimaging feature but the clinical correlation and significance in epilepsies remain under debate. It is characterized by rounded hippocampal shape, deep collateral, or occipitotemporal sulcus, and medial localization of the hippocampus. In this review, we describe the embryonic development of the hippocampus and HIMAL, the qualitative and quantitative diagnosis issues, and the pathological findings of HIMAL. HIMAL can be bilateral or unilateral and more on the left side. Furthermore, the relevance of HIMAL diagnosis in clinical practice, including its role in epileptogenesis and the impact on the pre-surgical decision are reviewed. Finally, the relationship between HIMAL and hippocampal sclerosis (HS) and the possible role of genetics in the etiology of HIMAL are discussed. The evidence so far suggested that HIMAL does not have a significant role in epileptogenesis or surgical decision. HIMAL could be a genetic developmental imaging feature that represents a more diffuse but subtle structural error during brain development. Many questions remain to be explored, such as possible cognitive alteration associated with HIMAL and whether HIMAL predisposes to the development of HS. Further studies using high-quality MRI, unified consensus qualitative and quantitative diagnostic criteria, and comprehensive cognitive assessment are recommended.

Time to put the mammillothalamic pathway into context

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Full-text available

Dec 2020
NEUROSCI BIOBEHAV R

The medial diencephalon, in particular the mammillary bodies and anterior thalamic nuclei, has long been linked to memory and amnesia. The mammillary bodies provide a dense input into the anterior thalamic nuclei, via the mammillothalamic tract. Lesions of the mammillary bodies, mammillothalamic tract and anterior thalamic nuclei all produce severe impairments in temporal and contextual memory, in both animal models and in patients, yet it is uncertain why these regions are critical. Mounting evidence from electrophysiological and neural imaging studies suggests that mammillothalamic projections exercise considerable distal influence over thalamo-cortical and hippocampo-cortical interactions. Here, we outline how damage to the mammillary body-anterior thalamic axis, in both patients and animal models, disrupts behavioural performance on tasks that relate to contextual (“where”) and temporal (“when”) processing. Focusing on the medial mammillary nuclei as a possible ‘theta-generator’ (through their interconnections with the ventral tegmental nucleus of Gudden) we discuss how the mammillary body-anterior thalamic pathway may contribute to the mechanisms via which the hippocampus and neocortex encode representations of experience.

Hippocampal vascularization: Proposal for a new classification

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Full-text available

Nov 2020

Background Anatomy of the hippocampal arterial supply is key to successful surgeries in this area. The goal of the current study is to present the results we obtained from our microsurgical dissections of the temporal lobe and to propose a new classification for the hippocampal arteries (HAs). Methods Fifty-six brain hemispheres were analyzed. All dissections in this study were made using 3–40× at the surgical microscope. Results The hippocampal arterial vasculature can be divided into six groups, according to their frequencies: Group A: mixed arterial vasculature originating from the anterior choroidal artery anterior choroidal artery, posterior cerebral artery (PCA), anterior infratemporal artery (AIA), and splenic artery (SA). Group B: Main origin at the temporal branches – main inferotemporal trunk, middle inferotemporal artery, posterior inferotemporal artery, AIA, or main branch of PCA. Group C: AIA as the main branch of the hippocampus. Group D: HAs originating from the main branch of PCA. Group E: A single hippocampal artery with the origin at the main branch of PCA. This single artery covered all of the structure and is named Ushimura’s artery. Group F: The hippocampal vessels arose exclusively from the parieto-occipital artery, calcarine artery (CA), and the SA. Conclusion This study proposes a new classification for the hippocampal vascularization, according to the origin of HAs. One of the groups has not yet been described in the literature – in which the HAs arise from the parieto-occipital artery, SA, and CA.

Histological, histochemical, and immunohistochemical studies of hippocampus in male New Zealand rabbits

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Jun 2020
ANAT REC

The present study aims to give detailed histomorphological features of the hippocampus of adult male New Zealand rabbits. Both histological and histochemical specimens were prepared to be examined microscopically by using a light microscope. The hippocampus appeared as C‐shaped hippocampal proper, dentate gyrus, and subiculum. The hippocampal proper subdivided along its length according to the density and size of its major constituent pyramidal cells into four distinct regions named Cornu Ammonis (CA1, CA2, CA3, and CA4). With the histochemical preparations, each of these regions consisted of five layers, stratum alveolus, stratum oriens, stratum pyramidale, stratum radiatum, and stratum lacunosum‐moleculare. The stratum pyramidale constituted the middle dark zone and contained the principal excitatory neurons and a few interneurons. Histochemically, the pyramidal neurons along all regions of the CA reacted positively to Grimelius silver impregnation, lead hematoxylin, Gomori's aldehyde fuchsin, aldehyde thionine, Gomori's chrome alum hematoxylin, and performic acid alcian blue stains. Immunohistochemically, the pyramidal neurons reacted positively to anti‐NSE antibodies. The dentate gyrus was formed of three distinct layers. The subiculum was formed of proper subiculum, presubiculum, and parasubiculum.