The central nervous system (CNS) consists of the brain and spinal cord. 

Brain

The adult brain consists of four major parts: 

• Cerebrum 
• Diencephalon (Thalamus, Hypothalamus, and Epithalamus)
• Brain stem (Medulla oblongata, Pons, and Midbrain)

• Cerebellum

Fig. 1: Parts of Brain

Protection to the brand

• Cranium

• Meninges

• Blood-Brain Barrier (BBB)

• Cerebrospinal fluid (CSF)

 
Cranium

Bones of cranium includes: STEP OF 6

S : Sphenoid bone

T : Temporal bones (2)

E : Ethmoid bone

P : Parietal bones (2)

O: Occipital bone

F : Frontal bone

Fig.2: Bones of the skull

Meninges

Three connective tissue layers cover the brain and spinal cord. 

• Dura mater

• Arachnoid mater

• Pia mater

The outermost layer is the Dura mater (tough mother), composed of dense irregular connective tissue. 

Arachnoid mater, the middle meninx (singular form of meninges) is an avascular covering made up of delicate collagen fibers and some elastic fibers. 

Between the dura mater and the arachnoid mater is a thin subdural space, which contains interstitial fluid.

The innermost layer, the pia mater, is a thin transparent connective tissue made up of squamous or cuboidal cells and interlacing bundles of collagen fibers and fine elastic fibers. It adheres with the brain and contains blood vessels to supply nutrients and oxygen. 

Sub-arachnoid space is the space between the arachnoid mater and the pia mater and it contains cerebrospinal fluid (CSF) that acts as a shock absorber to the brain.

Fig. 3: Cranial meninges

Blood-Brain Barrier (BBB)

Mainly internal carotid and vertebral arteries supply blood to the brain and the internal jugular veins transport the blood back to the heart. 

BBB is composed of tight junctions that seal the endothelial cells of the capillaries of the brain and a thick basement membrane around the capillaries. 

The processes of astrocytes (a type of neuroglial cell) press up against the capillaries and provide it the properties of tight junctions.

Water-soluble substances (most ions, creatinine, and urea) cross the BBB very slowly and only lipophilic substances (alcohol, oxygen, carbon dioxide, and most anesthetic agents) can cross the BBB rapidly.

Certain diseases, inflammation, toxin, and trauma, can cause a collapse of the BBB.

Fig.4: Blood-brain barrier

Cerebrospinal fluid (CSF)

CSF is a colorless liquid that transports nutrients and oxygen to neurons and neuroglia from blood. It circulates through cavities in the brain and spinal cord and in the subarachnoid space. It also protects the brain and spinal cord from chemical and physical injuries. 

In an adult brain, the total volume of CSF is 80 to 150 mL and the rate of formation is 20 mL/hr (480 mL/day). CSF mainly contains glucose, proteins, lactic acid, urea, cations (Na+, K+, Ca2+, Mg2+), and anions (Cl- and HCO3 ). 

The CSF contributes to homeostasis in three main ways:

i. Mechanical protection: Brain floats (buoys) in CSF inside cranium and CSF serves as a shock-absorber that safeguards the delicate tissues of the brain and spinal cord. 

ii. Chemical protection: Even a minute disturbance in the environment can affect the functioning of neurons. CSF provides an optimal chemical environment for accurate neuronal working. 

iii. Circulation: CSF allows the exchange of nutrients and waste products between the blood and nervous tissue.

Formation of CSF 

Choroid plexuses, networks of blood capillaries in the walls of the ventricles, is the site of CSF generation.

Ependymal cells cover the blood vessels, generate CSF from blood plasma by filtration and secretion. 

The blood-cerebrospinal fluid barrier allows selective substances to enter the CSF and protect the brain and spinal cord from harmful substances.

Fig.5: Choroid plexuses

Circulation of CSF

Fig.6: Circulation of CSF

The CSF flows into the third ventricle from lateral ventricles through two narrow, oval openings, the interventricular foramina. The CSF then flows through the aqueduct of the midbrain (cerebral aqueduct) into the fourth ventricle. 

CSF enters the subarachnoid space through three openings in the roof of the fourth ventricle: a median aperture and the paired lateral apertures, one on each side. 

CSF then circulates in the central canal of the spinal cord and the subarachnoid space gradually reabsorbed into the blood through arachnoid villi, fingerlike extensions of the arachnoid that project into the dural venous sinuses, especially the superior sagittal sinus (fig.3).

Cerebrum

It provides the ability to read, write, speak, think, calculate, compose music, remember, plan and imagine. The cerebrum consists of 

• Outer cerebral cortex  

• Cerebral White matter with deep Gray matter nuclei 

Fig. 7: The cerebrum

Cerebral cortex (2-4 mm thick)

The cerebral cortex (rind or bark) is a region of gray matter that forms the outer rim of the cerebrum and contains billions of neurons.

Due to faster embryonic development, there are folds in the cortex. The folds or convolutions are called gyri (singular is gyrus).

There are grooves between gyri. Fissures are the deepest grooves and sulci (singular is sulcus) are shallower grooves. 

The cerebrum is divided into two cerebral hemispheres (right and left) by the longitudinal fissure.

The two cerebral hemispheres are connected internally by the corpus callosum (white matter).

Lobes of cerebrum

Each cerebral hemisphere can be further subdivided into four lobes. The lobes are named after the bones that cover them: 

• Frontal lobe

• Parietal lobe

• Temporal lobe

• Occipital lobe

Fig.8: Lobes of the cerebrum

Cerebral White Matter

The cerebral white matter consists primarily of myelinated axons in three tracts (tract is a bundle of axons located in the CNS).

i. Association tracts: axons that conduct nerve impulses between gyri in the same hemisphere.

ii. Commissural tracts: axons that conduct nerve impulses from gyri in one cerebral hemisphere to corresponding gyri in the other cerebral hemisphere.

Three important groups of commissural tracts are 

• Corpus callosum 

• Anterior commissure

• Posterior commissure

iii. Projection tracts: axons that conduct nerve impulses from the cerebrum to lower parts of the CNS (thalamus, brain stem, or spinal cord) or from lower parts of the CNS to the cerebrum.

Basal Ganglia (basal nuclei)

There are three nuclei (masses of gray matter), deep within each cerebral hemisphere, collectively called basal ganglia.

• Globus pallidus (near to thalamus)

• Putamen (near to cerebral cortex)

• Caudate nucleus

Together, the globus pallidus and putamen are referred to as the lentiform nucleus.

Together, the lentiform and caudate nuclei are known as the corpus striatum.

The basal ganglia communicate with the cerebral cortex via neural connections with nuclei of the thalamus.

Substantia nigra (midbrain) and subthalamic nuclei are functionally linked to basal ganglia.

Basal ganglia help in the initiation and termination of body movements. 

It also suppresses unwanted movements and regulates muscle tone. 

Additionally, many aspects of cortical functions are affected by basal ganglia like sensory, limbic, cognitive, and linguistic functions.

Fig.9: Basal nuclei

Limbic System

The limbic system encircles the upper part of the brain stem and the corpus callosum and forms the floor of the diencephalon. 

The main components of the limbic system are -

The limbic lobe includes the cingulate gyrus (cingul means belt), which lies above the corpus callosum, and the parahippocampal gyrus which is in the temporal lobe.

The hippocampus (seahorse) is a part of the parahippocampal gyrus that extends into the floor of the lateral ventricle.

The dentate gyrus (toothed) lies between the hippocampus and the parahippocampal gyrus.

The amygdala (almond-shaped) is made up of several groups of neurons located close to the tail of the caudate nucleus.

The septal nuclei within the septal area under the corpus callosum and the para terminal gyrus (a cerebral gyrus).

The mammillary bodies of the hypothalamus are two round masses close to the midline near the cerebral peduncles.

The anterior nucleus and the medial nucleus (nuclei of the thalamus) participate in limbic circuits. 

The olfactory bulbs are flattened bodies of the olfactory pathway that rest on the cribriform plate.

The fornix, stria terminalis, stria medullaris, medial forebrain bundle, and mammillothalamic tract are linked by bundles of interconnecting myelinated axons.

The limbic system is also called the “emotional brain” because it is crucial for the expression of a range of emotions, including pain, pleasure, affection, fear, docility, and anger. It also is associated with olfaction (smell) and memory. 

The hippocampus has a role in memory. 

Fig. 10 (a): Parts of the limbic system

Fig. 10 (b): Parts of the limbic system

The functional division of the Cerebral cortex

i. Sensory areas: involved in perception, receive sensory information

 

ii. Motor areas: regulate the voluntary movements

iii. Integrative areas: associated with more complex functions such as emotions, reasoning, memory, judgment, intelligence, will, and personality traits.

Hemispheric Lateralization

There are delicate anatomical modifications between the two hemispheres means each hemisphere specializes in the execution of certain unique functions.

Thalamus

It consists of paired oval masses of grey matter with interspersed tracts of white matter. Interthalamic adhesion joins the two halves of the thalamus.

The thalamus acts as a relay station for most sensory and motor impulses between the cerebral cortex and other parts of the CNS such as the brainstem, cerebellum, basal nuclei, and spinal cord. 

It has a role in maintaining consciousness, emotions, memory, movement regulation, sensory functions, hearing, vision, and olfaction.

Hypothalamus

The hypothalamus (hypo = under) is a small part of the diencephalon located inferior to the thalamus. 

It is composed of a dozen or so nuclei in four major regions:

• The mammillary region 

• The tuberal region  

• The supraoptic region

• The preoptic region 

Important functions of the hypothalamus include the following:

i. Control of the ANS: regulation of visceral activities, including regulation of heart rate, movement of food through the gastrointestinal tract, and contraction of the urinary bladder.

ii. Production of hormones: Hypothalamus secretes releasing hormones and inhibiting hormones and the bloodstream carries these hormones directly to the anterior lobe of the pituitary, where they stimulate or inhibit secretion of anterior pituitary hormones.

Also, axons from the paraventricular and supraoptic nuclei through the infundibulum extend into the posterior lobe of the pituitary. The cell bodies of these neurons make oxytocin or antidiuretic hormone. Their axons transport the hormones to the posterior pituitary for release.

iii. Regulation of emotional and behavioral patterns: Along with the limbic system, the hypothalamus participates in expressions of rage, aggression, pain, and pleasure, and the behavioral patterns related to sexual arousal.

iv. Regulation of eating and drinking: Through feeding center, satiety center, and thirst center.

v. Control of body temperature: The hypothalamus also functions as the body’s thermostat.

vi. Regulation of circadian rhythms: The suprachiasmatic nucleus (SCN) of the hypothalamus serves as the body’s internal biological clock because it establishes circadian (daily) rhythms, patterns of biological activity (such as the sleep-wake cycle) that occur on a circadian schedule (cycle of about 24 hours).

Epithalamus

The epithalamus (epi- = above), a small region superior and posterior to the thalamus, consists of the pineal gland and habenular nuclei. 

The pineal gland is about the size of a small pea and protrudes from the posterior midline of the third ventricle. 

The pineal gland is part of the endocrine system because it secretes the hormone melatonin. Melatonin helps regulate circadian rhythms.

The habenular nuclei are involved in olfaction, especially emotional responses to odors such as a loved one’s cologne or Mom’s chocolate chip cookies baking in the oven. 

Medulla Oblongata

The medulla oblongata or the medulla is continuous with the superior part of the spinal cord; it forms the inferior part of the brainstem. The medulla begins at the foramen magnum and extends to the inferior border of the pons, a distance of about 3 cm.

Some of the white matter forms bulges on the anterior aspect of the medulla. These protrusions, called the pyramids, are formed by the large corticospinal tracts that pass from the cerebrum to the spinal cord. 

Just superior to the junction of the medulla with the spinal cord, 90% of the axons in the left pyramid cross to the right side, and 90% of the axons in the right pyramid cross to the left side. This crossing is called the decussation of pyramids (decuss = crossing) and that is why each side of the brain controls voluntary movements on the opposite side of the body.

The medulla also contains several nuclei that control vital body functions.

i. Cardiovascular center regulates the rate and force of the heartbeat and the diameter of blood vessels.

  

ii. Respiratory center adjusts the basic rhythm of breathing.

iii. Vomiting center of the medulla causes vomiting, the forcible expulsion of the contents of the upper gastrointestinal (GI) tract through the mouth.  

iv. Deglutition center promotes deglutition (swallowing) of a mass of food that has moved from the oral cavity of the mouth into the pharynx (throat). 

v. Inferior olivary nucleus provides instructions that the cerebellum uses to make adjustments to muscle activity while learning new motor skills. 

vi. Gracile nucleus and cuneate nucleus are associated with sensations of touch, pressure, vibration, and conscious proprioception.

vii. Gustatory nucleus receives gustatory input from the taste buds of the tongue.

viii. Cochlear nuclei receive auditory input from the cochlea of the inner ear.

 

ix. Vestibular nuclei receive sensory information associated with equilibrium from proprioceptors (receptors that provide information regarding body position and movements) in the vestibular apparatus of the inner ear.

 

x. The medulla also contains nuclei associated with the following five pairs of cranial nerves

• Vestibulocochlear nerves (VIII) (related to hearing)

• Glossopharyngeal nerves (IX) (related to taste, swallowing, and salivation)

• Vagus nerves (X) 

• Accessory nerves (XI) (cranial portion).

• Hypoglossal nerves (XII) (related to tongue movement)

Pons

The pons (= bridge) lies directly superior to the medulla and anterior to the cerebellum and is about 2.5 cm (1 in.) long. The pons is a bridge that connects parts of the brain and the medulla, the pons consists of both nuclei and tracts.

The pons has two major structural components: 

a ventral region 

a dorsal region

The ventral region of the pons forms a large synaptic relay station consisting of scattered gray centers called the pontine nuclei. Entering and exiting these nuclei are numerous white matter tracts, each of which provides a connection between the cerebral cortex hemisphere and that of the opposite hemisphere of the cerebellum. 

The dorsal region of the pons contains the pontine respiratory group that helps control breathing.

The pons also contains nuclei associated with the following four pairs of cranial nerves.

• Trigeminal nerves (V) (regulate chewing) 

• Abducens nerves (VI) (regulate eyeball movement)

• Facial nerves (VII) (regulate the secretion of saliva and tears and control facial expression)

• Vestibulocochlear nerves (VIII) (maintain balance and equilibrium)

Midbrain

The midbrain or mesencephalon extends from the pons to the diencephalon and is about 2.5 cm (1 in.) long.  Like the medulla and the pons, the midbrain contains both nuclei and tracts.

The anterior part of the midbrain contains paired bundles of axons known as the cerebral peduncles (= little feet). The cerebral peduncles consist of axons of the corticospinal, corticobulbar, and corticopontine tracts, which conduct nerve impulses from motor areas in the cerebral cortex to the spinal cord, medulla, and pons, respectively.

The posterior part of the midbrain called the tectum (= roof), contains four rounded elevations. The two superior elevations, nuclei known as the superior colliculi (singular is colliculus), and two inferior elevations, called the inferior colliculi. 

The superior colliculi serve as reflex centers for certain visual activities such as elicit eye movements for tracking moving images (a moving car) and scanning stationary images (as you are doing to read this sentence). The superior colliculi are also responsible for reflexes that govern movements of the head, eyes, and trunk in response to visual stimuli. 

The inferior colliculi, are also reflex centers for the startle reflex, sudden movements of the head, eyes, and trunk that occur when you are surprised by a loud noise such as a gunshot.

The midbrain contains several other nuclei, including the left and right substantia nigra (substance black) which are large and darkly pigmented. Neurons that release dopamine, extending from the substantia nigra to the basal nuclei, help control subconscious muscle activities. Loss of these neurons is associated with Parkinson’s disease. 

Also present are the left and right red nuclei, which look reddish due to their rich blood supply and an iron-containing pigment in their neuronal cell bodies. Axons from the cerebellum and cerebral cortex form synapses in the red nuclei, which help control muscular movements. 

Still, other nuclei in the midbrain are associated with two pairs of cranial nerves.

• Oculomotor nerves (III) (regulate eyeball movement with constriction of pupil and change in the shape of the lens)

• Trochlear nerves (IV) (regulate the movement of the eyeball) 

Reticular Formation

Much of the brainstem consists of small clusters of neuronal cell bodies (gray matter) interspersed among small bundles of myelinated axons (white matter). The broad region where white matter and gray matter exhibit a netlike arrangement is known as the reticular formation.

It extends from the superior part of the spinal cord, throughout the brainstem, and into the inferior part of the diencephalon. 

The ascending portion of the reticular activating system (RAS) consists of sensory axons that project to the cerebral cortex, both directly and through the thalamus.

The most important function of the RAS is 

• Consciousness, a state of wakefulness in which an individual is fully alert, aware, and oriented. 

• Maintaining attention and alertness (concentrating on a single object or thought). 

• Prevents sensory overload (excessive visual and/or auditory stimulation) by filtering out insignificant information so that it does not reach consciousness.

The descending portion of the RAS has connections to the cerebellum and spinal cord and helps regulate muscle tone. This portion of the RAS also assists in the regulation of heart rate, blood pressure, and respiratory rate.

While, the RAS receives input from the eyes, ears, and other sensory receptors, there is no input from receptors for the sense of smell. Therefore, even strong odors may fail to cause arousal. People who die in house fires usually succumb to smoke inhalation without awakening. 

Cerebellum

The cerebellum occupies the inferior and posterior aspects of the cranial cavity and is positioned posterior to the medulla and pons and inferior to the posterior portion of the cerebrum. 

Like the cerebrum, the cerebellum has a highly folded surface that greatly increases the surface area of its outer gray matter cortex, allowing for a greater number of neurons. The cerebellum accounts for about a tenth of the brain mass yet contains nearly half of the neurons in the brain.

A deep groove known as the transverse fissure separates the cerebellum from the cerebrum.

Each hemisphere consists of lobes separated by deep and distinct fissures. 

The anterior lobe and posterior lobe govern subconscious aspects of skeletal muscle movements. 

The flocculonodular lobe (flocculo- = wool-like tuft) on the inferior surface contributes to equilibrium and balance.

The cerebellum's superficial layer, called the cerebellar cortex, consists of gray matter in a series of slender, parallel folds called folia (= leaves). Deep to the gray matter are tracts of white matter called arborvitae (= tree of life) that resemble branches of a tree. 

Three paired cerebellar peduncles attach the cerebellum to the brainstem. These bundles of white matter consist of axons that conduct impulses between the cerebellum and other parts of the brain. 

The superior cerebellar peduncles contain axons that extend from the cerebellum to the red nuclei of the midbrain and several nuclei of the thalamus.

The middle cerebellar peduncles are the largest; their axons carry impulses for voluntary movements from the pontine nuclei into the cerebellum. 

The inferior cerebellar peduncles consist of 

• axons of the spinocerebellar tracts that carry sensory information into the cerebellum from proprioceptors in the trunk and limbs 

• axons from the vestibular apparatus of the inner ear and from the vestibular nuclei of the medulla and pons that carry sensory information into the cerebellum from proprioceptors in the head

• axons from the inferior olivary nucleus of the medulla that enter the cerebellum and regulate the activity of cerebellar neurons

 

• axons that extend from the cerebellum to the vestibular nuclei of the medulla and pons

• axons that extend from the cerebellum to the reticular formation.

The primary functions of the cerebellum

• To evaluate how well movements initiated by motor areas in the cerebrum are being carried out. When movements initiated by the cerebral motor areas are not being carried out correctly, the cerebellum detects the discrepancies. It then sends feedback signals to motor areas of the cerebral cortex, via its connections to the thalamus. The feedback signals help correct the errors, smooth the movements, and coordinate complex sequences of skeletal muscle contractions.

 

• The cerebellum regulates posture and balance. These aspects of cerebellar function make possible all skilled muscular activities, from catching a baseball to dancing to speaking. 

• The cerebellum also processes sensory information.

Acknowledgments: 

The images were created on www.biorender.com

Image by Anne Nygård. https://images.unsplash.com/photo-1582380595031-ef1b29d7fa05?ixid=MnwxMjA3fDB8MHxwaG90by1wYWdlfHx8fGVufDB8fHx8&ixlib=rb-1.2.1&auto=format&fit=crop&w=334&q=80

Image by Anne Nygård. https://images.unsplash.com/photo-1582380626754-bcf3185f1832?ixid=MnwxMjA3fDB8MHxwaG90by1wYWdlfHx8fGVufDB8fHx8&ixlib=rb-1.2.1&auto=format&fit=crop&w=750&q=80

References:

Tortora, Gerard J., and Bryan H. Derrickson. Principles of anatomy and physiology. John Wiley & Sons, 2018.