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As a person grows older, the lens grows larger and thicker and becomes far less elastic, partly because of progressive denaturation of the lens proteins.
The ability of the lens to change shape decreases with age. The power of accommodation decreases from about 14 diopters in a child to less than 2 diopters by the time a person reaches 45 to 50 years; it then decreases to essentially 0 diopters at age 70 years. Thereafter, the lens remains almost totally non accommodating, a condition known as “presbyopia.”
Once a person has reached the state of presbyopia, each eye remains focused permanently at an almost constant distance; this distance depends on the physical characteristics of each person’s eyes. The eyes can no longer accommodate for both near and far vision.
To see clearly both in the distance and nearby, an older person must wear bifocal glasses with the upper segment focused for far-seeing and the lower segment focused for near-seeing (e.g., for reading).

Schizophrenia—Possible Exaggerated Function of Part of the Dopamine System

Schizophrenia comes in many varieties. One of the most common types is seen in the person who hears voices and has delusions of grandeur, intense fear, or other types of feelings that are unreal. Many schizophrenics
(1) are highly paranoid, with a sense of persecution from outside sources; (2) may develop incoherent speech, dissociation of ideas, and abnormal sequences of thought; and (3) are often withdrawn, sometimes with abnormal posture and even rigidity.

There are reasons to believe that schizophrenia results from one or more of three possibilities: (1) multiple areas in the cerebral cortex prefrontal lobes in which neural signals have become blocked or where processing of the signals becomes dysfunctional because many synapses normally excited by the neurotransmitter glutamate lose their responsiveness to this transmitter; (2) excessive excitement of a group of neurons that secrete dopamine in the behavioral centers of the brain, including in the frontal lobes; and/or (3) abnormal function
of a crucial part of the brain’s limbic behavioral control system centered around the hippocampus. The reason for believing that the prefrontal lobes are involved in schizophrenia is that a schizophrenic-like pattern of mental activity can be induced in monkeys by making multiple minute lesions in widespread areas of the prefrontal lobes. Dopamine has been implicated as a possible cause of schizophrenia because many patients with Parkinson’s disease develop schizophrenic-like symptoms when they are treated with the drug called L-dopa. This drug releases dopamine in the brain, which is advantageous for treating Parkinson’s disease, but at the same time it depresses various portions of the prefrontal lobes and other related areas. It has been suggested that in schizophrenia excess dopamine is secreted by a group of dopamine-secreting neurons whose cell bodies lie in the ventral tegmentum of the mesencephalon, medial and superior to the substantia nigra. These neurons give rise to the so-called mesolimbic dopaminergic system that projects nerve fibers and dopamine secretion into the medial and anterior portions of the limbic system, especially into the hippocampus, amygdala, anterior caudate nucleus, and portions of the prefrontal lobes. All of these are powerful behavioral control centers. An even more compelling reason for believing that schizophrenia might be caused by excess production of dopamine is that many drugs that are effective in treating schizophrenia—such as chlorpromazine, haloperidol, and thiothixene—-all either decrease secretion of
dopamine at dopaminergic nerve endings or decrease the effect of dopamine on subsequent neurons. Finally, possible involvement of the hippocampus in schizophrenia was discovered recently when it was learned that in schizophrenia, the hippocampus is often reduced in size, especially in the dominant hemisphere.

Slow-Wave Sleep and REM Sleep (Paradoxical Sleep, Desynchronized Sleep)

Slow-Wave Sleep
Most of us can understand the characteristics of deep slow-wave sleep by remembering the last time we were kept awake for more than 24 hours and then the deep sleep that occurred during the first hour after going to sleep.This sleep is exceedingly restful and is associated with decrease in both peripheral vascular tone and many other vegetative functions of the body. For instance,
there are 10 to 30 per cent decreases in blood pressure, respiratory rate, and basal metabolic rate. Although slow-wave sleep is frequently called “dreamless sleep,” dreams and sometimes even nightmares do occur during slow-wave sleep. The difference between the dreams that occur in slow-wave sleep and those that occur in REM sleep is that those of REM sleep are associated with more bodily muscle activity, and the dreams of slow-wave sleep usually are not remembered.
That is, during slow-wave sleep, consolidation of the dreams in memory does not occur.

REM Sleep (Paradoxical Sleep, Desynchronized Sleep)
In a normal night of sleep, bouts of REM sleep lasting 5 to 30 minutes usually appear on the average every 90 minutes.When the person is extremely sleepy, each bout of REM sleep is short, and it may even be absent. Conversely, as the person becomes more rested through the night, the durations of the REM bouts increase.
There are several important characteristics of REM
1. It is usually associated with active dreaming and active bodily muscle movements.
2. The person is even more difficult to arouse by sensory stimuli than during deep slow-wave sleep, and yet people usually awaken spontaneously in the morning during an episode of REM sleep.
3. Muscle tone throughout the body is exceedingly depressed, indicating strong inhibition of the spinal muscle control areas.
4. Heart rate and respiratory rate usually become irregular, which is characteristic of the dream state.
5. Despite the extreme inhibition of the peripheral muscles, irregular muscle movements do occur.
These are in addition to the rapid movements of the eyes.
6. The brain is highly active in REM sleep, and overall brain metabolism may be increased as
much as 20 per cent. The electroencephalogram (EEG) shows a pattern of brain waves similar to those that occur during wakefulness. This type of sleep is also called paradoxical sleep because it is a paradox that a person can still be asleep despite marked activity in the brain.
In summary, REM sleep is a type of sleep in which the brain is quite active. However, the brain activity is not channeled in the proper direction for the person to be fully aware of his or her surroundings, and therefore the person is truly asleep.

Brain Waves

Electrical recordings from the surface of the brain or even from the outer surface of the head demonstrate that there is continuous electrical activity in the brain.
Both the intensity and the patterns of this electrical activity are determined by the level of excitation of different parts of the brain resulting from sleep, wakefulness, or brain diseases such as epilepsy or even psychoses. The undulations in the recorded electrical potentials, are called brain waves, and the entire record is called an EEG (electroencephalogram).

The intensities of brain waves recorded from the surface of the scalp range from 0 to 200 microvolts, and their frequencies range from once every few seconds to 50 or more per second. The character of the waves is dependent on the degree of activity in respective parts of the cerebral cortex, and the waves change markedly between the states of wakefulness and sleep and coma. Much of the time, the brain waves are irregular, and no specific pattern can be discerned in the EEG. At other times, distinct patterns do appear, some of which are characteristic of specific abnormalities of the brain such as epilepsy,

In normal healthy people, most waves in the EEG can be classified as alpha, beta, theta, and delta waves, which are

Alpha waves are rhythmical waves that occur at frequencies between 8 and 13 cycles per second and are found in the EEGs of almost all normal adult people when they are awake and in a quiet, resting state of cerebration.These waves occur most intensely in the occipital
region but can also be recorded from the parietal and frontal regions of the scalp. Their voltage usually is about 50 microvolts. During deep sleep, the alpha waves disappear. When the awake person’s attention is directed to some specific type of mental activity, the alpha waves
are replaced by asynchronous, higher-frequency but lower-voltage beta waves.visual sensations

Beta waves occur at frequencies greater than 14 cycles per second and as high as 80 cycles per second.They are recorded mainly from the parietal and frontal regions during specific activation of these parts of the brain.

Theta waves have frequencies between 4 and 7 cycles per second. They occur normally in the parietal and temporal regions in children, but they also occur during emotional stress in some adults, particularly during disappointment and frustration. Theta waves also occur in
many brain disorders, often in degenerative brain states.

Delta waves include all the waves of the EEG with frequencies less than 3.5 cycles per second, and they often have voltages two to four times greater than most other types of brain waves. They occur in very deep sleep, in infancy, and in serious organic brain disease. They also occur in the cortex of animals that have had subcortical transections separating the cerebral cortex
from the thalamus. Therefore, delta waves can occur strictly in the cortex independent of activities in lower regions of the brain.

Introduction: Jaundice and Kernicterus

About 60% of newborn infants in the United States are jaundiced, that is they look yellow. Jaundice is the yellow coloring of the skin and other tissues. Jaundice can often be seen well in the sclera, the "whites" of the eyes, which look yellow. Many babies look jaundiced (60%), but they are not deeply jaundiced, not jaundiced below the abdomen, and they act OK - they nurse, they aren't too sleepy, they have normal muscle tone, their cry is normal, they don't arch their backs.
Kernicterus is a form of brain damage caused by excessive jaundice. The substance which causes jaundice, bilirubin, is so high that it can move out of the blood into brain tissue. When babies begin to be affected by excessive jaundice, when they begin to have brain damage, they become excessively lethargic. They are too sleepy, and they are difficult to arouse - either they don't wake up from sleep easily like a normal baby, or they don't wake up fully, or they can't be kept awake. They have a high-pitched cry, and decreased muscle tone, becoming hypotonic or floppy) with episodes of increased muscle tone (hypertonic) and arching of the head and back backwards. As the damage continues, they may develop fever, may arch their heads back into a very contorted position known as opisthotonus or retrocollis.

Special regards by


Huntington disease (HD)

Huntington's disease, chorea, or disorder (HD), is an incurable neurodegenerative genetic disorder that affects muscle coordination and some cognitive functions, typically becoming noticeable in middle age. It is the most common genetic cause of abnormal involuntary writhing movements called chorea. It is much more common in people of Western Europe descent than in those from Asia or Africa. The disease is caused by a dominant mutation on either of the two copies of a specific gene, located on an autosomal chromosome. Any child of an affected parent has a 50% chance of inheriting the disease. In rare situations where both parents have an affected gene, or either parent has two affected copies, this chance is greatly increased. Physical symptoms of Huntington's disease can begin at any age from infancy to old age, but usually begin between 35 and 44 years of age. On rare occasions, when symptoms begin before about 20 years of age, they progress faster and vary slightly, and the disease is classified asjuvenile, akinetic-rigid or Westphal variant HD.
The Huntingtin gene normally provides the genetic code for a protein that is also called "huntingtin". The mutation of the Huntingtin gene codes for a different form of the protein, whose presence results in gradual damage to specific areas of the brain. The exact way this happens is not fully understood. Genetic testing, which has been possible since the discovery of the mutation, can be performed before the onset of symptoms in the relatives of an affected individual, as an antenatal test, and also on test-tube embryos, raising ethical debates. Genetic counseling has developed to inform and aid individuals considering genetic testing and has become a model for othergenetically dominant diseases.
The exact way HD affects an individual varies and can differ even between members of the same family, but the symptoms progress predictably for most individuals. The earliest symptoms are a general lack of coordination and an unsteady gait. As the disease advances, uncoordinated, jerky body movements become more apparent, along with a decline in mental abilities and behavioral and psychiatric problems. Physical abilities are gradually impeded until coordinated movement becomes very difficult, and mental abilities generally decline into dementia. Although the disorder itself is not fatal, complications such as pneumonia, heart disease, and physical injury from falls reduce life expectancy to around twenty years after symptoms begin. There is no cure for HD, and full-time care is often required in the later stages of the disease, but there are emerging treatments to relieve some of its symptoms.
Self-help support organizations, first founded in the 1960s and increasing in number, have been working to increase public awareness, to provide support for individuals and their families, and to promote research. These organizations were instrumental in finding the gene in 1993. Since that time there have been important discoveries every few years and understanding of the disease is improving. Current research directions include determining the exact mechanism of the disease, improving animal models to expedite research, clinical trials of pharmaceuticals to treat symptoms or slow the progression of the disease, and studying procedures such as stem cell therapy with the goal of repairing damage caused by the disease.

Definition of Circadian Rhythm

Definition: The natural pattern of physiological and behavioral processes that are timed to a near 24-hour period. These processes include sleep-wake cycles, body temperature, blood pressure, and the release of hormones. This activity is controlled by the biological clock, which is located in the suprachiasmatic nuclei of the hypothalamus in human brains. It is highly influenced by natural dark-light cycles, but will persist under constant environmental conditions.

Examples: Disruptions to the circadian rhythm can cause problems with the sleep-wake cycle.

The Limbic System

The limbic system is a complex set of structures that lies on both sides of the thalamus, just under the cerebrum. It includes the hypothalamus, the hippocampus, the amygdala, and several other nearby areas. It appears to be primarily responsible for our emotional life, and has a lot to do with the formation of memories. In this drawing, you are looking at the brain cut in half, but with the brain stem intact. The part of the limbic system shown is that which is along the left side of the thalamus (hippocampus and amygdala) and just under the front of the thalamus (hypothalamus):


The hypothalamus is a small part of the brain located just below the thalamus on both sides of the third ventricle. (The ventricles are areas within the cerebrum that are filled with cerebrospinal fluid, and connect to the fluid in the spine.) It sits just inside the two tracts of the optic nerve, and just above (and intimately connected with) the pituitary gland.

The hypothalamus is one of the busiest parts of the brain, and is mainly concerned with homeostasis. Homeostasis is the process of returning something to some “set point.” It works like a thermostat: When your room gets too cold, the thermostat conveys that information to the furnace and turns it on. As your room warms up and the temperature gets beyond a certain point, it sends a signal that tells the furnace to turn off.

The hypothalamus is responsible for regulating your hunger, thirst, response to pain, levels of pleasure, sexual satisfaction, anger and aggressive behavior, and more. It also regulates the functioning of the autonomic nervous system (see below), which in turn means it regulates things like pulse, blood pressure, breathing, and arousal in response to emotional circumstances.

The hypothalamus receives inputs from a number of sources. From the vagus nerve, it gets information about blood pressure and the distension of the gut (that is, how full your stomach is). From the reticular formation in the brainstem, it gets information about skin temperature. From the optic nerve, it gets information about light and darkness. From unusual neurons lining the ventricles, it gets information about the contents of the cerebrospinal fluid, including toxins that lead to vomiting. And from the other parts of the limbic system and the olfactory (smell) nerves, it gets information that helps regulate eating and sexuality. The hypothalamus also has some receptors of its own, that provide information about ion balance and temperature of the blood.

In one of the more recent discoveries, it seems that there is a protein called leptin which is released by fat cells when we overeat. The hypothalamus apparently senses the levels of leptin in the bloodstream and responds by decreasing appetite. It would seem that some people have a mutation in a gene which produces leptin, and their bodies can’t tell the hypothalamus that they have had enough to eat. However, many overweight people do not have this mutation, so there is still a lot of research to do!

The hypothalamus sends instructions to the rest of the body in two ways. The first is to the autonomic nervous system. This allows the hypothalamus to have ultimate control of things like blood pressure, heartrate, breathing, digestion, sweating, and all the sympathetic and parasympathetic functions.

The other way the hypothalamus controls things is via the pituitary gland. It is neurally and chemically connected to the pituitary, which in turn pumps hormones called releasing factors into the bloodstream. As you know, the pituitary is the so-called “master gland,” and these hormones are vitally important in regulating growth and metabolism.


The hippocampus consists of two “horns” that curve back from the amygdala. It appears to be very important in converting things that are “in your mind” at the moment (in short-term memory) into things that you will remember for the long run (long-term memory). If the hippocampus is damaged, a person cannot build new memories, and lives instead in a strange world where everything they experience just fades away, even while older memories from the time before the damage are untouched! This very unfortunate situation is fairly accurately portrayed in the wonderful movie Memento, as well as in a more light-hearted movie, 50 First Dates. But there is nothing light-hearted about it: Most people who suffer from this kind of brain damage end up institutionalized.

The amygdalas are two almond-shaped masses of neurons on either side of the thalamus at the lower end of the hippocampus. When it is stimulated electrically, animals respond with aggression. And if the amygdala is removed, animals get very tame and no longer respond to things that would have caused rage before. But there is more to it than just anger: When removed, animals also become indifferent to stimuli that would have otherwise have caused fear and even sexual responses.

Related areas

Besides the hypothalamus, hippocampus, and amygdala, there are other areas in the structures near to the limbic system that are intimately connected to it:

The cingulate gyrus is the part of the cerebrum that lies closest to the limbic system, just above the corpus collosum. It provides a pathway from the thalamus to the hippocampus, seems to be responsible for focusing attention on emotionally significant events, and for associating memories to smells and to pain.

The ventral tegmental area of the brain stem (just below the thalamus) consists of dopamine pathways that seem to be responsible for pleasure. People with damage here tend to have difficulty getting pleasure in life, and often turn to alcohol, drugs, sweets, and gambling.
The basal ganglia (including the caudate nucleus, the putamen, the globus pallidus, and the substantia nigra) lie over and to the sides of the limbic system, and are tightly connected with the cortex above them. They are responsible for repetitive behaviors, reward experiences, and focusing attention. If you are interested in learning more about the basal ganglia, click here.
The prefrontal cortex, which is the part of the frontal lobe which lies in front of the motor area, is also closely linked to the limbic system. Besides apparently being involved in thinking about the future, making plans, and taking action, it also appears to be involved in the same dopamine pathways as the ventral tegmental area, and plays a part in pleasure and addiction.

Reticular Activating System

Reticular Formation
forms most of the core of the brainstem
reticular formation is made up of heterogeneous neurons that have different functions, but do not form distinct nuclei
raphe nuclei – located along midline of brainstem and release serotonin;
substantia nigra (DOPA) and locus coeruleus (NEpi) – also considered part of the reticular formation
Anatomy of the Reticular Formation

Neurons: reticular means ‘net’; this refers to highly branched nature of the axons and dendrites of the reticular formation
dendrites: mostly oriented in the transverse plane; act like antennae to pick up signals travelling up and down
axons: also highly branched; neurons send signals up and down
Chemoanatomy: many new neurotransmitters are still being discovered, but some generalizations can be made
cells in the medial group are cholinergic and/or cholinoceptive
many raphe neurons contains serotonin; also substance P, and TRH; thought to regulate selective attention
locus coeruleus neurons are all noradrenergic; has a part in the sleep/wake cycle
Afferent Connections: reticular formation neruons get signals from many sensory modalities at once
spinoreticular fibers: sensory input of all the modalities from the spinal cord
cranial nerve sensory nuclei project second order neurons to the reticular formation
cerebellar fibers: mostly from the fastigal nucleus; project to 2/3 of the reticular formation
corticoreticular fibers: descending fibers parallel to the corticospinal; mostly from the sensorimotor cortex
Efferent Connections:
descending reticulospinal fibers: run from reticular formation to spinal cord where they activate motor pathways
ascending fibers go to: thalamus, hypothalamus, preoptic area, medial septal nucleus, striatum, and other structures, some branches go as far forward as the forebrain
collateral branches of the reticular formation are found in all cranial nerve nuclei
many efferent axons branch to make both ascending and descending branches
ascending fibers generally are more caudal, descending are generally more rostral; this allows for the integration of ascending and descending signals
note on sensory systems: sensory info travels in two parallel paths (experimental evidence in physiology section below)
specific sensory sytems: the classical paths (i.e. DCML); go directly to the thalamus
thalamic efferents project to specific targets in the cortex
this system is concerned with recognition and processing of stimuli (i.e. recognizing sounds)
reticular sensory systems: parallel to the classical path, but the second order neurons go first to the reticular formation, where they synapse and efferent fibers are sent from the reticular formation to parts of the thalamus that are distinct from the specific system (mainly the intralaminar nuclei)
thalamic efferents project diffusely to the cortex
this system is evolutionarily older and is concerned with quick response to important and appropriate stimuli (i.e. bringing the cortex up to full speed when you hear a tiger bearing down on your ass)
control of the sensitivity of this system is important Þ oversensitivity can lead to panic disorder in which normally mild stimulus leads to an inappropriate response (i.e. intense fear evoked by a benign sound)
Reticular Activating System: a subset of the reticular formation concerned with consciousness
during sleep and drowsiness: EEG shows high amplitude, low frequency waves (synchronized waves)
during waking and alertness: EEG shows low amplitude, high frequency waves (desynchronized waves)
note: desynchronized is really a misnomer; synchrony is present, just not as obvious
the transition between the two is termed activation; controlled by the reticular activating system
theory: thalamus and cortex communicate in a loop and this accounts for the slow waves during sleep; during conciousness, other inputs modulate this communication leading to the desynchronized waves
Physiology of the Reticular Activating System

Moruzzi and Magoun (1949): stimulated reticular formation of anesthetized cats Þ EEG changes identical to arousal
reticular formation stimulation mimicked effects of sensory stimulation (which also lead to desynchronized EEG)
sensory stimulation no longer resulted in arousal if the reticular formation was destroyed
arousal could still be obtained from reticular formation stimulation even if the ascending sensory structures or the corresponding sensory cortex were destroyed
conclusion: arousal to sensory stimuli is mediated by an intervening system between the ascending paths and cortex Þ Reticular Activating System
The Midbrain Reticular Formation (MRF)the primary source for EEG changes evoked by the reticular activating system
evidence: MRF fibers begin discharging at a high rate just before EEG becomes dissynchronous on arousal
midbrain RF neurons have ipsilateral ascending projections to the midline and intralaminar cell groups of the thalamus
afferent and efferent connections are somatotopically organized
most MRF neurons are mulitmodal and map to a point on the body
topography is maintained in the reticulothalamic projections
it is thought that the MRF acts as a gate, allowing only certain sensory stimuli to reach the cortex; selective attention arises from inhibition or facilitation of thalamocortical responses to a given stimulus


The cerebrum is the largest, most prominent part of the human brain. The longitudinal fissure partitions the cerebrum into right and left hemispheres, which are each separated into four lobes:

The cerebrum consists of the cerebral cortex (outer gray matter) and white matter.

The cerebral cortex is configured into convolutions (folds) that maximize surface area. It is functionally divided into three parts:

The motor cortex controls movement of voluntary muscles
The sensory cortex receives incoming information from visual, hearing, pressure, and touch receptors, and so on
The association cortex interprets incoming sensory information and is the site of intellect, memory, language, and emotion
The interior white matter consists of myelinated axons of neurons that link several regions of the brain. These axons are arranged into bundles (tracts) connecting the following:

Neurons within the same hemisphere bundles (tracts)
Right and left hemispheres
The cerebrum with other components of the brain and spinal cord


Q-1 What is the difference btw Basal ganglia and Cerebellum?

Ans:Basal Ganglia:
2-Emotions works in relationship with Limbic system
3-Recognition and performance (movements) "brake hypothesis"

1-The cerebellum is involved in the coordination of movement
2-The cerebellum is also partly responsible for motor learning, such as riding a bicycle.

Q-2 Histological difference btw Cerebrum and Brain stem?

Ans:Cerebral cortex contain Non-spiny simple neurons (non-myelinated) 20% Sensory neurons 28% Motor neurons
Basal ganglia contain Spiny motor neurons (Myelinated) 80% Motor neurons 20% sensory neurons

Q-3 Neurological Disorders

Ans: Cerebrum: ALzheimer's disease(formation of plaques)(Dimentia)
Thalamus: Asphasia, lesions lead to loss of all sensation,astereognosis
Basal ganglia:Parkinsons disease,Huntingtons Cholera
Ataxia(lack of order)

Reeling, wide-based gait

Decomposition of movement

Inability to correctly sequence fine, coordinated acts


Inability to articulate words correctly, with slurring and inappropriate phrasing


Inability to perform rapid alternating movements

Dysmetria(lack of measurement)

Inability to control range of movement


Decreased muscle tone


Involuntary, rapid oscillation of the eyeballs in a horizontal, vertical, or rotary direction, with the fast component maximal toward the side of the cerebellar lesion

Scanning speech

Slow enunciation with a tendency to hesitate at the beginning of a word or syllable


Rhythmic, alternating, oscillatory movement of a limb as it approaches a target (intention tremor) or of proximal musculature when fixed posture or weight bearing is attempted (postural tremor)


The basal ganglia and cerebellum are large collections of nuclei that modify movement on a minute-to-minute basis. Motor cortex sends information to both, and both structures send information right back to cortex via the thalamus. (Remember, to get to cortex you must go through thalamus.) The output of the cerebellum is excitatory, while the basal ganglia are inhibitory. The balance between these two systems allows for smooth, coordinated movement, and a disturbance in either system will show up as movement disorders.

A. The basal ganglia:

What are the basal ganglia? The name is confusing, as generally a ganglion is a collection of cell bodies outside the central nervous system. Blame the early anatomists. The basal ganglia are a collection of nuclei deep to the white matter of cerebral cortex. The name includes: caudate, putamen, nucleus accumbens, globus pallidus, substantia nigra, subthalamic nucleus, and historically the claustrum and the amygdala. However, the claustrum and the amygdala do not really deal with movement, nor are they interconnected with the rest of the basal ganglia, so they have been dropped from this section. Other groupings you may hear are the striatum (caudate + putamen + nucleus accumbens), the corpus striatum (striatum + globus pallidus), or the lenticular nucleus (putamen + globus pallidus), but these groupings obviously get confusing very quickly, so we will try to avoid them.

The anatomy of these structures should be a review from the "coronal and horizontal sections" lab. Here once again are the basal ganglia as they appear when stained for myelin:

rostral section:
middle section:

caudal section:

An alternate stain is the acetylcholinesterase (AChE) stain. This technique stains for the enzyme that degrades acetylcholine (ACh), a major neurotransmitter. Areas which use ACh generally stain darkly. Here is a section through monkey brain, stained for AChE.

You can see that the caudate and putamen are stained, while the globus pallidus remains fairly pale. This emphasizes their different functions and connections. And those are...?

B. Different functions and connections:

The relationships between the nuclei of the basal ganglia are by no means completely understood. When dealing with the brain, you may sometimes be tempted to think that everything is connected to everything else. Take heart, some fairly simple generalizations and schematics can be drawn.

The caudate and putamen receive most of the input from cerebral cortex; in this sense they are the doorway into the basal ganglia. There are some regional differences: for example, medial caudate and nucleus accumbens receive their input from frontal cortex and limbic areas, and are implicated more in thinking and schizophrenia than in moving and motion disorders. The caudate and putamen are reciprocally interconnected with the substantia nigra, but send most of their output to the globus pallidus (see diagram below).

The substantia nigra can be divided into two parts: the substantia nigra pars compacta (SNpc) and the substantia nigra pars reticulata (SNpr). The SNpc receives input from the caudate and putamen, and sends information right back. The SNpr also receives input from the caudate and putamen, but sends it outside the basal ganglia to control head and eye movements. The SNpc is the more famous of the two, as it produces dopamine, which is critical for normal movement. The SNpc degenerates in Parkinson's disease, but the condition can be treated by giving oral dopamine precursors.

The globus pallidus can also be divided into two parts: the globus pallidus externa (GPe) and the globus pallidus interna (GPi). Both receive input from the caudate and putamen, and both are in communication with the subthalamic nucleus. It is the GPi, however, that sends the major inhibitory output from the basal ganglia back to thalamus. The GPi also sends a few projections to an area of midbrain (the PPPA), presumably to assist in postural control.

This schematic summarizes the connections of the basal ganglia as described above.

Although there are many different neurotransmitters used within the basal ganglia (principally ACh, GABA, and dopamine), the overall effect on thalamus is inhibitory. The function of the basal ganglia is often described in terms of a "brake hypothesis". To sit still, you must put the brakes on all movements except those reflexes that maintain an upright posture. To move, you must apply a brake to some postural reflexes, and release the brake on voluntary movement. In such a complicated system, it is apparent that small disturbances can throw the whole system out of whack, often in unpredictable ways. The deficits tend to fall into one of two categories: the presence of extraneous unwanted movements or an absence or difficulty with intended movements.

C. Lesions of the basal ganglia:

Lesions in specific nuclei tend to produce characteristic deficits. One well-known disorder is Parkinson's disease, which is the slow and steady loss of dopaminergic neurons in SNpc. An instant Parkinson-like syndrome will result if these neurons are damaged. This happened several years ago to an unfortunate group of people who took some home-brewed Demerol in search of a high. It was contaminated by a very nasty byproduct, MPTP ,which selectively zapped the SNpc neurons. The three symptoms usually associated with Parkinson's are tremor, rigidity, and bradykinesia. The tremor is most apparent at rest. Rigidity is a result of simultaneous contraction of flexors and extensors, which tends to lock up the limbs. Bradykinesia, or "slow movement", is a difficulty initiating voluntary movement, as though the brake cannot be released.

Huntington's disease, or chorea, is a hereditary disease of unwanted movements. It results from degeneration of the caudate and putamen, and produces continuous dance-like movements of the face and limbs. A related disorder is hemiballismus, flailing movements of one arm and leg, which is caused by damage (i.e., stroke) of the subthalamic nucleus.

D. The cerebellum:

The cerebellum is involved in the coordination of movement. A simple way to look at its purpose is that it compares what you thought you were going to do (according to motor cortex) with what is actually happening down in the limbs (according to proprioceptive feedback), and corrects the movement if there is a problem. The cerebellum is also partly responsible for motor learning, such as riding a bicycle. Unlike the cerebrum, which works entirely on a contralateral basis, the cerebellum works ipsilaterally.

The cerebellum ("little brain") has convolutions similar to those of cerebral cortex, only the folds are much smaller. Like the cerebrum, the cerebellum has an outer cortex, an inner white matter, and deep nuclei below the white matter.

Cat cerebellum, sagittal section
Single folium, enlarged

If we enlarge a single fold of cerebellum, or a folium, we can begin to see the organization of cell types. The outermost layer of the cortex is called the molecular layer, and is nearly cell-free. Instead it is occupied mostly by axons and dendrites. The layer below that is a monolayer of large cells called Purkinje cells, central players in the circuitry of the cerebellum. Below the Purkinje cells is a dense layer of tiny neurons called granule cells. Finally, in the center of each folium is the white matter, all of the axons traveling into and out of the folia.

These cell types are hooked together in stereotypical ways throughout the cerebellum.

Mossy fibers are one of two main sources of input to the cerebellar cortex. A mossy fiber is an axon terminal that ends in a large, bulbous swelling. These mossy fibers enter the granule cell layer and synapse on the dendrites of granule cells (right); in fact the granule cells reach out with little "claws" to grasp the terminals. The granule cells then send their axons up to the molecular layer, where they end in a T and run parallel to the surface. For this reason these axons are called parallel fibers. The parallel fibers synapse on the huge dendritic arrays of the Purkinje cells.

However, the individual parallel fibers are not a strong drive to the Purkinje cells. The Purkinje cell dendrites fan out within a plane, like the splayed fingers of one hand. If you were to turn a Purkinje cell to the side, it would have almost no width at all. The parallel fibers run perpendicular to the Purkinje cells, so that they only make contact once as they pass through the dendrites.

Although each parallel fiber touches each Purkinje cell only once, the thousands of parallel fibers working together can drive the Purkinje cells to fire like mad.

The second main type of input to the folium is the climbing fiber. The climbing fibers go straight to the Purkinje cell layer and snake up the Purkinje dendrites, like ivy climbing a trellis. Each climbing fiber associates with only one Purkinje cell, but when the climbing fiber fires, it provokes a large response in the Purkinje cell.

The Purkinje cell (left) compares and processes the varying inputs it gets, and finally sends its own axons out through the white matter and down to the deep nuclei. Although the inhibitory Purkinje cells are the main output of the cerebellar cortex, the output from the cerebellum as a whole comes from the deep nuclei. The three deep nuclei are responsible for sending excitatory output back to the thalamus, as well as to postural and vestibular centers.
There are a few other cell types in cerebellar cortex, which can all be lumped into the category of inhibitory interneuron. The Golgi cell is found among the granule cells. The stellate and basket cells live in the molecular layer. The basket cell (right) drops axon branches down into the Purkinje cell layer where the branches wrap around the cell bodies like baskets.

E. Inputs and outputs of the cerebellum:

The cerebellum operates in 3's: there are 3 highways leading in and out of the cerebellum, there are 3 main inputs, and there are 3 main outputs from 3 deep nuclei. They are:

The 3 highways are the peduncles, or "stalks". There are 3 pairs: the inferior, middle, and superior peduncles.

The 3 inputs are: Mossy fibers from the spinocerebellar pathways, climbing fibers from the inferior olive, and more mossy fibers from the pons, which are carrying information from cerebral cortex. The mossy fibers from the spinal cord have come up ipsilaterally, so they do not need to cross. The fibers coming down from cerebral cortex, however, DO need to cross (remember the cerebrum is concerned with the opposite side of the body, unlike the cerebellum). These fibers synapse in the pons (hence the huge block of fibers in the cerebral peduncles labeled "corticopontine"), cross, and enter the cerebellum as mossy fibers.

The 3 deep nuclei are the fastigial, interposed, and dentate nuclei. The fastigial nucleus is primarily concerned with balance, and sends information mainly to vestibular and reticular nuclei. The dentate and interposed nuclei are concerned more with voluntary movement, and send axons mainly to thalamus and the red nucleus.

Neurohumoral mechanism

Neurohumoral mechanism maintaining normal cardiac output and blood pressure

Acute haemorrhage —>

1) Rapidly acting pressure control mechanisms; to return blood pressure to physiological levels. All are nervous mechanisms:
i) Baroreceptor
ii) Chemoreceptor
iii) CNS ischaemic response

2) Long term mechanisms for arterial pressure regulation; to return blood volume to normal levels. Essentially involves kidney control via several hormonal mechanisms:
i) Renin — Angiotensin
ii) Aldosterone




• Baroreceptors are especially abundant in the:
a) carotid sinuses [located in wall of ICA just above carotid bifurcation]
b) walls of the aortic arch
• Impulses are transmitted from:
a) carotid sinus via the glossopharangeal nerve (CN-IX) to the medulla
b) aortic arch via the vagal nerve (CN-X) to the medulla

response of baroreceptors to pressure

• < i =" impulses]">
i) vasodilation of peripheral vasculature
ii) decreased HR & contractility
—> reduced BP
[low BP has an opposite effect]
• baroreceptors play a major role in maintaining BP during postural changes


• Chemoreceptors are located in the:
a) carotid bodies [located in the carotid bifurcation]
b) aortic bodies in walls of the aortic arch
• Impulses are transmitted via the vagus [along with nerve fibres from baroreceptors] into the vasomotor centre
• Each body has its own blood supply —> each body is in close contact with arterial blood

chemoreceptor reflex
• 1° reduced arterial BP —> reduced O2; increased CO2 & H+ —> stimulate chemoreceptors —> excite vasomotor centre —> increase BP
[& increased resp stim]
• 1°reduced O2; increased CO2 & H+ —> stimulate chemoreceptors —> excite vasomotor centre —> increase BP
• Only works strongly with BP < style="font-weight:bold;">atrial reflexes
• stretched atria —>
1) slight reflex vasodilation of peripheral arterioles —>
i) reduced peripheral resistance —> reduced BP back down to normal
ii) increased blood flow into capillaries —> increased capillary pressure —> third space shifting —> reduced blood volume
2) reflex dilatation of afferent arterioles of kidney —> increased urine production
3) stimulate hypothalamus —> decreased ADH —> reduced resorption of H2O in kidney —> increased urine secretion
4) increased HR [Bainbridge reflex] —> offload fluid from heart


• reduced blood flow to vasomotor centre in brain stem —> ischaemia of medulla —> increased local[CO2] —> excite vasomotor centre —> increased BP
• has a tremendous magnitude in increasing BP: is one of the most powerful activators of the sympathetic vasoconstrictor system
• Only becomes active at arterial BP <> compression of arteries in brain —> CNS ischaemic response —> increased BP

note that in all the above reflexes, the increased sympathetic output not only stimulates the arteries & arterioles but also constricts the veins —> increased mean systemic pressure —> increased cardiac output —> increased BP



• Sympathetic stimulation —> stimulate adrenal medulla —> release of Ad & NAd —> excite heart; vasoconstrict most blood vessels
• May act on metarterioles which are not innervated


• Reduced BP —> hypothalamus secretes vasopressin via post pituitary —> direct vasoconstriction —> increased peripheral resistance/MSFP —> increased BP
• Very potent; plays an important role in correcting BP when is acutely dangerously low —> important short term role
• Important long term role as ADH (same substance)

Decreased-BP -- RENIN

• at least 20 minutes are required before this system can become fully active
• it has a relatively long duration of action

Types of Cancer

Cancer is a group of many related diseases that begin in cells, the body's basic unit of life. Normally, cells grow and divide to produce more cells only when the body needs them. Sometimes, however, cells become abnormal and keep dividing to form more cells without control or order, creating a mass of excess tissue called a tumor. Tumors can be malignant (cancerous) or benign (not cancerous).

The cells in malignant tumors can invade and damage nearby tissue and organs. Cancer cells can also break away from a malignant tumor and travel through the bloodstream or lymphatic system to form new tumors in other parts of the body.

Most cancers are named for the organ or type of cell in which they begin. For example, cancer that begins in the lung is lung cancer, and cancer that begins in cells in the skin known as melanocytes is called melanoma.

When cancer cells spread (metastasize) from their original location to another part of the body, the new tumor has the same kind of abnormal cells and the same name as the primary tumor. For example, if lung cancer spreads to the brain, the cancer cells in the brain are actually lung cancer cells. The disease is called metastatic lung cancer (it is not brain cancer).

Use the links below to find information on specific types of cancer, including treatment options, expertise at The James, clinical trials, and frequently asked questions.

Common Cancers

Bone Cancer
Brain Cancer
Breast Cancer
Endocrine Cancer
Gastrointestinal Cancer
Gynecologic Cancer
Head & Neck Cancer
Lung Cancer
Multiple Myeloma
Prostate Cancer
Skin Cancer
Soft Tissue Sarcoma

Erectile dysfunction


Erectile dysfunction is the inability to develop and maintain an erection for satisfactory sexual intercourse or activity in the absence of an ejaculatory disorder such as premature ejaculation). Erectile dysfunction is the preferred term rather than the more commonly used term of impotence. There are no universally agreed on criteria for how consistent the problem has to be and for what duration it needs to be present to fulfill the definition. A period of persistence for longer than 3 months has been suggested as a reasonable clinical guideline.

Signs and Symptoms

Although erectile dysfunction is a common problem, many patients are reluctant to discuss it. Certainly, some patients who present with issues relating to depression or anxiety disorders may actually have a significant problem with erectile dysfunction. Additionally, patients who are poorly compliant with medication prescribed for hypertension may be experiencing significant erectile dysfunction. The best way to elicit whether the problem is present is to ask questions about sexual function as a routine part of the examination.
Some health questionnaires help screen for and evaluate erectile dysfunction and may help in the primary care setting. It is important, however, to recognize that abbreviated questionnaires may not evaluate specific areas of the sexual cycle, such as sexual desire, ejaculation, and orgasm. Nonetheless, they can be useful in helping patients discuss the problem and in signaling the need for an evaluation