What are circadian rhythms?

Circadian rhythms are physical, mental, and behavioral changes that follow a 24-hour cycle.
These natural processes respond primarily to light and dark and affect most living things,
including animals, plants, and microbes. Chronobiology is the study of circadian rhythms.
One example of a light-related circadian rhythm is sleeping at night and being awake during
the day. The Average Teen Circadian Cycle image shows the circadian rhythm cycle of a
typical teen.

What are biological clocks?

Biological clocks are organisms’ natural timing devices, regulating the cycle of circadian
rhythms. They’re composed of specific molecules (proteins) that interact with cells
throughout the body. Nearly every tissue and organ contains biological clocks. Researchers
have identified similar genes in people, fruit flies, mice, plants, fungi, and several other
organisms that make the clocks’ molecular components.

What is the master clock?

A master clock in the brain coordinates all the biological clocks in a living thing, keeping the
clocks in sync. In vertebrate animals, including humans, the master clock is a group of about
20,000 nerve cells (neurons) that form a structure called the suprachiasmatic nucleus, or
SCN. The SCN is in a part of the brain called the hypothalamus and receives direct input
from the eyes.
Circadian rhythm cycle of a typical teenager. Credit: NIGMS.

The master clock coordinates biological clocks from received light. Credit: NIGMS

Does the body make and keep its own circadian rhythms?

Yes, natural factors in your body produce circadian rhythms. For humans, some of the most
important genes in this process are the Period and Cryptochrome genes. These genes code for
proteins that build up in the cell’s nucleus at night and lessen during the day. Studies in fruit
flies suggest that these proteins help activate feelings of wakefulness, alertness, and
sleepiness. However, signals from the environment also affect circadian rhythms. For
instance, exposure to light at a different time of day can reset when the body turns
on Period and Cryptochrome genes.

How do circadian rhythms affect health?

Circadian rhythms can influence important functions in our bodies, such as:

• Hormone release
• Eating habits and digestion
• Body temperature
However, most people notice the effect of circadian rhythms on their sleep patterns. The SCN
controls the production of melatonin, a hormone that makes you sleepy. It receives
information about incoming light from the optic nerves, which relay information from the
eyes to the brain. When there is less light—for example, at night—the SCN tells the brain to
make more melatonin so you get drowsy.

What factors can change circadian rhythms?

Changes in our body and environmental factors can cause our circadian rhythms and the
natural light-dark cycle to be out of sync. For example:

• Mutations or changes in certain genes can affect our biological clocks.

• Jet lag or shift work causes changes in the light-dark cycle.
• Light from electronic devices at night can confuse our biological clocks.
These changes can cause sleep disorders, and may lead to other chronic health conditions,
such as obesity, diabetes, depression, bipolar disorder, and seasonal affective disorder.

Circadian rhythm in babies

Newborns do not have a circadian rhythm developed until they are a few months old. This
can cause their sleeping patterns to be erratic in the first days, weeks, and months of their
lives. Their circadian rhythm developsTrusted Source as they adapt to the environment and
experience changes to their bodies. Babies begin to release melatonin when they are about
three months old, and the hormone cortisol develops from 2 months to 9 months old.

Toddlers and children have a fairly regulated sleep schedule once their circadian rhythm and
corresponding body functions mature. Children need about 9 or 10 hours of sleep a night.

Rhythem in teens

Teenagers experience a shift in their circadian rhythm known as sleep phase delay. Unlike in
their childhood years with early bedtimes around 8 or 9 p.m., teenagers may not get tired
until much later in the night.

Melatonin may not rise until closer to 10 or 11 p.m. or even later. That shift also results in a
teenager’s need to sleep later in the morning. Their peak sleepy hours at night are from 3 a.m.
to 7 a.m. — or may even be later — but they still need the same amount of sleep as children.

Circadian rhythm in adults

Adults should have a pretty consistent circadian rhythm if they practice healthy habits. Their
bedtimes and wake times should remain stable if they follow a fairly regular schedule and
aim for seven to nine hours of sleep every night. Adults likely get sleepy well before
midnight, as melatonin releases into their bodies. They reach their most tired phases of the
day from 2 to 4 a.m. and 1 to 3 p.m.

Older adults may notice their circadian rhythm changes with age, and they begin to go to bed
earlier than they used to and wake in the wee hours of the morning. In general, this is a
normal part of aging.

How to reset

You may experience disruptions to your circadian rhythm, but you can get it back on track.
Here are some tips for promoting a healthy 24-hour schedule:

• Try to adhere to a routine each day.

• Spend time outdoors when it’s light outside to boost your wakefulness.

• Get enough daily exercise — twenty or more minutes of aerobic exercise is generally
recommended.

• Sleep in an environment that promotes rest with proper lighting, a comfortable

temperature, and a supportive mattress.

• Avoid alcohol, caffeine, and nicotine in the evenings.

• Power down your screens well before bedtime and try engaging in something analog,
such as reading a book or meditating.

• Do not nap late in the afternoon or evening.

Sleep disorders

Sometimes alterations to your circadian rhythm may be the sign of a more serious condition
like a circadian rhythm sleep disorder. Two of these disorders are advanced sleep phase
and delayed sleep phase. You may be more susceptible to these if you work an irregular shift,
are blind, or are a teenager or older adult.
Delayed sleep phase disorder occurs when you go to bed and awaken two hours or more after
most people. You may think of yourself as a “night owl.” Teenagers and young adults are
more prone to this condition.

Advanced sleep phase disorder is the opposite of delayed sleep phase disorder. You actually
fall asleep a few hours before most people and then awaken very early in the morning.

Disorders related to your circadian rhythm may result in having difficulty falling asleep at
night, waking frequently throughout the night, and waking and not being able to go back to
sleep in the middle of the night.

Symptoms related to these conditions include:

• insomnia

• sleep loss

• problems waking in the morning

• tiredness throughout the day

• depression or stress

Other conditions that are tied into your circadian rhythm include:

• jet lag, caused from traveling over several time zones quickly

• shift work disorder, caused by an off-hours job or a job with unpredictable hours

• irregular sleep-wake disorder, caused by an inability to set a regular sleep and wake
schedule

Treating these conditions may include a variety of approaches. You may try to:

• set a more regular schedule

• use light therapy

• take medications or supplements like melatonin to fall asleep more easily

• try an intentional shift in your sleep implemented over several days or weeks
Health effects

Maintaining your circadian rhythm is vital to your health. If you experience a disruption to
your circadian rhythm and struggle to get the proper amount of sleep, you may experience
both short-term and long-term consequences to your health.

Disruption to your circadian rhythm can cause health conditions in several parts of the body
in the long term. This includes your:

• organs

• cardiovascular system

• metabolism

• gastrointestinal system

• skin

You may be more susceptible to diabetes, obesity, and mental health conditions as well.

Short-term disruptions to your circadian rhythm may result in problems with memory or lack
of energy. It may also take longer to heal an injury if you don’t get enough sleep.

When to talk with a doctor

There are several reasons you may want to talk to a doctor about an issue with your circadian
rhythm. If you experience one of these issues for a prolonged period, consider making a
doctor’s appointment:

• Have trouble achieving adequate sleep every night

• Cannot fall asleep easily

• Awaken several times a night and fail to get quality sleep

• Have trouble waking up

• Feel extremely tired during waking hours

The bottom line

Your circadian rhythm is your body’s natural way of keeping to its 24-hour body clock,
helping your body operate on a healthy sleep-wake schedule. Living a healthy, active lifestyle
that promotes proper rest will help you maintain this important component of your body.

Reach out to your doctor if you experience prolonged difficulties sleeping or extreme fatigue
during the day to find out how you can realign with your circadian rhythm and get proper
rest.

[Link]
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Endocrine neurons
Endocrine neurons are the effector cells of neurohemal organs. Their main secretory product
is a hormone that is released at the terminal membrane in response to
the depolarization caused by action potentials arriving from the perikaryon. In mammal
brains, endocrine neurons are largely restricted to the hypothalamus where they occur as two
distinct populations. One population includes the magnocellular neurons of the supraoptic
and paraventricular nuclei. Cells in both these nuclei elaborate and release the hormones
oxytocin or vasopressin. The other population comprises the parvicellular neurons that
synthesize and secrete the releasing hormones responsible for regulation of the
adenohypophysis. These are diffusely scattered through the hypothalamus but are most
densely concentrated in the region of the arcuate nucleus and in the periventricular zone. The
chapter reviews the similarities and differences between the release mechanisms of
cholinergic, adrenergic, and endocrine neurons. The cholinergic neuron does not have a
reuptake process, and recent evidence indicates that the endocrine neuron does not possess
this process either.
Neurotrasmitters
IMPORTANT NEUROTRANSMITTERS Some of the important neurotransmitters are
described KHUH 'HWDLOV RI
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141.1 and 141.2. „ ACETYLCHOLINE Acetylcholine is a cholinergic neurotransmitter. It
possesses excitatory function. It produces the excitatory function by opening the ligand-gated
sodium channels
Source Acetylcholine is the transmitter substance at the neuromuscular junction and synapse.
It is also released by the following nerve endings: 1. Preganglionic parasympathetic nerve 2.
Postganglionic parasympathetic nerve 3. Preganglionic sympathetic nerve 4. Postganglionic
sympathetic cholinergic nerves: i. Nerves supplying eccrine sweat glands ii. Sympathetic
vasodilator nerves in skeletal muscle 5. Nerves in amacrine cells of retina 6. Many regions of
brain.
Noradrenaline
Noradrenaline is the neurotransmitter in adrenergic
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Hypothalamus 4. Basal ganglia 5. Brainstem 6. Locus ceruleus in pons 7. Spinal cord. In
many places, noradrenaline is the excitatory chemical mediator and in very few places, it
causes inhi bition. It is believed to be involved in dreams, arousal and elevation of moods
„ DOPAMINE
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areas: 1. Basal ganglia 2. Hypothalamus 3. Limbic system 4. Neocortex 5. Retina
6PDOO LQWHQVHO\
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SRVVHVVHV inhibitory action. Prolactin inhibitory hormone
secreted by hypothalamus is considered to be dopamine
SEROTONIN Serotonin is otherwise known as 5-hydroxytryptamine (5-HT). It is
synthesized from tryptophan by hydroxylation and decarboxylation. Large amount of
serotonin (90%) is found in enterochromatin cells of GI tract. Small amount is found in
platelets and nervous system. It is secreted in the following structures: 1. Hypothalamus 2.
Limbic system 3. Cerebellum
'RUVDO UDSKH QXFOHXV
RI PLGEUDLQ 5. Spinal cord 6. Retina 7. GI tract 8. Lungs 9.
Platelets. It is an inhibitory substance. It inhibits impulses of pain sensation in posterior gray
horn of spinal cord. It is supposed to cause depression of mood and sleep
Serotonin causes vasoconstriction, platelet aggregation and smooth muscle vasoconstriction
Also control food intake
„ HISTAMINE Histamine is secreted in nerve endings of hypothalamus, limbic cortex and
other parts of cerebral cortex. It is also secreted by gastric mucosa and mast cells. Histamine
is an excitatory neurotransmitter. It is believed to play an important role in arousal
mechanism. „ GAMMA-AMINOBUTYRIC ACID Gamma-aminobutyric acid (GABA) is
an inhibitory neuro trans mitter in synapses particularly in CNS. It is responsible for
presynaptic inhibition. It is secreted by nerve endings in the following structures: 1. Cerebral
cortex 2. Cerebellum 3. Basal ganglia 4. Spinal cord 5. Retina. GABA causes synaptic
inhibition by opening potassium channels and chloride channels. So, potassium comes out of
synapse and chloride enters in (Chapter 140). This leads to hyperpolarization, which is
known as inhibitory postsynaptic potential (IPSP). „ SUBSTANCE P Substance P is a
neuropeptide that acts as a neurotransmitter and as a neuromodulator (see below). Substance
P is a polypeptide with 11 amino acid residues. It belongs to a family of 3 related peptides
called neurokinins or tachykinins. The other peptides of this family are neurokinin A and
neurokinin B which are not well known like substance P. Substance P is secreted by the nerve
endings
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peripheral nerves, different parts of brain particularly hypothalamus, retina and intestine
(Chapter 44). It mediates pain sensation. It is a potent vasodilator in CNS. It is responsible for
regulation of anxiety, stress, mood disorders, neurotoxicity, nausea and vomiting.
NITRIC OXIDE Nitric oxide (NO) is a neurotransmitter in the CNS. It is also the important
neurotransmitter in the neuroPXVFXODU MXQFWLRQV
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arterioles, NO activates the enzyme guanylyl cyclase, which in turn causes formation of
cyclic guanosine monophosphate (cGMP) from GMP. The cGMP is a smooth muscle
relaxant and it causes dilatation of arterioles. Thus, NO indirectly causes dilatation of
arterioles. Peculiarity of NO is that it is neither produced by the neuronal cells nor stored in
the vesicles. It is produced by non-neuronal cells like the endothelial cells of blood vessels.
From the site of production, it diffuses into the neuronal and non-neuronal cells where it
exerts its action.

Pituitary gland

he pituitary gland is one of eight interrelated major endocrine glands:

• Pineal gland.
• Pituitary gland.
• Thyroid gland.
• Thymus.
• Adrenal gland.
• Pancreas.
• Ovary (women only).
• Testis (men only).

The pituitary is often referred to as the “master gland” because it not only secretes its own
hormones, it tells other glands to produce hormones.

Your pituitary gland is divided into two main sections: the front (anterior) lobe and the back
(posterior) lobe. Connecting the hypothalamus and pituitary gland is a stalk of blood vessels
and nerves. Through that stalk, the hypothalamus communicates with the anterior lobe via
hormones and the posterior through nerve impulses.

The hypothalamus, which is above your pituitary gland, is the control center of some of your
body’s basic operations. It sends messages to your body’s autonomic nervous system, which
controls things like blood pressure, heart rate, respiration, body temperature, sleep-wake
cycle and digestion. The hypothalamus also tells the pituitary gland to produce and release
hormones.

hat does the pituitary gland do?

Glands are organs that secrete hormones — the “chemical messengers” of the body — that
travel through your bloodstream to different cells, telling them what to do. The major
hormones produced by the pituitary gland are:

• ACTH: Adrenocorticotrophic hormone. Stimulates the production of cortisol, a

“stress hormone” that maintains blood pressure and blood sugar levels.
• FSH: Follicle-stimulating hormone. Promotes sperm production and stimulates the
ovaries to produce estrogen.
• LH: Luteinizing hormone. Stimulates ovulation in women and testosterone production
in men.
• GH: Growth hormone. Helps maintain healthy muscles and bones and manage fat
distribution.
• PRL: Prolactin. Causes breast milk to be produced after childbirth. It also affects
hormones that control the ovaries and testes, which can affect menstrual periods,
sexual functions and fertility.
• TSH: Thyroid-stimulating hormone. Stimulates the thyroid gland, which regulates
metabolism, energy and the nervous system.
• Oxytocin: Helps labor to progress, causes breast milk to flow, affects labor,
breastfeeding, behavior and social interaction and the bonding between a mother and
child.
• ADH: Anti-diuretic hormone, or vasopressin. Regulates water balance and sodium
levels.

Hormones are not released from the pituitary gland in a steady stream. They come in bursts,
every one to three hours, and alternate between periods of activity and periods of inactivity.

Thyroid gland
Key Points
• Thyroid hormones are important in brain development by regulating cell migration
and differentiation, synaptogenesis, and myelination

• The early steps of embryonic neural development, such as neural induction,

neurulation, and establishment of polarity and segmentation, are probably not
influenced by thyroid hormones

• Deficient production of maternal thyroid hormones during the first half of gestation
may lead to neurological deficits and is a primary factor in the pathogenesis of
neurological cretinism

• Gene regulation by thyroid hormones in brain follows a strict temporal and regional
specificity; most genes are sensitive only during a limited time period of postnatal
 development, and some genes are under thyroid hormone control only in certain brain
regions

• Some of the morphological alterations induced by profound hypothyroidism might

actually be a consequence of the altered transcriptional activity of unliganded
receptors; receptor deletion is therefore not equivalent to hormone deprivation

• Unlike deletion of the thyroid hormone receptor, expression of dominant negative

receptors produces a phenotype more similar to the hypothyroid phenotype

• Thyroid hormones are important during development of the mammalian brain, acting
on migration and differentiation of neural cells, synaptogenesis, and myelination. The
actions of thyroid hormones are mediated through nuclear thyroid hormone receptors
(TRs) and regulation of gene expression. In developing humans maternal and fetal
thyroid glands provide thyroid hormones to the fetal brain, but the timing of receptor
ontogeny agrees with clinical data on the importance of the maternal thyroid gland
before midgestation. Several TR isoforms, which are encoded by
the THRA and THRB genes, are expressed in the brain, with the most common being
TRα1. Deletion of TRα1 in rodents is not, however, equivalent to hormone
deprivation and, paradoxically, even prevents the effects of hypothyroidism.
Unliganded receptor activity is, therefore, probably an important factor in causing the
harmful effects of hypothyroidism. Accordingly, expression of a mutant receptor with
impaired triiodothyronine (T3) binding and dominant negative activity affected
cerebellar development and motor performance. TRs are also involved in adult brain
function. TRα1 deletion, or expression of a dominant negative mutant receptor,
induces consistent behavioral changes in adult mice, leading to severe anxiety and
morphological changes in the hippocampus.

Neurons

There are three basic parts of a neuron: the dendrites, the cell body, and the axon. However,
all neurons vary somewhat in size, shape, and characteristics depending on the function and
role of the neuron.

Some neurons have few dendritic branches, while others are highly branched in order to
receive a great deal of information. Some neurons have short axons, while others can be quite
long.

Action potential
The dendrites of neurons receive information from sensory receptors or other neurons. This
information is then passed down to the cell body and on to the axon. Once the information
has arrived at the axon, it travels down the length of the axon in the form of an electrical
signal known as an action potential.
Synapse Communication

Once an electrical impulse has reached the end of an axon, the information must be
transmitted across the synaptic gap to the dendrites of the adjoining neuron. In some cases,
the electrical signal can almost instantaneously bridge the gap between the neurons and
continue along its path.

In other cases, neurotransmitters are needed to send the information from one neuron to the
next. Neurotransmitters are chemical messengers that are released from the axon terminals to
cross the synaptic gap and reach the receptor sites of other neurons. In a process known as
reuptake, these neurotransmitters attach to the receptor site and are reabsorbed by the neuron
to be reused.

Neuro trasmitters
Limbic system
Forms the limbus, or border, of the temporal lobes and is intimately connected to many otner
structures of the brain. Is concerned with subjective emotional experiences and changes in
bouny
functions associated with emotional states. It is particularly involved in aggressive,
submissive,
and sexual behavior and with pleasure, memory and learning, The limbic system is also assoc
ated with mood, motivation, and sensations.
Hippocampus: Contains large amounts of neurotransmitterS and consolidates recentiy ac
quired information about facts and events, turning short-term memory into long-term
memory.
Amygdala: Contains many opiate receptors and generates emotions from perceptions and
thoughts.
Cerebellum: Also called as "ittle brain", it is extensively involved with the processing of
sensory information and may be involved in cognitive, behavioral, and affective functions.
Ventricles: These are located in each cerebral hemisphere, center of the diencephalons and
in the region of the Pons and medulla oblongata. In certain psychiatric conditions, the
ventricles
are enlarged.
Spinal Fluid: Cerebro spinal fluid is produced from the blood choroids plexus located in
the ventricles, fills the ventricles, subarachnoid space and the spinal cord. This fluid bathes
the
brain with nutrients, cushions the brain within the skull, and exits through the blood stream.
Measuring neurotransmitters in the CSF, plasma, and urine, which gives an idea of
neurotrans-
mitter production, and metabolism in the brain identifies abnormal neurotransmission in some

mental disorders.
Blood-Brain and Blood-CSF Barriers: These proiect the central nervous system in several

ways. The brain and spinal cord are protected from neurotransmitters in the blood, such as
epi-
nephrine produced by the adrenal gland. Toxins are also excluded and hence many drugs are
not

able to enter the brain and spinal cord. Similarly, neurotransmitters produced in the CNS are
prevented from leaking into the general circulation.
Many of the psychiatric disorders are thought to be caused by an over-response or an under-
response somewhere along the complex process of neurotransmission. Psychosis is thought to

involve excessive dopamine neurotransmission. Depression and Mania are thought to result
from

disruption of normal patterns of neurotransmission of nor- epinephrine, serotonin and other

neu-
rotransmitters. Anxiety is thought to be due to a dysregulation of gamma-amino butyric acid

GABA) and endogenous anti-anxiety chemicals.

The drugs affect the process of neurotransmission at the synapse in several ways:
Release: More neurotransmitter is released into the synapse from the storage vesicles in the
pre-synaptic cell.
i.

Blockade: The neurotransmitters are prevented from binding to the post-synaptic receptor.
i.

ii. eCeptor Sensitivity Changes: The receptor becomes more or less responsive to the neu-
rotransmitter.
Abnormal neuro trasmiter
Like a key inserted into a lock, each of these chemicals fits precisely into specific receptor
cells (made of protein) embedded in the membranes of the axons and dendrites. These
receptor
cells then either open or close doors (ion channels) into the cell, allowing for the interchange
of

chemicals. This triggers a cascade of chemical and electrical processes that are caused by a
vari-
ety of chemicals within the cell itself. These chemicals regulate the function of the ion
channels,

the production of neurotransmitters and their release into the synapse, and continue the
process of
neurotransmission.

Depending on the type of the neurotransmitter, the receiving cells are either stimulated (pro-
ducing an action) or inhibited (stopping an action). After release into the synapse and
communi-
cation with receptor cells, the neurotransmitters are transported back from the synapse into
the

axon in a process called reuptake, where they are stored for future use or are inactivated (me-
1abolized) by enzymes.