The Neuroscience Center

Neurons

• transmit information to other nerve cells, muscle, or gland cells

• brain is what it is because of the structural and functional properties of interconnected neurons

• 100 million and 100 billion neurons, depending on the species

 

There are 3 types of neurons in the nervous system:

 

1. sensory

• detect and respond to different attributes of the internal and external environment

• coupled to receptors

• light, sound, mechanical and chemical stimuli subserve the sensory modalities of vision, hearing, touch, smell and taste

 

2. motor

• control the activity of muscles

• responsible for all forms of behaviour including speech

 

3. interneurons

• mediate simple reflexes as well as being responsible for the highest functions of the brain

• these are by far the most numerous in the human brain

 

Large size in relation to body size: enormous increase in the number of interneurons over the course of evolution

These basic structures of the nervous system are the same in all vertebrates.

 

mammalian neuron consists of a cell body, dendrites, and an axon

 

Cell Body contains the nucleus and cytoplasm

 

Axon extends from the cell body and often gives rise to many smaller branches before ending at nerve terminal

range in length from a tiny fraction of a centimeter to about one meter+

 

Dendrites extend from the neuron cell body and receive messages from other neurons

 

Synapses are the contact points where one neuron communicates with another. The dendrites are covered with synapses formed by the ends of axons from other neurons

 

Communication= electrical impulses along their axons

 

Many axons are covered with a layered myelin sheath, which accelerates the transmission of electrical signals along the axon. This sheath is made by specialized cells called glia

 

The outer membranes of neurons, made of fatty substances, are draped around a cytoskeleton that is built up of rods of tubular and filamentous proteins that extend out into dendrites and axons alike.

 

CNS: Glia that make the sheath are called oligodendrocytes

PNS: Glia known as Schwann cells

 

Brain contains  Glia:Neurons 10:1

 

Glia

1. glia transport nutrients to neurons

2. clean up brain debris

3. digest parts of dead neurons

4. help hold neurons in place

 

Glial cells, long thought to have a purely supporting function to the neurons, are now known to make an important contribution to the development of the nervous system and to its function in the adult brain. They do not transmit information in the way that neurons do.

 

Nerve impulses

 

• Nerve impulses involve the opening and closing of ion channels

• selectively permeable

• water-filled molecular tunnels that pass through the cell membrane

• allow ions to enter or leave the cell

 

flow of ions creates an electrical current that produces tiny voltage changes across the neuron’s cell membrane.

ability of a neuron to generate an electrical impulse depends on a difference in charge between the inside and outside of the cell

neuron switches from an internal negative charge to a positive charge state.

The change, called an action potential, then passes along the axon’s membrane at speeds up to several hundred miles per hour

In this way, a neuron may be able to fire impulses multiple times every second.

 

Voltage changes reach the end of an axon, they trigger the release of neurotransmitters, the brain’s chemical messengers.

 

These are usually currents that come into the cell, called excitation, or they may be currents that move out of the cell, called inhibition.

 

Neurotransmitters

 

released at nerve terminals

diffuse across the synapse

bind to receptors on the surface of the target cell (often another neuron, also possibly a muscle or gland cell)

receptors act as on and-off switches for the next cell

fits into this region in much the same way that a key fits into a lock

interaction alters the target cell’s membrane potential and triggers a response from the target cell, such as the generation of an action potential, the contraction of a muscle, the stimulation of enzyme activity, or the inhibition of neurotransmitter release

Classified biochemically

 

Acetylcholine

 

first neurotransmitter to be identified

released by neurons connected to voluntary muscles, causing them to contract, and by neurons that control the heartbeat

transmitter in many regions of the brain

synthesized in axon terminals

action potential arrives at the nerve terminal, electrically charged calcium ions rush in, and ACh is released into the synapse, where it attaches to ACh receptors on the target cells

On voluntary muscles, this action opens sodium channels and causes muscles to contract

ACh is then broken down by the enzyme acetylcholinesterase and resynthesized in the nerve terminal

 

Much less is known about ACh in the brain

may be critical for normal attention, memory, and sleep.

 

Drugs that inhibit acetylcholinesterase are presently the main drugs used to treat Alzheimer’s disease

Where in the body is it mostly present?

 

Amino Acids (AGGG)

 

• Aspartate

• Glutamate

• GABA

• Glycine

 

widely distributed throughout the body and the brain

Certain amino acids can also serve as neurotransmitters in the brain

 

• GABA

• Glycine

 

glycine and GABA inhibit the firing of neurons

activity of GABA is increased by benzodiazepines (e.g., valium) and by anticonvulsant drugs

 

• Aspartate

• Glutamate

 

Glutamate and aspartate act as excitatory signals, activating, among others, NMDAR which, in developing animals, have been implicated in activities ranging from learning and memory to development and specification of nerve contacts.

stimulation of NMDA receptors may promote beneficial changes in the brain, overstimulation can cause nerve cell damage or cell death.

 

 

Biogenic Amines

 

Catecholamines

 

• Dopamine

• Norepinephrine

• Epinephrine 

• Histamine

• Serotonin

 

Dopamine and Norepinephrine are widely present in the brain and peripheral nervous system

 

Dopamine

 

present in three principal circuits in the brain

circuit that regulates movement has been directly linked to disease

 

Due to dopamine deficits in the brain, people with Parkinson’s disease show such symptoms as muscle tremors, rigidity, and difficulty in moving

 

Administration of levodopa, a substance from which dopamine is synthesized, is an effective treatment for Parkinson’s, allowing patients to walk and perform skilled movements more successfully

 

Another dopamine circuit is thought to be important for cognition and emotion

abnormalities in this system have been implicated in schizophrenia

Because drugs that block certain dopamine receptors in the brain are helpful in diminishing psychotic symptoms, learning more about dopamine is important to understanding mental illness.

 

In a third circuit, dopamine regulates the endocrine system.

Dopamine directs the hypothalamus to manufacture hormones and hold them in the pituitary gland for release into the bloodstream or to trigger the release of hormones held within cells in the pituitary.

 

Norepinephrine

 

Deficiencies occur in patients with Alzheimer’s disease, Parkinson’s disease, and Korsakoff’s syndrome, a cognitive disorder associated with chronic alcoholism. These conditions all lead to memory loss and a decline in cognitive functioning.

Thus, researchers believe that norepinephrine may play a role in both learning and memory.

Norepinephrine is also secreted by the sympathetic nervous system throughout the body to regulate heart rate and blood pressure.

Acute stress increases release of norepinephrine from sympathetic nerves and the adrenal medulla, the innermost part of the adrenal gland.

 

Serotonin

 

present in the brain and other tissues, particularly blood platelets and the GI tract lining

brain, serotonin has been identified as an important factor in sleep quality, mood, depression, and anxiety

BC serotonin controls different switches affecting various emotional states, scientists believe these switches can be manipulated by analogs, chemicals with molecular structures similar to that of serotonin

Drugs that alter serotonin’s action, such as fluoxetine, relieve symptoms of depression and obsessive-compulsive disorder

 

NeuroPeptides

 

Can be subdivided:

1. Tachykinins

2. Neuropophyseal hormones

3. Hypothlamic-releasing hormones

4. Opioid Peptides

5. The "Others"

 

Vary in lengths, from 3 to 30+ amino acid residues

synthesized in the cell body and greatly outnumber the classical transmitters discussed earlier

1973, scientists discovered receptors for opiates on neurons in several regions of the brain, suggesting that the brain must make substances very similar to opium.

Shortly thereafter, scientists made their 1st discovered opiate peptide produced by brain:

enkephalin (resembles morphine), literally meaning “in the head.”

Soon after, other types of opioid peptides were discovered. These were named endorphins, meaning “endogenous morphine.”

precise role of the naturally occurring opioid peptides is unclear

Simple hypothesis: released by brain neurons in times of stress to minimize pain and enhance adaptive behavior

Some sensory nerves — tiny unmyelinated C fibers — contain a peptide called substance P, which causes the sensation of burning pain.

The active component of chili peppers, capsaicin, causes the release of substance P, something people should be aware of before eating them.

 

Trophic Factors

 

small proteins in the brain that are necessary for the development, function, and survival of specific groups of neurons.

made in brain cells, released locally in the brain, and bind to receptors expressed by specific neurons.

identified genes that code for receptors and are involved in the signaling mechanisms of trophic factors

This information should also prove useful for the design of new therapies for brain disorders of development and for degenerative diseases, including Alzheimer’s disease and Parkinson’s disease

 

Hormones

 

NS uses NTs as its chemical signals, endocrine system uses hormones as its chemical signals

 

1. pancreas

2. kidneys

3. heart

4. adrenal glands

5. gonads

6. thyroid

7. parathyroid

8. thymus

9. fat

 

are all sources of hormones.

 

endocrine system works in large part by acting on neurons in the brain, which controls the pituitary gland.

pituitary gland secretes factors into the blood that act on the endocrine glands to either increase or decrease hormone production (feedback loop A-B-A)

 

E-Pg FLoop is very important for the activation and control of basic behavioral activities, such as :

 

1. sex

2. emotion

3. responses to stress 

4. eating

5. drinking

6. regulation of body functions

7. including growth

8. reproduction

9. energy use

10. metabolism

 

brains response to hormones indicates that the brain is very malleable and capable of responding to environmental signals

 

brain contains receptors for thyroid hormones and the six classes of steroid hormones, which are synthesized from cholesterol:

 

1. androgens

2. estrogens

3. progestins

4. glucocorticoids (adrenal cortex)

5. mineralocorticoids (adrenal cortex)

6. vitamin D

 

Thyroid and steroid hormones bind to receptor proteins that in turn bind to DNA and regulate the action of genes. This can result in long-lasting changes in cellular structure and function

brain has receptors for many hormones; for example, the metabolic hormones insulin, insulin-like growth factor, ghrelin, and leptin. These hormones are taken up from the blood and act to affect neuronal activity and certain aspects of neuronal structure

In response to stress and changes in our biological clocks, such as day and night cycles and jet lag, hormones enter the blood and travel to the brain and other organs.hormones alter the production of gene products that participate in synaptic neurotransmission as well as affect the structure of brain cells. As a result, the circuitry of the brain and its capacity for neurotransmission are changed over a course of hours to days. In this way, the brain adjusts its performance and control of behavior in response to a changing environment.

Hormones are important agents of protection and adaptation, but stress and stress hormones, such as the glucocorticoid cortisol, can also alter brain function, including the brain’s capacity to learn. Effects brains ability to learn, but the brain can also secure a remarkable recovery

 

Reproduction in females is a good example of a regular, cyclic process driven by circulating hormones and involving a feedback loop:

 

1. Neurons in the hypothalamus produce (GnRH), (G acts on pituitary)

 

2. Both males and females, this causes two hormones —FSH and LH— to be released into the bloodstream.

 

3. A. Females, these hormones act on the ovary to stimulate ovulation and promote release of the ovarian hormones estradiol and progesterone.

 

3. B. In males, these hormones are carried to receptors on cells in the testes, where they promote spermatogenesis and release the male hormone testosterone, an androgen, into the bloodstream.

 

4. increased levels of testosterone in males and estrogen in females act on the hypothalamus and pituitary to decrease the release of FSH and LH

 

5. increased levels of sex hormones induce changes in cell structure and chemistry, leading to an increased capacity to engage in sexual behavior.

 

6. Sex hormones also exert widespread effects on many other functions of the brain, such as attention, motor control, pain, mood, and memory.

 

Sexual differentiation of the brain is caused by sex hormones acting in fetal and early postnatal life, although recent evidence suggests genes on either the X or Y chromosome may also contribute to this process.

 

Gender Differences in Cognition

 

statistically & biologically sign differences between the brains of men and women that are similar to sex differences found in experimental animals

 

differences in:

• size and shape of brain structures in the hypothalamus

• arrangement of neurons in the cortex and hippocampus

• well beyond sexual behavior and reproduction

• affect many brain regions and functions

• perceiving pain

• dealing with stress

• strategies for solving cognitive problems

• brains of men and women are more similar than they are different

 

Anatomical differences have also been reported between the brains of heterosexual and homosexual men.

hormones and genes act early in life to shape the brain in terms of sex-related differences in structure and function.

 

Gases and Other unusual Neurotransmitters

 

new class of neurotransmitters that are gases

molecules — nitric oxide and carbon monoxide — do not act like other neurotransmitters

not stored in any structure, certainly not in storage structures for classical and peptide transmitters

made by enzymes as they are needed and released from neurons by diffusion

Rather than acting at receptor sites, these gases simply diffuse into adjacent neurons and act upon chemical targets, which may be enzymes.

 

CO2=??, but NO has already been shown to play several important roles:

governs erection in the penis.

nerves of the intestine, it governs the relaxation that contributes to the normal movements of digestion. In the brain, nitric oxide is the major regulator of the intracellular messenger molecule cyclic GMP. In conditions of excess glutamate release, as occurs in stroke, neuronal damage following the stroke may be attributable in part to nitric oxide.

 

 

Lipid Messengers

 

1. Prostaglandins are a class of compounds made from lipids by an enzyme called cyclooxygenase.

very small and short-lived molecules have powerful effects

fever and the generation of pain in response to inflammation. Aspirin reduces a fever and lowers pain by inhibiting the cyclooxygenase enzyme

 

2. membrane-derived messenger is the brain’s own marijuana, endocannabinoids

messengers control the release of neurotransmitters, usually by inhibiting them, and can also affect the immune system and other cellular parameters still being discovered

play an important role in the control of behaviors. They increase in the brain under stressful conditions

 

Second Messengers

 

Substance that triggers cascade of events in post-synaptic cells

Convey the msg of the NT

may endure for a few milliseconds to as long as many minutes

may be responsible for long-term changes in the nervous system

example of the initial step in the activation of a second messenger system involves ATP

ATP is present throughout the cytoplasm of all cells.

For example, when norepinephrine binds to its receptors on the surface of the neuron, the activated receptor binds a G protein on the inside of the membrane.

The activated G protein causes the enzyme adenylyl cyclase to convert ATP to cAMP, the second messenger.

Rather than acting as a messenger between one neuron and another, cAMP exerts a variety of influences within the cell, ranging from changes in the function of ion channels in the membrane to changes in the expression of genes in the nucleus.

Play a role in the manufacture and release of neurotransmitters and in intracellular movements and carbohydrate metabolism in the cerebrum

 

Involved in growth and development processes.

Direct effects of second messengers on the genetic material of cells may lead to long-term alterations in cellular functioning and, ultimately, to changes in behavior.