ELEMENTARY BRAIN
Electricity and Chemicals
In order to maintain the cell membrane potential, cells keep a low intracell concentration of sodium ions and high extracell levels of potassium ions.
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First NT discovered
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Axon terminals
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attention, memory, sleep
Antibodies that block one type of ACh receptor cause myasthenia gravis, a disease characterized by fatigue and muscle weakness
Because ACh-releasing neurons die in Alzheimer’s patients, finding ways to restore this neurotransmitter is a goal of current research
Huntington’s disease, a hereditary disorder that begins in 40's, the GABA-producing neurons in brain centers that coordinate movement degenerate, causing uncontrollable movements.
Nerve cell death is what happens as a result of trauma and during a stroke.
NMDAR drugs holds promise for improving brain function and treating neurological and psychiatric disorders.
Nigrostriatal deficit causes parkinsons
Mesocorticolimbic deficit causes schizophrenia
Tuberinfundibular deficit causes hyper/hypo-prolactinamia
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L-dopa restores some movement
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5 receptors
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Deficit causes Alzh's, park's, korsk's
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Mem loss and decline cog functioning
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learning
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memory
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SNS skeletal Shit!!!
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Brain, Blood platelets, Gi Tract Lining
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sleep quality, mood, depression, and anxiety
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Can be imitated by Analogs
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Fluoxetine relieve depression and OCD
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3-30+
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cell-synthesized
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Wow, we found Receptors, then
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enkephalin first discovered opiate
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then came endorphins
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minimize stress and enhance adaptive behavior
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subsP- you feel me?
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capsaicin is capping all your pain subs
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proteins
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development, funciton, survival, of neurons
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synthesized locally
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NS to chem like ES to hormones
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9 sources of hormones
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endocrine acts on pits of t(h)erry
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Feedback loop signalling
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controls 10+ basic human behaviors
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responsive to environment (ex. time zones)
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6 cholesterol-synthesized steroid hormones
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regulate DNA
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long-term changes
brain can recieve:
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insulin
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ghrelin
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leptin
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insulin-like growth factor
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protection and adaptation, also can affect memory from chronic stress
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due to gluco-corticoid cortisol
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in spite of, brain can recover
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Female reproductive cycle-feedback loop
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6-step
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some similarities with males
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GnRH
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FSH
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LH
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estradiol
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progesterone
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testosterone
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size
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shape
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arrangement
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pain
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stress
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test probs
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hormones
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genes
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Made by enzymes
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NO and CO2 dissolve to act on chem targets (ex. Enzymes)
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NO, lets be erect!
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governs muscle relaxation (GI)
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excess gluta + NO = damage
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small, short lived, powerful effects
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Prostalipid will cyclo your oxygenase
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fever, inflame, pain
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Aspirin aspires to stop cyc-ling
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Endocannabinoids inhibit NT rel.
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immune system and control behaviors
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increase when stressed
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legacy of an NT
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milliseconds to +minutes
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long-term
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ATP- involved
Neurons and the Action Potential
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Nerve impulses involve the opening and closing of ion channels
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selectively permeable (TO K)
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water-filled molecular tunnels that pass through the cell membrane
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allow ions to enter or leave the cell
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Nitric oxide is a neurotransmitter not released by exocytosis
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.
The end-points of the axons also respond to molecules called growth factors. These enable the neuron to grow longer dendrites or make yet other dynamic changes to its shape or function.
When the dendrite receives one of the chemical messengers that has been fired across the synapse, miniature electrical currents are set up inside the receiving dendritic spine.
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A pulse of sodium ions flashes into the cell and a new equilibrium of +30 mV is established within a millisecond.
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Opens K+ channels, triggering a pulse of potassium ions to flow out of the cell, almost as rapidly as the Na+ ions that flowed inwards
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In turn causes the membrane potential to swing back again to its original negative value on the inside.
Remarkably few ions traverse the cell membrane to do this, and the concentrations of Na+ and K+ ions within the cytoplasm do not change significantly during an AP.
In myelinated neurons, action-potentials can race along at 120 m/s!
The most efficient axons can conduct action potentials at frequencies up to 1000 times per second.
ATP Pump
In order to maintain the cell membrane potential, cells keep a low intracell NA ions and high intracell K ions.
The sodium-potassium pump moves 3 sodium ions out and moves 2 potassium ions in, thus, in total, removing one positive charge carrier from the intracellular space.
The action of the sodium-potassium pump is not the only mechanism responsible for the generation of the resting membrane potential.
Also, the selective permeability of the cell's plasma membrane for the different ions plays an important role.
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The pump, after binding ATP, binds 3 intracellular Na+ ions.
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ATP is hydrolyzed, leading to phosphorylation of the pump at a highly conserved aspartate residue and subsequent release of ADP.
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A conformational change in the pump exposes the Na+ ions to the outside.
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The phosphorylated form of the pump has a low affinity for Na+ ions, so they are released.
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The pump binds 2 extracellular K+ ions.
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This causes the dephosphorylation of the pump, reverting it to its previous conformational state, transporting the K+ ions into the cell.
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The unphosphorylated form of the pump has a higher affinity for Na+ ions than K+ ions, so the two bound K+ ions are released.
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ATP binds, and the process starts again.
more information: https://en.wikipedia.org/wiki/Resting_potential#Generation_of_the_resting_potential
Chemical Messengers
The arrival of an action potential leads to the opening of ion-channels that let in calcium.
Enzymes:
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Snare
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Tagmin
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Brevin
act on a range of presynaptic proteins.
Causes exocytosis into the 20 nanometre gap called the synaptic cleft.
Fates of an NT:
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transporters (glia) suck up the transmitter in the cleft (process NT & send back to storage vesicles of nerve endings for future use)
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nerve cells pump the transmitter molecules back directly into their nerve endings
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NT is broken down by other chemicals in the synaptic cleft
If the ion channel allows positive ions (Na+ or Ca2+) to enter, the inflow of positive current leads to excitation.
Two inhibitory neurotransmitters
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GABA
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glycine
Excitatory neurotransmitter
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glutamate
Neuromodulators
Neuromodulators: relatively few in number but their axons project widely through the brain
Action of metabotropic receptors is called neuromodulation.
The effects of neuromodulation include changes in:
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ion channels
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receptors
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transporters
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the expression of genes
These changes are slower in onset and more long-lasting than those triggered by the excitatory and inhibitory transmitters and their effects extend well beyond the synapse.
Although they don`t initiate action potentials, they have profound effects on the impulse traffic through neural networks.
Among the many messengers acting on G-protein coupled receptors are:
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acetylcholine
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dopamine
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noradrenaline
Noradrenaline
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Released in response to various forms of novelty and stress
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helps to organise the complex response of the individual to new/stressful challenges
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Noradrenaline cells are located in the locus coeruleus (LC)
1600 noradrenaline neurons in the human brain, but they send axons to all parts of the brain and spinal cord. These neuromodulatory transmitters do not send out precise sensory information, but fine-tune dispersed neuronal assemblies to optimise their performance.
Dopamine
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Makes certain situations rewarding for the animal, by acting on brain centres associated with positive emotional features.
Acetylcholine
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Acts on both ionotropic and metabotropic receptors.
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The first neurotransmitter to be discovered.
Ionic mechanisms to signal across the neuromuscular junction from motor neurons to striated muscle fibres.
It can also function as a neuromodulator. It does this, for example, when you want to focus attention on something - fine-tuning neurons in the brain to the task of taking in only relevant information.
Neurotransmitters
released at nerve terminals
diffuse across the synapse
bind to receptors on the surface of the target cell (neuron, muscle, 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
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synthesized in axon terminals
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action potential arrives at the nerve terminal
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electrically charged calcium ions rush in
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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)
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Aspartate
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Glutamate
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GABA
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Glycine
widely distributed throughout the body and the brain
Certain amino acids can also serve as neurotransmitters in the brain
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GABA
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Glycine
glycine and GABA inhibit the firing of neurons
activity of GABA is increased by benzodiazepines (e.g., valium) and by anticonvulsant drugs
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Aspartate
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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
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Dopamine
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Norepinephrine
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Epinephrine
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Histamine
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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
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:
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Tachykinins
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Neuropophyseal hormones
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Hypothlamic-releasing hormones
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Opioid Peptides
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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
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pancreas
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kidneys
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heart
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adrenal glands
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gonads
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thyroid
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parathyroid
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thymus
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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 :
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sex
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emotion
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responses to stress
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eating
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drinking
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regulation of body functions
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including growth
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reproduction
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energy use
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metabolism
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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:
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androgens
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estrogens
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progestins
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glucocorticoids (adrenal cortex)
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mineralocorticoids (adrenal cortex)
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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:
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metabolic hormones insulin
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insulin-like growth factor
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ghrelin
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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 NTmission 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.
Affects 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:
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size and shape of brain structures in the hypothalamus
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arrangement of neurons in the cortex and hippocampus
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well beyond sexual behavior and reproduction
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affect many brain regions and functions
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perceiving pain
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dealing with stress
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strategies for solving cognitive problems
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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 incredibly 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 to lower pain and enhance adaptive behavior.
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.
Intricate communication systems in the brain and the nervous system begin to develop about three weeks after gestation
Testosterone, estrogen, and progesterone are often referred to as sex hormones.


1. Embryonic induction
Cell Division & Cell Differentiation
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individual cells stop dividing
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take on specific characteristics ex. neurons or glial cells
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Differentiation orders things spatially
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Different neurons various locations (pf)
three layers emerge
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endoderm
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ectoderm
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mesoderm
each cell contains 25,000 genes containing the entire sequence of DNA instructions for development
signaling molecules released by the mesoderm turn on certain genes and turn off others, triggering some ectoderm cells to become nerve tissue in a process called neural induction
Subsequent signaling interactions further refine the nerve tissue into the basic categories of neurons or glia (support cells), then into subclasses of each cell type. The remaining cells of the ectoderm, which have not received the signaling molecules diffusing from the mesoderm, become skin.
proximity of cells to the signaling molecules largely determines their fate; concentration of these molecules spreads out and weakens the farther it moves from its source
Embryonic Induction: The influence of one cell group (inducer) over a neighboring cell group (induced) during embryogenesis. Also known as induction.
Sonic Hedgehog, is secreted from mesodermal tissue lying beneath the developing spinal cord. (position-sensing mechanism for neurons).
The bottom part of the neural tube expresses SHH
diffuses away from FPlate
affects cells on the dorsoventral axis according to their distance from the floor plate.
SHH concentration induces the expression of a gene:
Closest: specialized class of glia (g-g, n-g)
Farther: lower concentrations become motor neurons (n-m)
Even farther: interneurons (n-n)
2. Migration AKA Pattern Formation
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journey to the proper position in the brain
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begins 3-4 weeks after conception
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third week when the embryo = 2 connected sheets of dividing cells
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ectoderm starts to thicken and build up along the middle
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cells continue to divide
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a flat neural plate grows
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followed by the formation of parallel ridges
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similar to the creases in a paper airplane that rise across its surface
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Days later, the ridges fold in toward each other and fuse to form a hollow neural tube
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top of the tube thickens into three bulges that form the hindbrain, the midbrain, and the forebrain
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week 7: first signs of eyes and the brain’s hemispheres appear
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As neurons are produced, they move from the neural tube’s ventricular zone, or inner surface, to near the border of the marginal zone, or outer surface
After neurons stop dividing, they form an intermediate zone, where they gradually accumulate as the brain develops.
then migrate to their final destination— with the help of a variety of guidance mechanisms.
The most common guidance mechanism, accounting for about 90 percent of migration in humans, are:
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glia- project radially from the intermediate zone to the cortex. provide a temporary scaffolding for ushering neurons to their destination.
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inhibitory interneurons, small neurons with short pathways usually found in the central nervous system, migrate tangentially across the brain
Additional helpers for migration
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principal axes of the nervous system
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embryo sets up a number of localised polarizing regions in the neural tube that secrete signal molecules. form a gradient of concentration with distance.
This process can be affected by different factors
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External forces, such as alcohol, cocaine, or radiation, can prevent proper migration, resulting in misplacement of cells, which may lead to mental retardation or epilepsy
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Mutations in genes that regulate migration have been shown to cause some rare genetic forms of retardation and epilepsy in humans
3. Specializing
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reach their final location
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must make the proper connections so ex. vision/hearing can emerge
Various regions of the early nervous system express different subsets of genes, presaging the emergence of brain areas - forebrain, midbrain and hindbrain - with distinct cellular architecture and function.
Induction, proliferation, and migration -->>> occur internally during fetal development
Next phases of brain development -->>>dependent on interactions with the environment
After birth and beyond, such activities as listening to a voice, responding to a toy, and even the reaction evoked by the temperature in the room lead to more connections among neurons
Neurons become interconnected through growth of:
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dendrites; extensions of the cell body that receive signals from other neurons
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axons; extensions from the neuron that can carry signals to other neurons.
Axons enable connections between neurons at considerable distances, sometimes at the opposite side of the brain, to develop. In the case of motor neurons, the axon may travel from the spinal cord all the way down to a foot muscle.
GC, specialized for moving through tissue
target reached=no longer able to voyage
Target cell selected with high precision
may have to cross over other growth cones heading for different places.
Along the path, guidance cues that attract (+) or repel (-) the growth cones help them find their way
Many molecules help guide growth cones, some molecules either:
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lie on the cells that growth cones contact
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are released from sources found near the growth cone; bear molecules that serve as receptors for the environmental cues
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binding of particular signals with receptors tells the growth cone whether to move forward, stop, recoil, or change direction. (proteins with names such as netrin, semaphorin, and ephrin)(families of molecules are used; at least fifteen semaphorins and at least nine ephrins)
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axons reach their targets
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form connections with other cells at synapses
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the electrical signal of the sending axon is transmitted by chemical neurotransmitters to pt-syn
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either provoke or prevent the generation of a new signal
Responsible for the astounding information-processing capacity of the brain:
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regulation of transmission at synapses
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integration of inputs from the thousands of synapses each neuron receives
Connectional specificity: For processing to occur properly, the connections must be highly specific.
Specific sites on the neuron are dedicated to recieving and sending an action potential
Specificity arises from the mechanisms that guide each axon to its proper target area
Additional molecules mediate target recognition when the axon chooses the proper neuron.
They often also mediate the proper part of the target once the axon arrives at its destination.
Dendrites also are actively involved in the process of initiating contact with axons and recruiting proteins to the “postsynaptic” side of the synapse
The tiny portion of the axon that contacts the dendrite becomes specialized for the release of neurotransmitters, and the tiny portion of the dendrite that receives the contact becomes specialized to receive and respond to the signal.
also other ensure that the synapse can transmit signals quickly and effectively.
and other molecules coordinate the maturation of the synapse after it has formed so that it can accommodate the changes that occur as our bodies mature and our behavior changes.
A combination of signals also determines the type of neurotransmitters that a neuron will use to communicate with other cells. For some cells, such as motor neurons, the type of neurotransmitter is fixed, but for other neurons, it is not.
Just as genes turn on and off signals to regulate the development of specialized cells, a similar process leads to the production of specific neurotransmitters
Location of the synapse determines what gene will express and the chem msngers produced
Despite spatial arrangement & specific connectivity is established, wiring is subject to activity-dependent refinement, ex. pruning of axons and the death of neurons.
Critical Periods
CP: the developing nervous system must obtain certain critical experiences, such as sensory, movement, or emotional input, to mature properly.
characterized by:
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high learning rates
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enduring consequences for neuronal connectivity
After a critical period, connections diminish in number and are less subject to change, but the ones that remain are stronger, more reliable, and more precise. turn into the unique variety of sensory, motor, or cognitive “maps” that best reflect our world
The last step in the creation of an adult human brain, the frontal lobes, whose function includes judgment, insight, and impulse control, continues into the early 20s
Ex.1. a monkey raised from birth to 6 months of age with one eyelid closed permanently lost useful vision in that eye because of diminished use. Loss of vision is caused by the actual loss of functional connections between that eye and neurons in the visual cortex. This finding has led to earlier and better treatment for the eye disorders of congenital cataracts and “lazy eye” in children. Sharp vision influenced by patterned electrical activity in the retina & initial exuberant set of connections is sculpted during a critical period, after which the basic pattern of the visual system is complete, at around eight weeks of age in monkeys, perhaps a year in humans.
Ex.2. cochlear implants introduced in infancy are most effective in restoring hearing to the congenitally deaf.
Cognitive recovery greatest early in life:
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social deprivation
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brain damage
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stroke
Many people have observed that children can learn languages or develop musical ability (absolute pitch) with greater proficiency than adults.
Heightened activity in the critical period may, however, also contribute to an increased incidence of certain disorders in childhood, such as epilepsy. Fortunately, as brain activity subsides, many types of epilepsy fade away by adulthood.

Advances in the study of medical treatments.
once thought some were purely disorders of adult function,
such as schizophrenia, are now being considered in
developmental terms; that is, such disorders may occur
because pathways and connections to the brain did
not form correctly early in life
Radial migration: the cells that arrive the earliest (the oldest ones) form the deepest layer of the cortex whereas the late-arriving (the youngest) neurons form the outermost layer.
Many of our genes are shared with the fruit fly, Drosophila.
Indeed, thanks to studies of the fruit fly, the majority of the genes known to be important in human nervous system development were first identified.

Most of these proteins are common to many organisms—worms, insects, and mammals, including humans. Each protein family is smaller in flies or worms than in mice or people, but its functions are quite similar. As a result, it has been possible to use the simpler animals as experimental models to gain knowledge that can be applied directly to humans.
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First netrins guide neurons around the worm’s “nerve ring.”
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vertebrate netrins were found to guide axons around the mammalian spinal cord.
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Receptors for netrins were then found in worms, a discovery that proved to be invaluable in finding the corresponding, and related, human receptors.
Defects in molecules who coordinate maturation are now thought to make people susceptible to disorders such as autism
loss of other molecules may underlie the degradation of synapses that occurs during aging
most neuronal cell death occurs in the embryo
paring down of connections occurs in large part during critical periods in early postnatal lif
Heightened activity in the critical period may, however, also contribute to an increased incidence of certain disorders in childhood, such as epilepsy. Fortunately, as brain activity subsides, many types of epilepsy fade away by adulthood.


DRUGS AND THE BRAIN
Drugs differ in their dependence liability
high risk: cocaine, heroin and nicotine
lower risk: alcohol, cannabis, ecstasy and amphetamines
Drugs by dependancy rates:
Nicotine, heroin, cocaine, alcohol, marijuana and tranquilizers and prescription meds
Drugs by popularity:
Alcohol, Nicotine, marijuana, cocaine, heroin, tranquilizers and prescription meds
primary sites of action are all different, these drugs share an ability to promote release of dopamine in certain brain regions.
not necessarily akin to triggering a “pleasure” mechanism, it is thought that the drug-induced release of dopamine may be an important final common pathway of “pleasure” in the brain. It represents the signal that prompts a person to carry on taking the drug.
Alcohol
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dampen excitatory messages and promote inhibition
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~1/10 regular drinkers will become dependent alcoholics
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Lt damages the body, especially the liver, and can cause permanent damage to the brain
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Pregnant + alc = damaged brains and low IQ’s
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>30,000 people die every year in Britain from alcohol-related diseases
Nicotine
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acetylcholine; activate natural alerting mechanisms in the brain
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concentrate and soothing effect
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highly addictive and many smoke to avoid the unpleasant signs of withdrawal
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no effect on the brain, tobacco smoke damaging to lungs and lt exposure can lead to lung cancer and also to other lung and heart diseases
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>100,000 people die every year in Britain from smoking related diseases
Cannabis
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endocannabinoids
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control of muscles
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regulating pain sensitivity
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pleasurable and relaxing, dream-like state; perception of sounds, colours and time is subtly altered
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no one died from an overdose, may experience unpleasant panic attacks after large doses
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has been used at least once by nearly 1/2 the population of Britain <30
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smoke contains much the same mixture of poisons as cigerettes
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smokers tend to develop lung diseases and they run the risk of developing lung cancer
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~1/10 become dependent, which people who sell the drug are well aware of
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incompatible with the skill of driving and with intellectually demanding work; experiments have established that people intoxicated with cannabis are unable to carry out complex mental tasks.
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some evidence that heavy use by young people might trigger the mental illness schizophrenia in susceptible individuals.
Amphetamines
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man-made chemicals that include “Dexedrine”, “Speed” AND methamphetamine derivative called “Ecstasy”
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release two naturally occurring NTs:
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dopamine - explains the strong arousal and pleasurable effects of amphetamines.
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serotonin - account for ability to cause a sense of well-being and dream-like state (include hallucinations)
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Dexedrine and Speed promote mainly dopamine release, Ecstasy more serotonin
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more powerful hallucinogen d-LSD also acts on serotonin mechanisms in the brain
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Amphetamines are powerful psychostimulants and they can be dangerous - especially in overdose. Animal experiments have shown that Ecstasy can cause a prolonged, perhaps permanent reduction of serotonin cells
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Frightening schizophrenia like psychosis can happen after Dexedrine and Speed
Heroin
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man-made chemical derivative of the plant product morphine
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NTs known as endorphins (pain control) drugs copy their actions are valuable in med.
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injected/smoked (immediate) possibly due to an effect of endorphins on reward mechanisms
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highly addictive, as dependence develops, these pleasurable sensations quickly subside to be replaced by an incessant “craving”
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It is a very dangerous drug that can kill in even modest overdose (it suppresses breathing reflexes)
Cocaine
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plant-derived chemical can cause pleasurable sensations & powerful psychostimulant
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Like the amphetamines, cocaine makes more dopamine and serotonin available in the brain
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dangerous, users esp. of "crack", can become violent and agro, and life threatening risk of overdose
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cost can cause crime
Scientists found that when certain immature neurons are maintained in a dish with no other cell types, they produce the neurotransmitter norepinephrine.
In contrast, if the same neurons are maintained with specific cells, such as cardiac, or heart, tissue, they produce the neurotransmitter acetylcholine.
DEVELOPMENT



Diagram A:
GABAergic neurons migrating tangentially in the neocortex
4. some may be stationary
Diagram B:
GABAergic neurons migrating
1. Tangentially towards hippo
2. deflected towards the pial surface migrate radially
3. or with some angle to the radial axis
5. A part of these neurons may descend from the MZ to be integrated into CP
The governing principle of developmental biology is that the genome is a set of instructions for making an organ of the body, not a blueprint.
The genome is the 40,000 or so genes that orchestrate the process.
Neuroscientists studying brain development examine a wide variety of animals - zebrafish, frog, chick and mouse – each having advantages for examining particular molecular or cellular events.




The zebrafish embryo is transparent - allowing each cell to be watched under the microscope as it develops.
Chicks and frogs are less amenable to genetic studies, but their large embryos allow microsurgical manipulations - such as examining what happens when cells are moved to abnormal positions.
The mouse breeds rapidly - its genome has been mapped and almost completely sequenced.
Foot note: Sequence and map are both portraits of a genome, but a genome map is less detailed than a genome sequence. A sequence spells out the order of every DNA base in the genome, while a map simply identifies a series of landmarks in the genome.
Can find a gene but not sequence it.
We know what the genes do, just not how genes convert a sheet of cells into a working brain. It is one of the grand challenges of neuroscience.
Failure of the neural tube to close results in spina bifida, a condition that is usually confined to the lower spinal cord. While distressing, it is not lifethreatening.




By contrast, failure of closure at the head end can result in the complete absence of an organised brain, a condition known as Anencephaly.
1 in every 4,859 babies in the United States
There has been a 27% decline in pregnancies affected by neural tube defects (spina bifida and anencephaly) since the United States began fortifying grains with folic acid
But what if such a development program could be re-activated for cases of pathological neuronal loss?
Useful for:
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Alzh's
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Park’s
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SC damage W/ paralysis
SC dam. : axons can be encouraged to re-grow following injury but whether they can be made to re-connect appropriately remains an area of intense investigation.
Currently working to repair areas of the brain damaged by diseases such as Park’s using stem cells.

Encephalocele
sac-like protrusion or projection of the brain and the membranes that cover it through an opening in the skull. Encephalocele happens when the neural tube does not close completely during pregnancy. The result is an opening in the midline of the upper part of the skull, the area between the forehead and nose, or the back of the skull.
but sometimes a small encephalocele in the nose and forehead region can go undetected.
1 out of every 10,000 babies born in the United States each year will have encephalocele.
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Buildup of too much fluid in the brain
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Complete loss of strength in the arms and legs
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An unusually small head
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Uncoordinated movement of the voluntary muscles, such as those involved in walking and reaching
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Developmental delay
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Vision problems
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Mental and growth retardation
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Seizures
May be familial or due to lack of folic acid




signal to engage the gene, and therefore the final determination of the chemical messengers that a neuron produces, is influenced by factors coming from the location of the synapse itself.
saltatory conduction (the word “saltatory” means “to jump”), is responsible for the rapid transmission of electrical signals.
apoptosis, programmed cell death initiated in the cells. caused by:
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battle with other neurons to receive life-sustaining chemical signals called trophic factors
Factors are
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produce limited quantities by target tissues.
nerve growth factor is important for sensory neuron survival
injuries and some neurodegenerative diseases kill neurons not by directly inflicting damage but rather by activating the cells’ own death programs.
most neuronal cell death occurs in the embryo


