ch 6 section 3

___________ is estimated to be the primary neurotransmitter at 50 percent of the excitatory synapses in the CNS.

Glutamate

The IPSP is a ________graded potential that lessens the likelihood that the postsynaptic cell will depolarize to threshold and generate an action potential.

Hyperpolar

NE is found in both the CNS and PNS, while Epi is found mainly in the PNS. The adjective ____________ arises historically from nineteenth-century physiologists who referred to NE and Epi as noradrenaline and adrenaline, respectively

"adrenergic"

_____________is an important neurotransmitter in the CNS and PNS

Norepinephrine

Low doses of botulinum toxin _______ are injected therapeutically to treat a number of conditions, including facial wrinkles, severe sweating, uncontrollable blinking, misalignment of the eyes, and others.

(Botox)

The bacillus Clostridium tetani produces a toxin called ______ ______ which is a protease that destroys SNARE proteins in the presynaptic terminal so that fusion of vesicles with the membrane is prevented, inhibiting neurotransmitter release. Ultimately, this causes excess muscle contraction and a rigid or spastic paralysis

(tetanus toxin)

There are 2 subtypes of ionotropic glutamate receptors:

1. AMPA receptors (identified by their binding to α-amino-3 hydroxy-5 methyl-4 isoxazole proprionic acid), and 2. NMDA receptors (which bind N-methyl-D-aspartate).

neurotransmitters are involved in ___________________,

rapid communication

General factors that determine synaptic strength

1. area of synaptic contact 2. nerotransmitter reuptake 3. enzymatic destruction of neurotransmitter 4. geometry of diffusion pathway

Pre-synaptic factors that determine synaptic strength (4)

1. availability of neurotransmitter 2. amt of precursor molecules 3. axon terminals membrane potential 4. activates receptors on the terminal axon Ca2+

Possible actions of drugs on a synapse (4)

1. increase leakage of neurotransmitters- leads to breakdown of enzymes 2. increase neurotransmitters in cleft- more binding to receptors 3. inhibits, releases and synthesis of neurotransmitter 4. blocks enzymes needed to breakdown neurotransmitters

Postsynaptic factors that determine synaptic strength (3)

1. past history of electrical state 2. neurotransmitters act on postsynaptic neuron 3. Desensitization of receptors

To terminate the signal in a chemical synapse, the unbound neurotransmitters must be removed from the synaptic cleft. This is accomplished by: 1. 2. 3. 4.

1. reuptake- ATP back into the presynaptic neuron 2. Transport into Glial Cells- degrades 3. Diffusion away from receptor 4. Enzymatic transformation in inactive substances

Alzheimer's disease affects 10% to 15% of people over age ___, and 50% of people over age __.

65, 85

Because of the degeneration of cholinergic neurons, this disease is associated with a decreased amount of ___ in certain areas of the brain and even the loss of the postsynaptic neurons that would normally respond to it.

ACh

_______________ is a major neurotransmitter in the PNS at the neuromuscular junction and in the brain.

Acetylcholine (ACh)

________________ protein that breaks down ACh

Actycholinesterase

Many cholinergic neurons in the brain degenerate in people with _________ ________, a brain disease that is usually age related and is the most common cause of declining intellectual function in late life.

Alzheimer's disease

_________ destroys snare proteins that causes reduced muscle contraction and paralysis

Botulism

changes in the brain

Brains show dramatic shrinkage from cell loss and widespread debris This may start 20 years or more before diagnosis Synapses begin to fail due to : Accumulation of beta-amyloid (call beta-amyloid plaques); this occurs OUTSIDE the neurons Interferes with neuron-to-neuron communication at synapses and causes cell death Accumulation of the protein tau (called tau tangles) INSIDE neurons Tau tangles block the transport of nutrients and other essential molecules

The amino acid neurotransmitters are by far the most prevalent neurotransmitters in the _____, and they affect virtually all neurons there.

CNS

_____________-- _______________ are found in widespread locations throughout the CNS and PNS in pathways regulating a wide range of physiological functions including appetite, pain sensation, mood, memory, and locomotor activity.

Cannabinoid receptors

Biogenic amines

Catecholamines Dopamine (DA) Norepinephrine (NE) Epinephrine (Epi) Serotonin (5-hydroxytryptamine, 5-HT) Histamine

__________ __________ low amount of copper, iron and zinc are disrupted in AD; could affect tau, APP, and APOE

Cellular hypothesis

Neurons that release ACh are called __________neurons.

Cholinergic

_________________ __________ AD is caused by reduced synthesis of neurotransmitter acetylcholine

Cholinergic hypothesis

_________ during the action potential opens voltage-gated Ca^(2+) channels in the plasma membrane of the axon terminal, and Ca^(2+) flows into the neuron

Depolarization

Excitatory chemical synapses generate an _________________________________

Depolarizing effect

Examples of neuropeptides include:

Endogenous opioids Beta-endorphin Dynorphins Enkephalins Morphine and codeine are synthetic opioids that are used as analgesics (pain reducers)

____________ another biogenic amine, is not a common neurotransmitter in the CNS, but it is the major hormone secreted by the adrenal medulla.

Epinephrine,

Amino acids

Excitatory amino acids; for example, glutamate Inhibitory amino acids; for example, gamma-aminobutyric acid (GABA) and glycine

Purines

For example, adenosine and ATP

Neuropeptides

For example, endogenous opioids, oxytocin, tachykinins

Gases

For example, nitric oxide, carbon monoxide, hydrogen sulfide

Although it is not one of the 20 amino acids used to build proteins, it is classified with the amino acid neurotransmitters because it is a modified form of glutamate.

GABA

Synapses that use _______ are also among the many targets of the ethanol found in alcoholic beverages.

GABA

_________neurons in the brain are small interneurons that dampen activity within neural circuits. Postsynaptically, GABA may bind to ionotropic or metabotropic receptors.

GABA

Amino acid neurotransmitters at inhibitory synapses include _______and ___________.

GABA and glycine

________ ______ _________ (LSD) stimulates the 5-HT2A subtype of serotonin receptor in the brain, causing intense visual hallucinations.

Lysergic acid diethylamide

Neuroeffector Communication

Many neurons of the PNS synapse not on other neurons but at neuroeffector junctions on muscle, gland, and other cells. The events that occur at neuroeffector junctions are similar to those at synapses between neurons. The neurotransmitter is released from the efferent neuron upon arrival of an action potential, diffuses to the surface of the effector cell, and binds to receptors on that cell's plasma membrane. The receptors on the effector cell may be either ionotropic or metabotropic.

_________ ___________ poor functioning blood brain barrier allows for Herpes simplex virus type 1 and/or chronic bacterial infections

Neurovascular hypothesis

_______ _________damages nerve processing and leads to tau deposits

Myelin breakdown

_____________ also may change the presynaptic cell's synthesis, release, reuptake, or metabolism of a transmitter.

Neuromodulators

_______________ often modify the postsynaptic cell's response to specific neurotransmitters, amplifying or dampening the effectiveness of ongoing synaptic activity.

Neuromodulators

____________ are composed of two or more amino acids linked together by peptide bonds. About 100 neuropeptides have been identified, but their physiological functions are not all known.

Neuropeptides

___________ _________ in the brain are important in cognitive functions and behavior. The presence of nicotinic receptors on presynaptic terminals in reward pathways of the brain explains why tobacco products are among the most highly addictive substances known

Nicotinic receptors

Gases are not released by exocytosis of presynaptic vesicles, nor do they bind to postsynaptic plasma membrane receptors. They are produced by enzymes in axon terminals (in response to Ca^(2+) entry), and simply diffuse from their sites of origin in one cell into the intracellular fluid of other neurons or effector cells, where they bind to and activate proteins. Examples include:

Nitric oxide Carbon monoxide Hydrogen sulfide

Alzheimers disease amygdala

Part of brain that manages emotions During AD, damage to this region causes: Emotional instability Fear Anger Mood swings Paranoia Temper Anxiety

Alzheimers disease brain stem

Progressive damage to brain stem causes changes in: Sleep patterns Trouble swallowing Erratic blood pressure Heart arrhythmia

Calcium ions activate processes that lead to the fusion of docked vesicles with the synaptic terminal membrane, and their interaction with _____ _______

SNARE proteins.

Some chemical weapons, such as the nerve gas ________, inhibit acetylcholinesterase, causing a buildup of ACh in the synaptic cleft

Sarin

_________ is produced from tryptophan, an essential amino acid

Serotonin

_________(5-hydroxytryptamine, or 5-HT) is a neuromodulator involved at virtually every structure in the brain and spinal cord and operates via at least 16 different receptor subtypes

Serotonin

Mechanism of Long-Term Potentiation

Step 1. Presynaptic neuron fires action potentials. Step 2. Glutamate is released from presynaptic terminals. Step 3. Glutamate binds to both AMPA and NMDA receptors on postsynaptic membranes. Step 4. Depolarizing EPSP of the postsynaptic cell mediated via AMPA channels ( influx). Step 5. The depolarization through the AMPA channels allows the magnesium ion blocking the NMDA channels to move and activate the channel. NMDA-receptor channels mediate a substantial influx. Step 6. Calcium enters the cell. Step 7. Calcium ions activate second-messenger systems in the postsynaptic cell that includes persistent activation of multiple protein kinases, stimulation of gene expression and protein synthesis, and an increase in sensitivity of the postsynaptic neuron to glutamate. Step 8. This second-messenger system can also activate long-term enhancement of presynaptic glutamate release via retrograde signals that have not yet been identified

What is Tau Protein?

Tau helps to support neuron cytoskeleton Cytoskeleton has microtubules When phosphorylated, tau stabilizes microtubules In AD, becomes hyperphosphorylated and threads/tangles form

What is Amyloid Beta?

Transmembrane protein Important for neuron growth, survival, and repair In AD, 2 enzymes (gamma secretase and beta secretase) cause APP to be broken into small pieces These small pieces clump and form deposits known as plaques.

Benzodiazepine drugs such as _____________ and _____________ reduce anxiety, guard against seizures, and induce sleep by increasing flux through the GABA receptor.

alprazolam (Xanax) and diazepam (Valium

The biogenic amines are small, charged molecules that are synthesized from ____________.

amino acids

Amino acid neurotransmitters at excitatory synapses include ____________ and ___________.

asparte, glutamate

Toxins of the Clostridium botulinum bacilli, which cause _________, also block neurotransmitter release from synaptic vesicles by destroying SNARE proteins. They target excitatory synapses that activate skeletal muscles; botulism is characterized by reduced muscle contraction, or a flaccid paralysis

botulism

These defects and those in other neurotransmitter systems that are affected in this disease are related to the __________________-.

declining language and cognitive abilities, confusion, and memory loss that characterize individuals with Alzheimer's disease

Approximately 90% of the body's total serotonin is found in the _________ ___________, 8% is in ___________ _______ ____ ______ ________, and only 1% to 2% is found in the _________

digestive system, blood platelets and immune cells, brain

Catecholamines, including _____________, ____________-- and _______________ all contain a catechol ring and an amine group, which is why they are called ____________They are formed from the amino acid tyrosine.

dopamine, norepinephrine, and epinephrine/ catecholamines

The most common biogenic amines are

dopamine, norepinephrine, serotonin, and histamine

______________ stimulates GABA synapses and simultaneously inhibits excitatory glutamate synapses, with the overall effect being global depression of the electrical activity of the brain.

ethanol

Serotonin has an _____effect on pathways that are involved in the control of muscles, and an inhibitory effect on pathways that mediate sensations.

excitatory

The EPSP is a __________graded potential that decreases in magnitude as it spreads away from the synapse by local current. Its only function is to bring the membrane potential of the postsynaptic neuron closer to threshold.

excitatory

Normal function of glycinergic neurons is essential for maintaining a balance of ___________ and __________ activity in spinal cord integrating centers that regulate skeletal muscle contraction.

excitatory and inhibitory

Neurotransmitters are released via _________

exocytosis.

_________ is the major neurotransmitter released from inhibitory interneurons in the spinal cord and brainstem. It binds to ionotropic receptors on postsynaptic cells that allow 〖"Cl" 〗^− to enter.

glycine

_______ is made from the amino acid histidine.

histamine

Inhibitory chemical synapses generate an ____________________________________

hyperpolarizing affect: lessons the chance of depolarizing

neuromodulators tend to be ________________________________such as learning, development, and motivational states.

involved in slower events

Receptors for neurotransmitters influence ____ ________ that directly affect excitation or inhibition of the postsynaptic cell, and these mechanisms operate within milliseconds

ion channels

The ___________ ______________ increases flux into the cell, resulting in hyperpolarization (an IPSP) of the postsynaptic membrane.

ionotropic receptor

All adrenergic receptors are __________________ and thus use second messengers to transfer a signal from the surface of the cell to the cytoplasm

metabotropic

The catecholamine neurotransmitters are broken down in both the extracellular fluid and the axon terminal by enzymes such as __________ ___________

monoamine oxidase (MAO).

ACh binds to __________(G protein-coupled) or __________ (ligand-gated ion channel) receptors.

muscarinic , nicotinic

Receptors for________________ bring about changes in metabolic processes in neurons. Such changes can occur over minutes, hours, or even days and include alterations in enzyme activity or, through influences on DNA transcription, in protein synthesis.

neuromodulators

Adrenergic receptors are utilized by the ________________ __________________ and ____________________

neurotransmitters norepinephrine (NE), epinephrine (Epi)

This results in _________ of postsynaptic ACh receptors initially causing uncontrolled muscle contractions, but ultimately leading to receptor desensitization and paralysis.

overstimulation

Selective serotonin reuptake inhibitors such as ____________ (Paxil) are thought to aid in the treatment of depression by inactivating the presynaptic membrane 5-HT transporter, which mediates the reuptake of serotonin into the presynaptic cell.

paroxetine

In addition to the GABA binding site, this receptor has several additional binding sites for other compounds, including:

steroids, barbiturates, and benzodiazepines.

This becomes apparent in cases of poisoning with the neurotoxin ______, an antagonist of glycine receptors. Victims experience hyperexcitability throughout the nervous system, which leads to convulsions, spastic contraction of skeletal muscles, and ultimately death due to impairment of the muscles of respiration.

strychnine

Axon terminals of the presynaptic neuron hold the ________ _________ that contain neurotransmitter molecules.

synaptic vesicles

________destroys snare proteins that causes excess muscle contraction and paralysis

tetanus

These receptors are the principal target of _____________________________ the principal psychoactive constituent of plants in the Cannabis genus.

tetrahydrocannabinol (THC),