Neuro: Synapses
A. Disorders of neurotransmitter metabolism account for a large variety of neurologic and psychiatric illnesses, but in many cases the etiology is not well understood. B. Some examples are given below:
...
NEUROMUSCULAR JUNCTION
...
partly on the amount of neurotransmitter released into the synapse.
...
D.
During synaptic transmission, the neurotransmitter is released from the presynaptic element, diffuses across the synaptic cleft, and then binds with specific receptors on the postsynaptic membrane.
...
E. Alzheimer's disease
2.
After about 2 months, degenerative changes also begin to appear in the muscle fibers themselves.
1.
At one time it was believed that type I synapses were excitatory in function and type II synapses were inhibitory.
V.
BRIEF OVERVIEW OF SYNAPTIC FUNCTION
C.
Ca2+ enters and promotes the fusion of synaptic vesicles with the release site of the presynaptic membrane.
B.
Characteristics of type I and type II synapses
2.
Cortical neurons normally receive terminals from cholinergic neurons (neurons that release acetylcholine) in the basal forebrain nuclei. In Alzheimer's disease, these terminals are lost and the activity of choline acetyltransferase (the enzyme responsible for acetylcholine synthesis) in the cortex and hippocampus of diseased patients is extremely low.
...
D. Bipolar disorder
a.
Dense material is present and obvious on the postsynaptic membrane but NOT on the presynaptic membrane (so that the synapse is visibly asymmetrical).
a.
Dense material is thin and present on BOTH the presynaptic and the postsynaptic membranes (so that the synapse appears symmetrical).
a.
Each synaptic vesicle contains a fixed amount of neurotransmitter (called a quantum), so the amount of neurotransmitter released depends on the number of vesicles that fuse with the presynaptic membrane in response to Ca2+ influx.
...
F. Myasthenia gravis
B.
Motor axons may branch extensively and innervate as few as 10 muscle fibers or as many as 500 or more.
1.
Myelinated motor nerves branch within the perimycium and each gives rise to several terminal twigs.
IV.
NEUROTRANSMITTERS
D.
Neurotransmitter is released into the synaptic cleft by exocytosis where it then diffuses and binds to ligand-gated receptors on the postsynaptic membrane.
A.
Neurotransmitter release is initiated by the arrival of an action potential, which depolarizes the presynaptic terminal.
1.
In MG, the patient's immune system produces antibodies to the nicotinic acetylcholine receptor.1
B.
In many cases, neurotransmitters are stored in and released from the synaptic vesicles in the axon terminal.
c.
In the PNS, the postsynaptic element may be a skeletal muscle cell (myoneural junction) or the cells of a gland.
A.
In the early years of electron microscopy, two basic morphologic types of synapse became apparent. They were named Gray type I and Gray type II synapses. They are also know as asymmetrical and symmetrical synapses, respectively.
3.
In the final stages, most of the muscle fibers are completely destroyed and replaced by fibrous and fatty tissue; this fibrous tissue has a tendency to continue to shorten for many months - a process called contracture.
B.
In the terminal, depolarization causes voltage-gated calcium channels to open.
Describe the process that occurs in a chemical synapse
In the type of synapse known as a chemical synapses, a substance, the neurotransmitter, diffuses across the narrow space between the two cells and becomes bound to receptors, which are special protein molecules that reside in the postsynaptic membrane.
A.
Neurotransmitters are the means by which information is exchanged among nerve cells as well as between nerve cells and effector cells (muscle or glands)
C.
Neurotransmitters may be biogenic amines (acetylcholine [Ach], dopamine, norepinephrine), amino acids (glutamate, ã-aminobutyric acid [GABA]), nucleotides (adenosine), or neuropeptides (substance P, cholecystokinin, somatostatin).
3.
Nevertheless, the scheme is still useful: synapses using acetylcholine often have the Gray type I morphology and are excitatory, whereas those using ãaminobutyric acid (GABA) usually resemble Gray's type II synapses and are inhibitory.
1.
Note: Neurotransmitters will be not be covered in detail; consult the Neurophysiology or Pharmacology portions of your curriculum.
2.
Noted primarily for the ability to reduce the appearance of some facial wrinkles, Botox injections are also used to treat such problems as repetitive neck spasms (cervical dystonia), excessive sweating (hyperhidrosis), overactive bladder and some causes of crossed eyes. Botox injections may also help prevent chronic migraines in some people.
Near the "contact" with another nerve cell, the membrane is specialized to form the BLANK
presynaptic membrane.
There is a correlation between vesicle shape and function: what is it?
round vesicles appear to contain excitatory neurotransmitters while the flattened type of vesicle contains an inhibitory neurotransmitter.
THIS constitutes the functional coupling between two or more neurons
synapse
The presynaptic element formed by axons is called by several different names: give 4
synaptic terminal, terminal button, bouton termineaux, or terminal end-bulb.
These are small vesicles (bags) that contain the neurotransmitter substance released at the synapse.
synaptic vesicles
The presynaptic element contains what two organelles?
synaptic vesicles and mitochondria.
2.
Patients have blurred vision and double vision, dilated pupils, ptosis (drooping eyelids), slurred speech, difficulty swallowing, dry mouth, autonomic paralysis, and widespread weakness.
E.
Some neurotransmitters appear to be consistently either excitatory (i.e., glutamate) or inhibitory (i.e., GABA), but the effect (excitation or inhibition) of a neurotransmitter on a responsive postsynaptic neuron is not due to any inherent property of the neurotransmitter molecule itself, but rather to the nature of the specific receptor on the postsynaptic membrane.
b.
Synaptic cleft is 20 nm wide.
b.
Synaptic cleft is 30 nm wide.
d.
Synaptic region less than 1 ìm long. C. Functional correlation with morphology
d.
Synaptic region up to 1- 2 ìm long.
c.
Synaptic vesicles are oval, flattened, or pleiomorphic (variable) in shape.
c.
Synaptic vesicles are round and large (30-60 nm), with clear centers.
d.
The membrane of the postsynaptic element typically has dense material adjacent to its inner surface. The differing appearance of the presynaptic and postsynaptic dense material has lead to the classification of synapses into Gray type I (asymmetric synapse) and Gray type II (symmetric synapse; see below).
What determines whether the effect produced by a receptor will be one of excitation or inhibition of the postsynaptic cell?
The nature of the receptor molecule determines whether the effect produced will be excitation (depolarization) or inhibition (hyperpolarization) of the postsynaptic cell; some synapses are, therefore, excitatory, and others are inhibitory.
2.
The nerve loses its myelin sheath and forms a dilated termination (terminal bouton) that sits within a trough (synaptic trough, primary synaptic cleft) on the muscle cell surface.
A.
The neuromuscular junction is the chemical synapse between a motor nerve terminal and a muscle fiber.
2.
The neurons of SN begin dying at an accelerated rate and the loss of dopamine results in a characteristic resting tremor and the inability to properly control movement.
F.
The opened ion channels in the postsynaptic membrane may then lead to depolarization and an action potential generated in the postsynaptic cell.
b.
The postsynaptic element in the CNS is typically a dendrite (axodendritic synapse), but it may be on the cell body (axosomatic synapse) or even another axon (axoaxonic synapse).
THIS is a cell or part of a cell that the presynaptic elements forms a synapse with
The postsynaptic element.
e.
The postsynaptic membrane possesses receptors on the plasma membrane that bind neurotransmitters.
1.
This disease affects the dopamine-synthesizing neurons located in the substantia nigra (SN) of the midbrain.
1.
This disease is characterized by the degeneration of neurons in basal forebrain nuclei, the loss of synapses in the cerebral cortex and hippocampus, and the presence of pathologic structures call neurofibrillary tangles and senile plaques.
1.
This disorder appears to be caused by imbalances in the phosphatidyl inositol (PI)-linked neurotransmitter systems.
a.
This is because only the presynaptic cell releases the neurotransmitter and only the postsynaptic cell expresses the receptor protein.
2.
This receptor is a ligand-gated channel found at the synapse between primary motor neurons and skeletal muscle fibers.
Describe the appearance of synaptic vesicles
Vesicles range in size from 300 - 600 nm in diameter, and may appear to be round or flattened.
2.
We now know that the excitatory or inhibitory function of a synapse depends on the nature of the receptors present on the postsynaptic membrane and cannot be reliably predicted from the ultrastructural characteristics.
1.
When skeletal muscle loses its nerve supply (it is denervated), it no longer receives the contractile signals that are required to maintain normal muscle size, therefore, denervated muscles begins to atrophy almost immediately.
1.
Whether or not a neurotransmitter functions to excite or inhibit the postsynaptic cells is dependent on the receptor, not the neurotransmitter. The same neurotransmitter may either be excitatory or inhibitory.
In the PNS, an important type of chemical synapse is that between a neuron and skeletal muscle, called THIS
neuromuscular junction.
(NMJ, myoneural junction, motor end-plate)
...
1. Chemical synapses are unidirectional; they transmit information only in the direction from the presynaptic cell to the postsynaptic cell.
...
Describe how the width of the synaptic cleft varies depending on the following types of synapses: 1. neuronal 2. neuromuscular for skeletal muscle 3. myoneuronal junctions for smooth muscle
1. 20 nm in width at neuronal synapses 2. 50 nm at neuromuscular junctions for skeletal muscle 3. 400 nm at myoneural junctions involving smooth muscle.
...
1. A motor neuron and the muscle fibers it innervates constitute a motor unit.
...
1. Gray type I (asymmetrical)
In general, there are two broad morphologic categories of synapses, BLANK and BLANK. The vast majority of synapses in the mammalian CNS are of THIS type
1. chemical and electric 2. chemical
The prototypical chemical synapse consists of what three things?
1. presynaptic element, 2. postsynaptic element, and the 3.intervening space (the synaptic cleft).
THIS membrane has dense material adjacent to its inner surface that may serve to guide synaptic vesicles to the presynaptic membrane, where synaptic vesicles then release the transmitter into the synaptic cleft.
1. presynaptic membrane
...
2. Gray type II (symmetrical)
E.
Binding of the neurotransmitter with the receptor causes the receptor to change its shape, which results in opening of the receptor or activation of intracellular messengers associated with the receptor.
3.
Binding of these antibodies to the receptor results in pathologic destruction of the neuromuscular junctions, which in turn causes the muscle weakness characteristic of this disease.
F.
Biogenic amines (acetylcholine) and amino acid neurotransmitters (GABA) are synthesized in the axon terminal, although the enzymes necessary for their synthesis are produced in the cell body and shipped to the terminal by axonal transport. The axon lacks the machinery to synthesize proteins (or membrane lipids) and thus must obtain these materials from the cell body. Thus, axonal transport is always necessary to support synaptic function.
1.
Botox injections are a group of medications that use forms of botulinum toxin to temporarily paralyze muscle activity.
1.
Botulism is a serious paralytic illness caused by a nerve toxin that is produced by the bacterium Clostridium botulinum.
...
C. Parkinson's disease
1.
For example, neurons that respond to the neurotransmitter dopamine can express either of two types of dopamine receptor, D1 or D2. Binding of dopamine to the D1 receptor results in excitation while binding of dopamine to the D2 receptor results in inhibition.
...
G. botulism
I.
GENERAL
...
H. Botox
...
I. Effects of denervation (loss of synapses) of muscle
a.
If a neurotransmitter binds to ligand channels such as those for Na+ or Ca2+, then Na and/or Ca flows into the cell and results in depolarization (an EPSP - excitatory postsynaptic potential).
b.
If a neurotransmitter such as GABA binds to a receptor, then ligand-gated Cl- channels are opened, Cl- flows into the cell and results in hyperpolarization (IPSP - inhibitory postsynaptic potential). G. Two functional properties of chemical synapses:
2.
It is thought that a pathologic imbalance in PI turnover may result in mood changes. Drugs such as lithium carbonate stabilize PI turnover, thereby stabilizing the patient's mood.
III.
MORPHOLOGIC CLASSIFICATION OF CHEMICAL SYNAPSES
4.
Recovery occurs by sprouting of the nerve terminals and formation of new junctions.
VI.
SOME DISORDERS RELATED TO SYNAPSES AND NEUROTRANSMITTER METABOLISM
II.
STRUCTURE OF TYPICAL NEUROMUSCULAR JUNCTION A. axon terminal
3.
The axon terminal contains numerous mitochondria and 40-60 nm synaptic vesicles which contain acetylcholine - ACh.
2.
The strength of the effect on the postsynaptic membrane is variable and depends
THIS is the space that separates pre- and postsynaptic synaptic membranes
The synaptic cleft
3.
The toxin binds irreversibly to the nerve terminal at the neuromuscular junction and prevents release of ACh vesicles by some unknown mechanism.
Vesicles are often aggregated near sites on the presynaptic membrane called BLANK
active sites (or zones).
The most common type of CNS synapse comprises of what? an axon terminal of one neuron that is apposed to a dendrite (or dendritic spine) of a second neuron.
an axon terminal of one neuron that is opposed to a dendrite (or dendritic spine) of a second neuron.
Most drugs that affect the central nervous system act where?
at the synapse
