Chapter 2: The Neuron, Synaptic Transmission, and Neurotransmitters Flashcards
Human Nervous System Consists of Two Divisions?
- Central nervous system (CNS)
-brain and spinal cord - Peripheral nervous system (PNS)
-nerves that originate in the spinal cord and connect to organs in the body
-contains automatic and sympathetic nervous systems
-should pay attention to effects of drugs on autonomic nervous system
most drugs block effects of which system?
parasympathetic nervous system
what is the function of the Spinal Cord?
Made up of neurons and fiber tracts that:
-sensory information
-motor output flow
-provide autonomic (involuntary) control of vital body organs
-contains the reflex arc
three neurons in reflex arc?
- Inner Neuron- connects horns
- Sensory Neuron
- Motor Output Neurons
Primary divisions of the brain?
- Hindbrain
- Midbrain
- Forebrain
what is the definition of the spinal cord?
Information highway of structures/messages sent back and forth from spinal cord to rest of body
how are human brain more evolved than other mammals?
it is not that our brains are different but rather we have tighter control over the same functions
what is The brain stem ?
the portion of the brain consisting of the medulla, pons, and midbrain, which connects the spinal cord to the forebrain
what is the cerebellum?
Behind the brain stem is a large, bulbous structure—the cerebellum. A highly convoluted structure, the cerebellum is connected to the brain stem by large nerve tracts. The cerebellum is necessary for the proper integration of movement and posture.
most of the drugs effect which portions of the brain?
the lower brain systems
including the side effects on the para/sympathic nervous systems as well
Most of neurons in which nuceli contain dopamine?
substantia nigra and ventral tegmental area (VTA) in the forebrain
What is the Limbic System?
Second major subdivision of the telencephalon
Amygdala and the hippocampus
Contributes to regulation of mood, affect, emotion, responses to emotional experiences
Reward circuit
which two cells make up the Central nervous system?
- Neurons
- Non-Neural Cells aka GLIAL cells
Each occupy about 50% of the volume
However, there are 10x more glial cells because they are 1/10the the size of neurons
explain functions of each of the glial cells.
- oligodendrocytes
-providing myelin
-in communications with the axons, shuttling lactate back to the axon for respiratory processes - astrocytes
-forming blood brain barrier
-supports neurons by soaking up toxic compounds around cytoplasm - microglial cells (or ependymal)
-acts as a immune system for the CNS despite the CNS not really having one
How do we get neurotransmitters?
Through Synthesis
(by altering or building upon simpler molecules)
What is synthesis?
Formation of transmitters
STEPS:
1. Precursors are the main ingredient
-Brought to the neuron by the bloodstream
-Taken up by cell body and/or terminal
- Enzymes put the ingredients together
-converted from amino acid into neurotransmitter
what are the precursors to neurotransmitters? how do they get into the CNS?
amino acid
they get in through transportation because they are large molecules which are polar
what are the 3 parts of a neuron?
- cell body (soma)
-endoplasmic reticulum (folded membranes, smooth/rough)
-nucleus (DNA)
-ribosomes (transport genetic codes)
-mitochondria
-cytoplasm (jelly like substance)
-golgi complex (modifies and packages neurons) - dendrites
-specialized RECIEVING apparatus of the cell
-contains receptors - axon
-transmitting apparatus of the cell
-usually branches into many terminals
-can be myelinated or unmyelinated
what are receptors?
protein complexes that cross the membrane
THOUSANDS across cell surface
all inputs are being summed as an electrical potential of the axon helic (the point at which the axon leaves the cell body) these are the electrical channels which start the channel
what allows for fast transportation between the myelin?
the gaps or nodes
-needed to regenerate the action potential
-fast transmission
it is efficient to only need to pump ions in the gaps rather than the entire myelin (unmyelinated axons do not have this)
illustrate the basics of synaptic transmission.
- action potential is transmitted down axon to presynaptic terminal
- the depolarization at the presynaptic terminal opens ion channels for calcium to enter ion
- calcium enters vessles (containing neurotransmitters) to fuse with membrane and open/release transmitter molecules into the synaptic cleft
- After release, neurotransmitter molecules bind to and activate receptors on the pre- and postsynaptic membrane (entirely based on diffusion)
- Transmitter effects are terminated either by breakdown of transmitter within the synaptic cleft or by reuptake back into the axon terminal to be recycled
how are neurotransmitters released into vesicles?
through process of Exocytosis
where Vesicles fuse with presynaptic membrane and release transmitters into the synapse
what is known as “binding”?
Attachment of transmitter to receptor
Different Varieties of Neurotransmitter Receptors?
- Ionotropic
-ion channel
-fast response - Metabotropic, or G protein-coupled
-Initiates a second signal (messenger) inside the neuron
-do not form ion pore
Different Inactivations/Terminations of Synaptic Transmission?
- Metabolism
-enzymes in synapse that break transmitter down - Re-uptake
-transporter proteins transport it back
these processes help terminate the signal and cell to conserve energy by allowing recycling
how is glutamate handled in extracellular fluid?
taken up by astrocytes
what is meant by Receptor Specificity?
Each receptor is specific for a particular neurotransmitter
Each neurotransmitter binds to several receptor subtypes which can produce different effects
how does the neuron communicate across the synapse?
scientists have been divided by it being either electrical or neurochemical.
it was shown to be neurochemical
first neurotransmitter to meet the defined criteria? what is it?
Acetylcholine (ACh)
-easiest to study
-found in CNS, synapses in sympathetic systems, neuromuscular junction
-via choline from diet
describe the Acetylcholine (ACh) Synapse.
ACh is made in the axon terminal from acetyl coenzyme A (acetyl CoA) and choline and stored in vesicles for release.
After release, ACh binds to its receptors and is immediately broken down at the receptors by acetylcholinesterase (AChE) into choline and acetate.
the 2 Cholinergic Receptors?
- Nicotinic
-very fast - Muscarinic
-not fast
Where Is ACh Produced?
(1) The forebrain cholinergic complex composed of neurons in the medial septal nucleus and nucleus basalis which projects to the telencephalon
(2) the midbrain cholinergic complex, composed of cells in the pedunculopontine and laterodorsal tegmental nuclei, which ascends to the thalamus and other diencephalic loci (not shown) and descends to the pons, medulla, cerebellum, and cranial nerve nuclei.
what is Acetylcholine (ACh) used for?
reward (nicotinic receptors) and memory
part of the synapses of the sympathetic systems
process of Inactivation of ACh?
accomplished by Acetylcholinesterase (AChE)
After action in postsynaptic cleft, AChE degrades ACh to choline and acetate, which are taken back up into the neuron
AChE Inhibitors are can often be either..
- Irreversible and Toxic
-Include pesticides and nerve gases - Reversable
-trying to treat Alzheimer’s
-used as Cognitive enhancers
what are Catecholamines?
neurotransmitter with centre of structure containing a catechol ring
process of the Catecholamines?
- Synthesis starting with precursor amino acid tyrosine
-Tyrosine, an amino acid found in foods, is brought in from blood ans converted into dopa, then into dopamine in 2 steps
Next it is converted into norepinephrine, and finally (in the peripheral nervous system) into epinephrine, depending on which enzymes - termination by either reuptake or Monoamine oxidase (MAO)
-reuptake (transporter proteins) is the primary means
-enzymatic breakdown from Monoamine oxidase (MAO) located in presynaptic terminals
what does Tyrosine hydroxylase (TH) do?
what is this step known as?
what does this mean?
convert tyrosine to dopa
known as a rate limiting step
-as dopa goes down, this enzyme goes down
it means you cannot add tyrosine to enhance levels of dopamine or norepinephrine because of the rate limiting step
what does the enzyme dopamine β-hydroxylase (DBH) do?
convert dopamine into norepinephrine
which two pathways are found in lowbrain and have wide spread to the forebrain?
dopamine and norepinephrine
explain the pathway of norepinephrine.
Projects from brainstem to cortex, limbic system, hypothalamus, and cerebellum
part of brains back up system (backing up from something)
-typically in depression and anxiety
Produces an alerting, focusing, orienting response, positive feelings of reward, and analgesia
explain the pathway of dopamine.
three classic circuits
1. Hypothalamus to pituitary gland
MOST IMPORTANT
2. Substantia nigra to basal ganglia
3. Ventral tegmental area (VTA) to cortex and limbic system
*these two are found in midbrain
-all of these mechanisms are part of the “feeding forward” which psychologists call operant and classical conditioning, and moves us toward biologically stimulating information
dopamine produces a “push towards”
Norepinephrine receptors come in two families:
α – α1 & α2
β – β1, β2 & β3
ALL Dopamine receptors come in two families:
D1: postsynaptic
D2: presynaptic
DA and NE do not directly activate ion channels
how are dopamine and norepinephrin receptors metatropic?
DA and NE do not directly activate ion channels
The DA autoreceptor is…
D2 subtype
the NE autoreceptor is…
α2 subtype
what do the autoreceptors do?
The autoreceptors enhance the opening voltage-gated K+ channels
explain the process of the neurotransmitter Serotonin ((indoleamine transmitter)
Synthesis begins with Tryptophan
*No rate limiting step
There are many receptors (which are mainly Ionotropic)
The pathways start at the brain stem through base of midbrain
Axons in low brain have long axons projecting to the forebrain
explain the process of the neurotransmitter Serotonin ((indoleamine transmitter)
Synthesis begins with Tryptophan
*No rate limiting step
There are many receptors (which are mainly Ionotropic)
The pathways start at the brain stem through base of midbrain
Axons in low brain have long axons projecting to the forebrain
explain the process of the neurotransmitter Serotonin ((indoleamine transmitter)
Synthesis begins with Tryptophan
*No rate limiting step
There are many receptors (which are mainly Ionotropic)
The pathways start at the brain stem through base of midbrain
Axons in low brain have long axons projecting to the forebrain
explain the process of the neurotransmitter Serotonin ((indoleamine transmitter)
Synthesis begins with Tryptophan
*No rate limiting step
There are many receptors (which are mainly Ionotropic)
The pathways start at the brain stem through base of midbrain
Axons in low brain have long axons projecting to the forebrain
explain the process of the neurotransmitter Serotonin ((indoleamine transmitter)
Synthesis begins with Tryptophan
*No rate limiting step
There are many receptors (which are mainly Ionotropic)
The pathways start at the brain stem through base of midbrain
Axons in low brain have long axons projecting to the forebrain
explain the process of the neurotransmitter Serotonin ((indoleamine transmitter)
Synthesis begins with Tryptophan
*No rate limiting step
There are many receptors (which are mainly Ionotropic)
The pathways start at the brain stem through base of midbrain
Axons in low brain have long axons projecting to the forebrain
explain the process of the neurotransmitter Serotonin ((indoleamine transmitter)
Synthesis begins with Tryptophan
*No rate limiting step
There are many receptors (which are mainly Ionotropic)
The pathways start at the brain stem through base of midbrain
Axons in low brain have long axons projecting to the forebrain
explain the process of the neurotransmitter Serotonin ((indoleamine transmitter)
Synthesis begins with Tryptophan
*No rate limiting step
There are many receptors (which are mainly Ionotropic)
The pathways start at the brain stem through base of midbrain
Axons in low brain have long axons projecting to the forebrain
explain the process of the neurotransmitter Serotonin ((indoleamine transmitter)
Synthesis begins with Tryptophan
*No rate limiting step
There are many receptors (which are mainly Ionotropic)
The pathways start at the brain stem through base of midbrain
Axons in low brain have long axons projecting to the forebrain
explain the process of the neurotransmitter Serotonin ((indoleamine transmitter)
Synthesis begins with Tryptophan
*No rate limiting step
There are many receptors (which are mainly Ionotropic)
The pathways start at the brain stem through base of midbrain
Axons in low brain have long axons projecting to the forebrain
explain the process of the neurotransmitter Serotonin ((indoleamine transmitter)
Synthesis begins with Tryptophan
*No rate limiting step
There are many receptors (which are mainly Ionotropic)
The pathways start at the brain stem through base of midbrain
Axons in low brain have long axons projecting to the forebrain
explain the process of the neurotransmitter Serotonin ((indoleamine transmitter)
Synthesis begins with Tryptophan
*No rate limiting step
There are many receptors (which are mainly Ionotropic)
The pathways start at the brain stem through base of midbrain
Axons in low brain have long axons projecting to the forebrain
what is tryptophan?
amino acid you get from diet
enzyme breaks it down into 5-HT (symbolized as serotonin)
why is it possible to enhance serotonin by taking more dietary tryptophan?
because there is no rate limiting step
explain the process of neurotransmitters Glutamate and GABA.
Both have their basis in the amino acid glutamine
-One is Excitatory: Glutamate
-Other is Inhibitory: GABA
describe the processes in the glutamate synapse.
Glutamate (Glu) is released into the synapse and recaptured by excitatory amino acid transporters (EAATs) located on the presynaptic terminal and on adjacent glial cells.
Within the glial cells, glutamate is converted to glutamine (Gln) by the enzyme glutamine synthetase.
Glutamine diffuses back into neuronal terminals to replenish the Glu after conversion by the enzyme glutaminase and storage by Vesicular Glutamate Transporters.
The “fast” (ionotropic) receptors, NMDA, AMPA, and kainate are shown on the postsynaptic membrane; the “slow” (metabotropic) receptors are shown on both the pre- and postsynaptic membranes.
Two major receptors for glutamate?
What do they have in common?
- Kainate
- AMPA
They have in common that they both allow inflow of positive ions
What is Glutamate?
Major excitatory neurotransmitter in brain
where does glutamate come from?
Comes from metabolic pathway (Krebs cycle) or from glutamine via glutaminase
Glutamate binds to which receptors?
NMDA, kainate, AMPA
AMPA and kainate tend to be grouped together
describe the NMDA receptor for glutamate?
NMDA mediated by glutamate and glycine/serine
NMDA requires membrane depolarization by kainate or AMPA
NMDA involved in memory formation
NMDA Receptors Have Some Unusual Characteristics
What are they?
- In addition to glutamate, another amino acid, either glycine or serine, also needs to be present for receptor activation
- For activation, they not only need to be stimulated by glutamate, they also need to be sufficiently stimulated electrically
- NMDA receptors play a critical role in regulating synaptic plasticity
why is the NMDA considered the coincidence receptor?
because two things need to be present for it in order to be activated
A link between coincidence detection and learning can be seen in associative learning (e.g., Pavlov’s dog).
What is it?
Repeated pairings of the conditioned (CS) and unconditioned (US) stimuli theoretically strengthen the synaptic connections between the CS input neurons and the postsynaptic cells.
This type of learning can be coded in the NMDA receptor
how are kainate and AMPA similar? while NMDA is different?
they tend to be calcium oriented
-important in second order functions
NMDA is sodium oriented
what is GABA?
A universally inhibitory transmitter; found in high concentrations in brain and spinal cord
how is gaba created/processed?
Made from glutamate under control of enzyme glutamic acid decarboxylase (GAD)
Metabolized by GABA-transaminase (GABA-T)
Receptors are GABA(A) and GABA(B) associated with ion channels (they are inhibitory because they allow chloride into cells)
Termination by reuptake with transporters on neuron or glial cell
Excessive glutamatergic signaling is also involved in …
neuronal toxicity, a phenomenon by which nerve cells are damaged.
Too much glutamate can lead to neuronal destruction through overactivity of NMDA receptors, which allows high amounts of calcium ions to enter the neuron.
Excess calcium activates enzymes, which then causes damage to cell structures and to DNA.
difference between GABA (A) and GABA (B)?
GABAA receptors are fast receptors (ionotropic; Chapter 3) and found on the postsynaptic membrane.
GABAB receptors are metabotropic and found on both pre- and postsynaptic membranes.
GAT is the GABA transporter; GAD is glutamic acid decarboxylase, which converts L-glutamic acid to GABA; GABA T is the enzyme that metabolizes GABA.
drugs involved with glutamate vs gaba?
Glutamate:
PCP/ketamine (antagonists)
GABA: (usually sedatives)
Barbiturates, benzodiazepines, alcohol, and antiepileptic drugs (agonists)
what are neurotransmitter Peptides?
Small proteins - chains of amino acid molecules attached in a specific order (ORDERS OF MAGNITUDE LARGER than other transmitters mentioned)
typically made in cell body and transported to presynaptic terminals where they are released.
it makes their supply more finite
Peptide transmitters can be classified into several groups including
the hypothalamic-releasing hormones, the pituitary hormones, and the so-called “gut-brain peptides.”
peptide receptors are ALL…
metatropic
there is no actual ion channel
