T6

Question 1

Synapses are …

Answer 1

Synapses are functional contacts between neurons.

Question 2

Diversity of synaptic locations (general)

Answer 2

In the nervous system there are a diversity of synapses, with different location, structure, function, and target.

Synapses can deliver transmitters to the dendrites, cell body, or axon of a neuro and transmitters can control the actions of the neuron in different ways.

Question 3

Diversity of synaptic locations (according to membrane differentiations)

Answer 3

Gray I type: (asymmetrical) the differentiation in the postsynaptic membrane is higher than in the presynaptic. Neurotransmitter: usually excitatory

Gray type II: (symmetrical) differentiation in pre and postsynaptic membrane are similar. Neurotransmitter: usually inhibitory.

Question 4

Types of synapses (general)

Answer 4

The majority are axodendritic, or axo-somatic and dendrites axon-axon are rare (pres synaptic inhibition). (check image)

Question 5

Types of synapses (chemical)

Answer 5

is the process of neurotransmission where messenger molecules are released from one neuron to excite the next neuron.

The presynaptic membrane forms the axon terminal, the postsynaptic membrane forms the dendritic spine, and the space between the two is the synaptic cleft.
- Specialised contact without direct cytoplasmatic connection between the nerve cells
- The transmission between cells is with a chemical. Neurotransmitter
- The upstream cell releases a neurotransmitter
- The neurotransmitter gets in contact with the post cell and the ion channels are activated and induce an action potential

Question 6

Types of synapses (electrical)

Answer 6

is the process that some neurons influence each other electrically through a gap junction. Some neurons influence each other through a gap junction, where the prejunctional and postjunctional cell membranes are fused.

Neurons are Isopotentialand bidirectional

Typical of invertebrates:
- Specialised contact with a direct cytoplasmatic connection between the two cells
- The electric flow induces an electric current between the two cells and there are changes in the tension.
- The electric synapses are permeable to uncharged parts that they are till 100Da

Glucose, second messenger

Question 7

Chemical synapses (parts)

Answer 7

Presynaptic structure: terminal axon

Synaptic cleft: extracellular proteins and chemicals to help join the membranes

Postsynaptic structure: dendrites

Question 8

Chemical synapses (membrane differentiations)

Answer 8

Active zones: presynaptic membrane, proteins with pyramidal shape

Postsynaptic density: contains the NT receptors in the axon terminal there are specialized structures:
- Mitochondria: the organelles that supply the cell’s energy needs
- Storage granules: large compartments that hold several synaptic vesicles.
- Microtubules that transport substances, including the neurotransmitter, to the terminal.

The synapse is sandwiched by many surrounding structures including glial cells, other axons and dendritic processes, and other synapses.

Question 9

Chemical synapsid (step 1)

Answer 9

Step 1: neurotransmitter synthesis and storage (some neurotransmitters are transported rom the cell nucleus to the terminal button. Others, made form building blocks are imported into the terminal, are packaged into vesicles there.)

Derived from chemical precursors (food, glial cells…)

Protein synthesis from DNA Regardless of the origin NT can be found in:
1. Warehouse in granules
2. Attached to the microfilaments
3. Attached to the presynaptic membrane

NT are carried out in vesicles that joins the cell membrane and release the NT in to the cleft space.

Question 10

Chemical synapses (step 2)

Answer 10

Step 2: neurotransmitter release (in response to an action potential, the transmitter is released across the membrane by exocytosis.)
- EXOCYTOSIS
- Action potential open the Ca2+ voltage channels
- Ca2+ entrance binds to Calmodulin
- Calmodulin helps to bind vesicle with the cell membrane
- Snare proteins: Snare-v, Snare-t

Question 11

Chemical synapses (step 3)

Answer 11

Step 3: receptor-site activation (the transmitter crosses the synaptic cleft and binds to a receptor)

The transmitter may:
1. Depolarize the postsynaptic membrane →excitatory action
2. Hyperpolarize the postsynaptic membrane →inhibitory action

Initiate other chemical reactions(cascade) that may inhibit or excitate the postsynaptic cell How much NT is needed to generate postsynaptic AP? →Quantum: the content of 1 single vesicle. The number of quantum depend on:
1. The amount of Ca2+
2. The number of waiting vesicles

Question 12

Chemical synapse (step 4)

Answer 12

Step 4: neurotransmitter deactivation (the transmitter is either taken back into the terminal or inactivated in the synaptic cleft).
The neurotransmitter is removed from receptor sites in at least four ways:
1. Diffusion: Some of the neurotransmitter simply diffuses away from the synaptic cleft and is no longer available to bind to receptors.
2. Degradation by enzymes in the synaptic cleft.
3. Reuptake: Membrane transporter proteins specific to that transmitter may bring the transmitter back into the presynaptic axon terminal for subsequent reuse. The by -products of degradation by enzymes also may be taken back into the terminal to be used again in the cell.
4. Glial uptake: Some neurotransmitters are taken up by neighbouring glial cells. Potentially, the glial cells can also store transmitters for re -export to the axon terminal. If the terminal is very active, the amount of NT made and stored increases. If the terminal is not often used, local enzymes break down excess transmitter

Question 13

Electrical synapsis (general 1)

Answer 13

Electrical synapses are usually bidirectional and are faster than chemical synapses.
Ion channels in one cell membrane connect to ion channels in the other membrane, forming a pore that allows ions to pass directly from one neuron to the next.

Gap junctions: 6 connexines → connexon →Gap junctions

Question 14

Electrical synapsis (characteristics)

Answer 14

Easy structure
Direct transmission
Gap junctions
All ions can pass through
Typical of invertebrates: escape mechanisms
High synchronized neurons
Present in other cells like glial cells, epithelial cells
Brain development

Question 15

Electrical synapsis (general 2)

Answer 15

1 mV →Not enough to generate AP but with synaptic integration can generate AP
They are a minority, electrical synapses are found in all nervous systems, including the human brain.
The membranes of the two communicating neurons come extremely close at the synapse and are linked together by an intercellular specialization called a gap junction.
Gap junctions contain precisely aligned, paired channels in the membrane of the pre- and postsynaptic neurons, such that each channel pair forms a pore
As a result, substances can simply diffuse between the cytoplasm of the pre- and postsynaptic neurons.
In addition to ions, substances that diffuse through gap junction pores include molecules with molecular weights as great as several hundred daltons. This permits ATP and other important intracellular metabolites, such as second messengers.

Question 16

neurotransmiters

Answer 16

There are more than 100 neurotransmitters, belonging to five groups: acetylcholine, biogenic amines, amino acids, neuropeptides, and gases. A single neurotransmitter may have more than a dozen different receptors.

Question 17

A molecule is considered a neurotransmitter:

Answer 17

Must be synthesized and stored in the presynaptic neuron.

Must be released in the synaptic cleft upon stimulation.

Must carry a message to the postsynaptic cell by:
- Influencing the voltage of the postsynaptic membrane.
- Changing the structure of the synapse.
- Transmitting from post-to presynaptic (retrograde signalling)

Question 18

neurotransmitters (frog)

Answer 18

Otto Loewi (Nobel prize 1936) connected a frog’s heart, with the nerves that stimulated it still attached to a small glass container filled with ringer solution. Stimulated the nerve fibres electrically, noted how the number and strength of the heart beats depended on, the stimulation of the individual sympathetic (speed) and parasympathetic (slow) nerve fibres. He then transferred the fluid which had been pumped out of the heart into another heart. The fluid itself was able to change the activity of the heart, as if it had taken on the properties of stimulating the nerve fibres. Simple experiment showed that the nerve fibres had released substances into the fluid which had an effect on the organ.

Question 19

Each NT has its specific chemical structure.

Answer 19

Most of the known NTs are either:
amino acids
Amines
peptides.

Question 20

Based on their structure, synthesis (production), functions and receptors, NTs can be classified as:

Answer 20

Small-molecule NTs
Peptide transmitters
Transmitter gases

Question 21

Achetylcholine Cholinergic neurons (small molecule nt)

Answer 21

The main NT at the muscular junction.
Present at the junction of neurons and muscles, including the heart as well as the CNS (all motor neurons in the brain stem and spinal cord).

Question 22

Achetylcholine Cholinergic neurons are mad eout of 2 substances:

Answer 22

Choline: it is among the breakdown products of fats in foods. The neuron takes it from the extracellular space near terminal buttons.

Acetyl coenzyme (AcetilCoA): comes from the glycolysis (glucose decomposition).

Question 23

Enzymes that synthesize Ach:

Answer 23

AcetylCoA carries acetate to the synthesis locus.
Then cholineacetyltransferase(ChAT) transfers acetatetocholine to form ACh.

Question 24

Enzymes that degrade ACh:

Answer 24

Acetilcolynesterase(AChE) is responsable for Achdegradation in the extracellular space.

AChE blockage leads to decrease heart rate and blood pressure.

Question 25

Acetylcholine (ACH) Cholinergicneurons
Nicotinic Ach receptor: ionotropic(excitatory)

Answer 25

N1 (2α, β, δ): peripheral or muscle subtype (skeleton muscle)
N2: central or neural subtype (autonomic ganglia)
Also present in the cerebral cortex, hippocampus, thalamus, and amygdala; and thus, involved in memory, learning, emotion, and reward processing.

Question 26

Acetylcholine (ACH) Cholinergicneurons
Muscarinic Ach receptor: metabotropic (excitatory and inhibitory)

Answer 26

M1, M3. M5: present at smooth muscle and striatum (excitatory)
M2, M4: diffuse location (inhibitory)
They exert an inhibitory effect over DA neurons in the striatum.

Question 27

Glutamate (Glu) (amino acidergic neurons)

Answer 27

It is synthesized from glucose and other precursors. It is the most important NT in normal brain function, nearly all excitatory neurons in the CNS are glutamatergic.

Question 28

Glutamaergic receptors

Answer 28

• Ionotropic (excitatory)
• AMPA, NMDA, and kainite.
• AMPA and NMDA receptors mediate fast EPSP in the brain.
• NMDA receptors are permeable to Ca2+ →can cause lasting synaptic effects (learning effects via long-term potentiation). Its blockage impairs memory and cognition.
• Metabotropic (excitatory or inhibitory)
• mGluI, II, R1,…,R8

Question 29

Gamma amino-butiricacid (GABA) (amino acidergic neurons)

Answer 29

Glutamate is the precursor of GABA.
GABA is the main inhibitory NT in the CNS.
There are two main types of GABA receptors in the nervous system, each with different mechanisms of action:

Question 30

GABA-A Receptors:

Answer 30

Type: Ionotropic receptor (ligand-gated ion channel).
Action: When GABA binds to these receptors, it opens a channel that allows chloride ions (Cl⁻) to flow into the neuron.
This influx of negatively charged ions makes the neuron less likely to fire, leading to inhibition.
Widely distributed throughout the central nervous system.
Function: These receptors mediate fast inhibitory synaptic transmission and are responsible for quick inhibitory effects in the brain.
Clinical Importance: Many drugs, including benzodiazepines, barbiturates, and alcohol, act on GABA-A receptors, enhancing their inhibitory effects, which can lead to sedation, muscle relaxation, and anticonvulsant properties.
Location: Primarily found in the retina.
Function: They play a role in visual processing.

Question 31

GABA-B Receptors:

Answer 31

Type: Metabotropic receptor (G-protein coupled receptor).
Action: When GABA binds to GABA-B receptors, it activates G-proteins, which in turn open potassium (K⁺) channels and close calcium (Ca²⁺) channels. This hyperpolarizes the neuron, reducing its excitability.
Location: Found in the brain and spinal cord.
Function: GABA-B receptors mediate slower, longer-lasting inhibitory effects compared to GABA-A receptors. They are involved in regulating muscle tone and modulating neurotransmitter release.
Clinical Importance: GABA-B agonists, such as baclofen, are used to treat conditions like muscle spasticity and certain types of epilepsy.

Question 32

GABA-C Receptors (Now considered a subset of GABA-A receptors):

Answer 32

Type: Ionotropic receptor.
Action: Like GABA-A receptors, they also open chloride ion channels upon GABA binding but have different subunit compositions and slower kinetics.

Question 33

example, where are GABAergin neurons located?

Answer 33

GABAergic neurons (neurons that release GABA, the primary inhibitory neurotransmitter in the brain) are widely distributed throughout the central nervous system. Here are key regions where they are located:
- cerebral cortex, basal ganglia, hippocampus, thalamus, cerebellum, spinal cord, hypothalamus and retina

Question 34

Cerebral cortex (GABAergin neurons)

Answer 34

Cerebral Cortex:
Location: Found in different layers of the cortex.
Function: GABAergic interneurons play a role in regulating the excitatory activity of glutamatergic neurons, which are involved in higher-order functions like cognition, sensory perception, and motor control. They help maintain a balance between excitation and inhibition in cortical circuits.

Question 35

Basal ganglia (GABAergin neurons)

Answer 35

Basal Ganglia:
Location: Includes areas such as the striatum (caudate nucleus and putamen), globus pallidus, and substantia nigra.
Function: GABAergic neurons are critical for controlling voluntary movements. In the basal ganglia, they regulate motor output and are involved in movement disorders like Parkinson’s and Huntington’s disease.

Question 36

Hippocampus (GABAergin neurons)

Answer 36

Hippocampus:
Location: Found throughout the hippocampal formation.
Function: GABAergic interneurons regulate excitatory inputs in the hippocampus, which is important for learning and memory. These neurons help maintain the balance needed for synaptic plasticity.

Question 37

Thalamus (GABAergin neurons)

Answer 37

Thalamus:
Location: Certain nuclei in the thalamus, like the reticular nucleus, consist primarily of GABAergic neurons.
Function: GABAergic neurons in the thalamus help regulate the flow of sensory and motor information to the cortex, and they are involved in sleep-wake cycles.

Question 38

Cerebellum (GABAergin neurons)

Answer 38

Cerebellum:
Location: Primarily in Purkinje cells, which are GABAergic neurons located in the cerebellar cortex.
Function: These neurons play a crucial role in motor coordination and fine-tuning movements by inhibiting the output of the cerebellum to other motor areas.

Question 39

Spinal cord (GABAergin neurons)

Answer 39

Spinal Cord:
Location: GABAergic neurons are found in different layers of the spinal cord, particularly in the dorsal horn.
Function: They play an essential role in processing sensory input, especially pain, and in modulating motor reflexes.

Question 40

Hyphotalamus (GABAergin neurons)

Answer 40

Hypothalamus:
Location: Certain areas of the hypothalamus contain GABAergic neurons, such as the ventrolateral preoptic nucleus.
Function: These neurons are involved in regulating sleep, feeding behaviors, and hormonal control.

Question 41

Retina (GABAergin neurons)

Answer 41

Retina:
Location: In the inner nuclear layer and ganglion cell layer of the retina.
Function: GABAergic neurons in the retina help process visual information by regulating the activity of other neurons involved in transmitting signals to the brain.

Question 42

Glycine (Gly) (amino acidergic neurons)

Answer 42

Glycine receptors (GlyRs) are inhibitory receptors in the central nervous system, particularly prominent in the spinal cord, brainstem, and retina. Glycine is the primary inhibitory neurotransmitter in these regions, similar to how GABA functions in other areas of the brain.

Question 43

Glycine Structure and Function:

Answer 43

Type: Ionotropic receptor (ligand-gated ion channel).

Action: When glycine binds to the GlyR, the receptor opens a channel that allows chloride ions (Cl⁻) to flow into the neuron. This causes hyperpolarization (makes the inside of the neuron more negative), reducing the likelihood that the neuron will fire, thus inhibiting neural activity.

Location:
Spinal cord and brainstem: GlyRs are critical for controlling motor and sensory pathways.
Retina: Involved in visual processing.
Other parts of the brain: Present but less prevalent than in the spinal cord and brainstem.

Question 44

Catecholamines (amino acidergic neurons)

Answer 44

Their precursor is tyrosine. There is a biochemical sequence that synthesizes these amines in succession. The action of catecholamines is terminated by selective uptake, not by degradation.

Question 45

Dopamine(DA) (amino acidergic neurons)
+ structure and functions

Answer 45

Structure and function:
DA (and all catecholamines) is derived from tyrosine.
It abounds in the striatum and substantia nigra and has projections to frontal cortical regions.
DA is involved in movement control, mood regulation and attention.
Tyrosine is converted to a compound named “dopa”, which is then converted into DA.
The action of DA is terminated by selective uptake of remaining DA in the synaptic cleft.

Question 46

Dopamine (amino acidergic neurons) (synthesis and degradation)

Answer 46

Synthesis and degradation:
Tyrosine is converted to a compound named “dopa”, which is then converted into DA.
The action of DA is terminated by selective uptake of remaining DA in the synaptic cleft.

Question 47

Norepinephrine(NE) (amino acidergic neuron)

Answer 47

NE is derived from DA.
NE originates in the locus coeruleus.
It can act as a NT and a hormone (when released from the adrenal glands into the bloodstream).
It often called the “stress hormone” as it is used by the sympathetic system (a branch of the autonomic nervous system, ANS) to prepare the body for a fight-or-flight response, increase heart rate and blood flow.
It is also involved in the regulation of sleep-wake cycles and feeding.

Question 48

Epinephrine (adrenaline) (amino acidergic neuron)

Answer 48

It is the last in the chain of catecholaminergic neurons; it derives from NE.
It can act as a NT and a hormone.
It is important for ANS function similar to NE; it produces a coordinated, body-wide set of sympathetic effects (“rush of adrenaline”).
Unlike NE, epinephrine is only released during stressful situations (fight-or-flight response) and has more diffuse effects than NE.

Question 49

Serotonine(5-HT) (other amino NT)

Answer 49

Structure and function:
5-HT is derived from tryptophan, an essential amino acid that is present in food (e.g., grains, meat, dairy products and chocolate).
Serotoninergic neurons are few in number but abundant in the raphe nuclei located in the brain stem.
Regulates mood, emotional behaviour, and sleep.

Synthesis and degradation:
Tryptophan is converted into 5-HTP and then to 5-HT.
At the axon terminal, 5-HT is either reloaded via synaptic vesicles or degraded by monoamine oxidase (MAO).

Question 50

Histamine (other amino NT)

Answer 50

Histaminergic neurons extend throughout the CNS from the hypothalamus.
Associated with the immune reactions such as allergic responses after exposure to a foreign substance (e.g., mosquito venom), mast cells led to histamine release swelling and redness at the site of injury.
Antihistamines reduce pain, swelling, and itching by blocking histamine receptors.

Question 51

Peptide transmitters or neuropeptides (other amino NT)

Answer 51

Substance P:
Present in the cortex, hippocampus, spinal cord, and gastrointestinal tract.
Associated with inflammatory processes and pain (nociception).

Opioids:
Include endorphins, enkephalins or dynorphins.
All bind to metabotropic receptors that are sensitive to opium.
Endorphins modulate nociceptive information and mediate placebo effects(Zubieta et al., 2005).
Synthetic opioids (e.g., morphine, heroin) mimic the actions of these neuropeptides →pain relief, euphoria, depressed breathing and constipation.

Question 52

Adenosinetriphosphate(ATP)
(unconventional NT)

Answer 52

ATP (adenosine triphosphate) can act as a neurotransmitter.
Although ATP is primarily known as the energy currency of the cell it also functions as a signaling molecule in the nervous system.
ATP is released by neurons and acts on specific receptors called purinergic receptors (P2 receptors), which are involved in various processes.
Neurotransmission: ATP is co-released with other neurotransmitters (like acetylcholine or norepinephrine) and can modulate synaptic activity.
Pain signalling: ATP plays a role in nociception (the sensory perception of pain.)
Glial cell communication: ATP acts as a signaling molecule between neurons and glial cells, playing a role in neuroinflammation and the regulation of neuronal activity.
After ATP acts as a neurotransmitter, it is rapidly broken down into adenosine, which also functions as a neuromodulator, primarily having inhibitory effects on neuronal activity.

Question 53

Endocanabinoids (unconventional NT)

Answer 53

They are retrograde messengers (communicate from post to pre): are released by postsynaptic neurons and act on presynaptic neurons.
High firing in the postsynaptic neuron stimulates endocannabinoid synthesis.
Peculiar qualities (1) produced on demand, (2) small and permeable (rapid diffusion), and (3) selectively bind to CB1 receptors.
Have an important role in maintaining body homeostasis (brain, endocrine and immune function).
Endocannabinoids and marijuana (cannabis) are closely related because the active compounds in marijuana, known as cannabinoids, interact with the same system in the body as endocannabinoids—the endocannabinoid system (ECS).

Question 54

Transmittergases (unconventional NT)

Answer 54

Evidence for gasotransmitter functions is still sparse.
Nitric oxide (NO), synthesized from the amino acid arginine, works as a retrograde messenger that acts and breaks down very rapidly regulation of blood flow and control of smooth muscle relaxation (gastrointestinal tract).
Other potential gaseous NTs are carbon monoxide (CO) and hydrogen sulphide(H2S).

Question 55

Summary (what NT are, types, examples, function)

Answer 55

Neurotransmitters are chemical messengers in the nervous system.
Types:
Excitatory (e.g., Glutamate) – Stimulate neuron activity.
Inhibitory (e.g., GABA) – Reduce neuron activity.
Modulatory (e.g., Dopamine, Serotonin) – Regulate multiple functions.
Examples:
Dopamine: Motivation, pleasure, reward.
Serotonin: Mood, sleep, appetite.
Acetylcholine: Muscle movement, memory.
Endocannabinoids: Regulate pain, mood, appetite.
Function: Transfer signals between neurons to maintain brain and body functions.