Neurochemicals

Question 1

Neurochemistry

Answer 1

• focuses on the basic chemical composition and processes of the nervous system:
  
  • Endogenous (origin inside) chemicals.
  • Everything that produces can affect and be recognized by the body/receptors

Question 2

Neuropharmacology

Answer 2

• is the study of compounds that selectively affect the nervous system:
  
  • Exogenous (origin outside) chemicals.

Question 3

Neurochemistry vs. Neuropharmacology

Answer 3

Neurochemistry focuses on the basic chemical composition and processes of the nervous system, inside

Neuropharmacology is the study of compounds that selectively affect the nervous system, outside

Question 4

Neurochemicals

Answer 4

• substances released by one cell that produces a reaction in a target cell
• Chemical synapses can be directed and non-directed synapses

Question 5

Non-direct

Answer 5

act on more distant neurons

Question 6

Neurotransmitters

Answer 6

directed, a chemical messenger that communicates across a synapse.

• Acts on neurons in its own immediate vicinity
• focused effect
• primary messengers of the action potential

Question 7

Neuromodulators

Answer 7

non-directed, a chemical messenger that communicates with target cells more distant than the synapse by diffusing away from the point of release.

• this process is known as volume transmission because large volumes of the nervous system can be influenced
• remain in the CSF for long periods of time during which they can influence the CNS
• more global general effects

Question 8

Neurotransmitters vs Neuromodulators

Answer 8

Neurotransmitters- directed

Neuromodulators- non-directed

Question 9

Neuromodulation

Answer 9

the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons

Question 10

Neurohormones

Answer 10

a chemical messenger that communicates with target cells at a great distance travelling through the blood supply to reach targets.

Question 11

Neurochemical receptor sites

Answer 11

regardless of the distance traveled these chemical messengers will interact only with other cells that have specialized receptor sites to receive them

Question 12

Three terms to identify a neurochemical

Answer 12

1. The substance must be present within a presynaptic cell
2. The substance is released in response to presynaptic depolarization
3. The substance interacts with specific receptors on a postsynaptic cell

Question 13

Six Criteria for neurotransmitters, expanded

Answer 13

1. Substance exists in presynaptic axon terminals.
2. Synthesized in presynaptic cells.
3. Released when action potentials reach axon terminals.
4. Receptors for the substance exist on postsynaptic membrane.
5. When applied, substance produces changes in postsynaptic potentials.
6. Blocking substance release prevents changes in postsynaptic cell.

Question 14

Types of Neuro Chemicals

Answer 14

1. Small molecules
2. Neuropeptides
3. Gasotransmitters

Question 15

1. Small molecules

Answer 15

• 1- Amino acids
• 2- Amines
• synthesized in the axon terminal
• vesicles recycled
• lower levels of calcium
• deactivated by reuptake

Question 16

Neuropeptides

Answer 16

chains of amino acids, acts as all three neurochemicals

• Synthesized in the cell body and are transported the length of the axon
• Vesicles used once
• Higher levels of calcium which requires more AP’s to reach the axon terminal
• Diffuse away from the synapse or are broken down by enzymes

Question 17

Gasotransmitters

Answer 17

Influence adjacent neurons in similar ways to more classical chemical messengers. A gas such as nitric oxide that performs a signaling function

Question 18

Amino acids

Answer 18

• 8 of them, three are significant
  
  • Glutamate
  • Gamma-aminobutyric acid (GABA)
  • Glycine
• Excited? Inhibited? Either way, we have a neurotransmitter for you

Question 19

Glutamate and Glycine vs GABA

Answer 19

• Glutamate and glycine are among the amino acids used to build other proteins, GABA is not

Question 20

Glutamate

Answer 20

• is the most common excitatory neurochemical in the CNS
• Is synthesized from a-ketoglutarate in the mitochondria
• Once released glutamate is taken up by neurons and astrocytes since the synaptic area must be cleaned of excess glutamate because extended action of glutamate on neurons can be toxic

Question 21

Glutamate and the brain

Answer 21

• MSG has glutamate inside it which causes chest pain headache nausea and rapid heartbeat
• the BBB prevents dietary glutamate from entering the brain

Question 22

Glutamate receptors

Answer 22

• Glutamate receptors can be ionotropic or metabotropic

Question 23

Glutamate receptors process (AMPA AND NMDA)

Answer 23

1. both voltage and lita-gated dependent glutamate receptors which means they will not open unless glutamate is present, and the postsynaptic membrane is depolarized at the same time.
2. Low-level Glutamate release activates AMPA receptor
3. NMDA receptors are found nearby, but are not activated by low levels of glutamate since they are blocked by magnesium ions
4. Once we get many action potentials, this causes a greater stimulation of AMPA receptors which will cause the postsynaptic neuron to depolarize which causes the magnesium blockage on the NMDA cell to be removed allowing it to open in response to the binding of glutamate
5. This allows calcium ions to move through the NMDA receptor
6. The more calcium ions, the more AMPA receptors, which is more responsive to glutamate. This allows more positive ions (sodium and calcium) to enter the cell, further depolarizing it
7. Once calcium gets to cell nucleus it will make transcription for more AMPA receptors because that is what allows the depolarization to happen.
8. Since there are more receptors that respond to glutamate, it is more sensitive to glutamate.
9. With calcium, NMDA receptor participates in functions like memory
10. Calcium is also responsible for the excess glutamate

Question 24

Where do we have glutamate?

Answer 24

• We have glutamate in all cells in all of the neurons since AA is building block of protein.

Question 25

How do Glutamatergic transport?

Answer 25

* Only Glutamatergic neurons have transporters that pack the glutamate into synaptic vesicles

Question 26

GABA

Answer 26

* Serve as the major inhibitory neurochemical of the CNS (amino acids) * synthesized from glutamate through the action of the enzyme glutamic acid * Glutamate + enzyme= GABA * there are two types of GABA receptors, GABA a and GABA b

Question 27

GABA A

Answer 27

* Ionotropic (fast) postsynaptic chloride channels which allow negatively charged chloride ions into the cell causing hyperpolarization * This binding opens up an ion channel * Produces IPSP: * Let something negative in * Let something positive out

Question 28

GABA B

Answer 28

Metabotropic (slow) inhibitory, potassium cell channels which allow positively charged potassium ions to leave the cell * Example: by opening K⁺ *exit* channels, causing hyperpolarization.

Question 30

Glycine

Answer 30

* Acts directly as an inhibitory neurochemical mainly in synapses formed by spinal cord interneurons but also in smaller numbers elsewhere in the nervous system * Excitatory role with glutamate at the NMDA receptor * removed by reuptake * Ionotropic glycine receptors allow chloride into the cell which leads to hyperpolarization * receptors are blocked by poison straightening which kills by preventing the diaphragm muscles from relaxing * participates in the management of sleep waking cycles

Question 31

* **Glutamate docking to the receptor _sub-unit_** causes what?

Answer 31

* **changes its shape by forming chemical bonds.** * **This opens the channel of which it is part.** * THIS ALL TO SHOW US THAT THE TYPE OF RECEPTOR MATTERS, IF THIS WAS GABA IT WOULDN’T BE ACCEPTED

Question 32

AMPA and NMDA are basis of

Answer 32

learning and memory.

Question 33

Calcium triggers and transformation of..

Answer 33

* DNA to RNA to protein.

Question 34

NMDA receptors are activated only by an

Answer 34

* ***effective stimulus*** *–* strong enough to cause depolarization. * NMDA receptors let in Ca⁺⁺ ions – which start processes that **add** more AMPA-type **glutamate receptors** to the post-synaptic membrane.

Question 35

How are NMPA receptors made? What is this concept called?

Answer 35

This is essence of life. First time you see it this happen but eh. Again. Again. Again. Each time you make more ampra receptors. You make AMPA receptors: * **Hebbian learning** (named after Donald Hebb, the Canadian psychologist who proposed the theory): * ***“Neurons that fire together, wire together”.*** * * **Plasticity** – more receptors means more effectiveness.

Question 36

Excitotoxicity

Answer 36

* neural injury such as stroke may cause excess release of glutamate, which is toxic to neurons.

Question 37

Clearance after action:

Answer 37

Astrocytes (glia) are involved in the uptake of glutamate from the synapses.

Question 38

Why would we want to inhibit neural activity?

Answer 38

* Sharpening focus of perceptions – filtering noise by lateral inhibition. * Synchronization of firing. * Preventing Epilepsy.

Question 39

Drugs and Alcohol

Answer 39

* **Noncompetitive ligands** bind to a modulatory site on the receptor. * The substances pictured are **noncompetitive GABA agonists**. * *Benzodiazepines* (Valium): affect frequency of channel opening. * *Barbiturates:* affect duration of channel opening * GABA receptors are same as alchahol/drugs (see pic on slide 31). Gaba binds to iontopic but we have other sites that can modulate GABA like valium^.

Question 40

GABA clearance

Answer 40

is cleared from the synapse by transporters and by glia, and metabolized into components by GABA transaminase.