Introduction to CNS - Kelly 2 Flashcards Preview

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Flashcards in Introduction to CNS - Kelly 2 Deck (47)
1

Blood brain barrier

Isolates CNS
Modified endothelial cells with light junctions: lipophilic things can pass, but ionic charged substances can't
Lack of leakage
Astroglial process and pericytes
Highly lipophilic
BBB can be affected during injury or infection

2

Neuronal systems involved in

Cognitive processing
Memory
Emotional processing
Sensory processing
Motor processing
Autonomic Processing

3

CNS neurotransmission

Depolarization at nerve terminal
Ca enters through channels
Promotes fusion of vesicles with nerve terminal to allow release
NT can be taken back or degraded

4

Sensitization of receptors

Sustained reduction in NT release or long term use of antagonist
Sensitized response when antagonist is taken away
Up regulation

5

Desensitization

Sustained blockade of NT reuptake or long term use of agonist
Receptor down-regulation: internalized

6

Important CNS receptors

Voltage gates
Ligand-gated ion channels
Membrane delimited metabotropic ion channel
Diffusible second messager metabotropic ion channel

7

Voltage gages ion channel

Ions moved based on what is favourable for voltage of cell
Pore is lined with charged amino acids
Voltage affects aa and they move to expose different areas
Facilitate opening that certain ions can move through

8

Ligand-gated ion channel

Inotropic channel
Channel is gated by binding of one, two or more ligands

9

Diffuse second messager metabotropic ion channel

Diffusible messenger activated ion channel

10

Excitatory membrane potential

Reaching AP
Conducted along axons and evoke NT release from nerve terminal
If enough EPSPs, AP will happen

11

Inhibitory membrane potential

Usually hyper polarizes the cell membrane and inhibits AP formation and can decrease NT release

12

Long tract cellular organization

Messages over long distances
Motor control
Relay, projection neurons

13

Local circuit cellular organization

Short, modulation
Shape recognition in the optic tract
Interneurons

14

Divergent

Widely projecting neurons
Global functioning
Sleep-wake cycles
Diffuse system

15

CNS neurotransmitters

Amino acids
Acetylcholine
Monoamines
Peptides
Endocannabinoids

16

Criteria for a NT

Must be present in a higher concentration in the synapse than in other areas (localized)
Released by electrical or chemical stimulation via Ca-dependent mechanism
Produce a post-synaptic response similar to nerve stimulation (synaptic mimicry)
Mechanism for termination of transmitter action

17

Amino acids

High concentration in the CNS
Potent
Excitatory: glutamate
Inhibitory: GABA, glycine

18

Glutaminase

Converts glutamine to glutamate

19

Glutamate decarboxylase

Converts glutamate to GABA

20

Glutamate

Major excitatory NT in CNS
Inotropic and metabotropic receptors
Termination by glia uptake, where it is converted to glutamine

21

Inotropic glutamate receptors

NMDAR, AMPAR, KAR

22

Metabotropic glutamate receptors

mGLUR1
Postsynaptic (Gq) and presynaptic (Gi)

23

NMDAR

Very calcium permeable when open
Reenforcement of Ca circuit
Do not like to be opened, at rest blocked by Mg
Need huge depolarization to be activated (summation)
Glu opens AMPAR non-selective ion channels which allows for further depolarization and dissociation of Mg

24

GABA

Inhibitory
Inotropic (GABAA, Cl) and metabotropic (GABAB, Gq)
Widely expressed
GABAB can be presynaptic
Ligand gated ion channel, binds between 2 subunits of pentameric structure
Allosteric modulators need orthosteric activity
Direct activation of K channel

25

Glycine

Inhibitory
Inotropic (Cl)
Limited expression: interneurons in SC and brainstem

26

Acetylcholine

Ionotopic (nicotinic)
Metabotropic (muscarinic)
Excitatory, inhibitory
Widely expressed
Cognitive functions
Target in treatment of Alzheimers disease

27

Aceyltransferase

Convers AcCoA to acetyl choline

28

Muscarinic receptors

M1, M3, M5: Gq, increase IP3, DAG, decrease cAMP, gK
M2, M4: ion channel, increase gCa, gK, GNa

29

Monoamines

Dopamine, norepinephrine, serotonin (5-HT)
Derived form aa
Synthesis enzyme/neuron dependent
Small amounts
Complex functions: alertness, consciousness

30

Dopamine

5 known receptors
D1 or D2
Metabotropic
Inhibitory
Diffuse
Target in Parkinson's disease
L-Tyrosine to DOPA to dopamine
Behaviour, drug reenforcement, emesis, hormone release, mood, motor coordination, olfaction

31

Tyrosine hydroxylase

Converts L-tyrosine to DOPA

32

L-amino acid decarboxylase

Converts DOPA to dopamine

33

D1, D5

Excitatory
Gs, Gq
Increase cAMP, IP3, DAG, Ca

34

D2, D3, D4

Inhibitory
Gi/o
Decrease cAMP, K, VDCC

35

Norepinephrine

Adrenergic receptors alpha and beta: metabotropic
Excitatory
Diffuse
Attention, arousal
Dopamine converted into norepinephrine by dopamine P hydroxyase
Anxiety, learning, memory, mood, sensory, processing, sleep

36

Dopamine P hydroxylase

Converts dopamine to norepinephrine

37

A1 receptor (NE)

Gq
Increase IP3, DAG, Ca

38

A2 R (NE)

Gi
Decrease cAMP

39

B1, B2 (NE)

Gs
Increase cAMP

40

Serotonin

15 5-HT receptors (metabotropic) except 5-HT3 which is inotropic
Tend to be inhibitory
Diffuse
Sleep, temperature, appetite, neuroendocrine control
Target in treatment of affective disorders

41

Tryptophan hydroxylase

Converts tryptophan to 5-hyroxytryptophan, which is converted to 5-hydroxytryptoamine by LAAD

42

Neuropeptides

Many
Opioids (endorphins, enkephalins)
Pain sensation
Target of analgesics, drugs of abuse
Metabotropic
Can be released in conjunction with other NTs
Differ from non-peptide transmitters:
1. Synthesized in cell body and transported to nerve ending
2. No reuptake or enzyme degradation

43

Endocannabinoids

Rapidly synthesized and not stored
Act on presynaptic receptors
Cannabinoid receptor 1
Suppress NT release
Memory, cognition, pain perception

44

Endocannabinoid signalling

Retrograde messaging
Synthesized by Ca depended enzymes and released from postsynaptic neurons
Signal travels retrogradely across synapse acting CB1R on presynaptic nerve terminal, inhibiting Ca channels
Results in suppression of NT release

45

NO

Gas formed from arginine by NO synthase in CNS neurons
May participate in retrograde NT and LTP

46

Leptin/Orexin

Hormone modulators formed in hypothalamus
Important in regulation of appetite

47

Purines

Adenosine and ATP
activate specific purinergic receptors: evidence that ATP is a cotransmitter