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Neurology > Neurotransmitters > Flashcards

Neurotransmitters Flashcards

1
Q

What are the 4 main neurotransmitter classes

A

Amino acids

Biogenic amines

Purines

Neuropeptides

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2
Q

How are neurons classified from a neurotransmitter view point?

A

The predominant neurotransmitter they synthesize and releases when firing
- all neurons release different types of neurotransmitter sand have various receptors, but the predominant one is how the neuron is labeled

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3
Q

Two main type of neurotransmitter receptors

A

1) ion channels
- known also as inotropic receptors
- very rapid intracellular changes

2) G-protein coupled receptors (GPCRs)
- known also as metabotropic receptors
- effects lasts tens of seconds -> minutes
- activated G-Protein propagates cAMP/calcium production -> desired cell response

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4
Q

Excitatory vs inhibitory receptor actions

A

Excitatory

  • depolarize membranes of neurons (becomes more positive by influx of Ca+2 and/or NA+)
  • excitatory ionotropic receptors generate EPSP which helps simplify action potential depolarization

Inhibitor

  • hyperpolarize membranes
  • inhibitory ionotropic receptors generate IPSPs which antagonizes action potentials

metabotropic receptors on neurons contribute by setting overall tone of the neuron (prime it to be easy or harder for it to fire. DOES NOT actually generate the action potential or inhibit the action potential

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5
Q

Metabotropic signaling G-protein specifics

A

G(as) protein activation stimulates cAMP production

G(aio) protein activation inhibits cAMP production

G(aq) protein stimulates Phospholipase C (PLC)

An increase in PLC is directly correlated with increases in DAG and IP3
- resulting signal is intracellular increases in calcium and subsequent downstream signaling

An increase in cAMP is directly correlated with an increase in Protein Kinase A (PKA)
- resulting signal is phosphorylation of a protein target (activates)

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6
Q

What does the protein calmodulin do?

A

Acts as a protein activator in response to elevated calcium levels
- phosphorylated downstream proteins in a signal

ONLY activated in response to increased calcium

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7
Q

Secondary effects of GPCR kinase activity

A

Changes in gene transcription

Receptor desensitization

Receptor sensitization

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8
Q

Receptor desensitization mechanism

A

1st dose
- receptors are internalized and either recycled or degraded via phosphorylation to attempt to prevent OD or ADRs

2nd dose
- Fewer receptors are present on cell surface = less amplitude in response

a refractory period is required for “receptor recovery” (reversal of sensitization), hence if giving two doses with a small time frame, the second has less of an effect

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9
Q

Receptor sensatization mechanisms

A

usually only occurs in the chronic presence of an antagonist

Neuron responds by upregulating target receptor (survival mechanisms)

Sudden absence of the antagonists after upregulation causes increased apparent does and elevated response to drugs that were being antagonized

applies to both ionotropic and metabotropic receptors

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10
Q

Hierarchical vs diffuse pathways of neurotransmitters

A

both are movement of action potentials through neurons or series of neurons

Hierarchical
- signal moves down 1 by 1 neuron

Diffuse
- signal moves across an area at once, not 1 by 1

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11
Q

Tracts vs circuits

A

Tracts
- anatomical structures/bundles of neuronal axons

Circuits
- group of neurons that interact with each other to modulate a specific set of organism functions

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12
Q

Hierarchical neurotransmitter specifics

A

Glutamate, GABA and glycine all work in this way

Neurotransmitters that use this method of propagation function to control the following

  • sensory perception
  • motor control
  • some cognitive functions

Use myelinated long axons

Possess local circuit neurons (interneurons) that tune and regulate signals (allow it to propagate at the correct speed and stay on the hierarchical pathway)

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13
Q

Diffuse neurotransmitter specifics

A

Dopamine, NE, serotonin, histamine, Orexin and ACh all work this way

Neuro transmitters that use this pathway function closely for global body functions and changes (ex: sympathetic response throughout the body)

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14
Q

Where are dopamine cell bodies found?

A

Ventral regimental area and substantia Nigra in the Brain

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15
Q

Where are NE cell bodies found?

A

Locus coeruleus in the brain

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16
Q

Where are serotonin cell bodies found?

A

Raphe nuclei in the brain

17
Q

Where are ACh cell bodies found?

A

Nucleus Basalis of Meynert in the brain

Cholinergic brain stem nuclei

Diagonal band of Broca

Medial septal nucleus

18
Q

Glutamate neurotransmitter specifics

A

Present in 90% of excitatory synapses

Possess 5 metabotropic glutamine receptors all of which are coupled to either G(aq) of G(aio) proteins

Have three ionotropic receptors as well

  • AMPAR
  • Kainate
  • NMDAR
19
Q

Difference between AMPA and NMDA receptors for glutamate

A

AMPA: “solo receptor”

  • permeable to (NA+/K+) only
  • open super quickly and desensitize quickly
  • level of AMPA receptors is directly correlated to sensitivity on a neuron

NMDA: “coincidence detector”

  • permeable to (NA+/K+ and Ca2+)
  • open slower and desensitize slower
  • requires glycine (coagonist) to open
  • possess zinc and magnesium bindings sites on Channel pores
  • only open after AMPA receptors have been de polarized (since mag. Doesn’t remove until AMPA depolarization)
  • very good at fine tuning signals
  • always increases intracellular calcium levels, and actually generates more AMPA receptors
20
Q

Long term depression (LTD)vs Long term potential (LTP)

A

LTP

  • increases in potential of a synapse is present with an increase in AMPA receptors and NMDAR activity
  • requires gene transcription (which is only possible if NMDAR activities is high enough to phosphorylate genre transcription proteins

LTD:

  • decreases in potential at a synapse is present with not enough NMDA receptors
  • low levels of calcium intracellular prevent calmodulin = no/low protein phosphorylation
  • also less AMPA receptor expression at synapse

both are required for learnin

21
Q

Pathologies associated with glutamate signaling

A

Schizophrenia

  • deficiency of glutamine signaling in the cortex
    • this is hypothesized since non-competitive NMDA receptor antagonists (phencyclidine and ketamine) produce schizo effects*

Depression

  • overexpression of glutamine signaling can cause depression
  • treatment is with a ketamine antagonist on NMDARs

Alzheimer’s disease

  • overexpression of glutamine signaling
  • treatment is with memantine (non-competitive NMDA receptor antagonist)
22
Q

GABA and glycine neurotransmitter specifics

A

Note: glycine works almost exactly the same as GABA, just specifically in the spinal cord

Usually released by interneurons and act in an inhibitory fashion, however it is nonspecific

Two GABA receptors

  • A: target for sedatives
  • B: target for muscle relaxants
23
Q

Pathologies associated with GABA and glycine

A

Generalized convulsions

- impaired pathways of GABA causes irregular firing of neurons

24
Q

Acetylcholine neurotransmitter specifics

A

Signals through:
1) nicotinic (excitatory/ionotropic/sympathetic)

2) muscarinic (inhibitory/metabotropic/parasympathetic)
- the exception is it sympathetic for sweat glands

Functions in cognitive functions, motor control, and ANS activity

25
Q

Pathology associated with acetylcholine

A

Alzheimer’s disease

26
Q

Cholinergic receptors

A

Are found on muscarinic and nicotinic receptors

5 subtypes
- M1/3/5 = G(aq) protein coupled

  • M2/4 = G(aio) protien coupled
27
Q

Dopamine neurotransmitter specifics

A

Can be inhibitory and excitatory

Functions in basal ganglia communication, limbic system communication and regulation and motor circuit activity predominately

Also functions in:

  • cognition
  • motivation
  • mood
  • motor coordination
  • reward reflex
  • salience
28
Q

Difference between dopamine sup receptor types

A

5 types

D1/5 = increases cAMP/ excitatory

D2/3/4 = decreases cAMP/ inhibitory

29
Q

Pathological conditions associated with dopamine

A

All abuse disorders
- elevated levels of dopamine are found in all abuse-like disorders

Schizophrenia and though disorders
- elevated levels of dopamine activity/receptors are directly associated

Parkinson’s disease

  • lowered dopamine levels and signaling/receptors are present specifically in motor tracts
  • treat with L-DOPA, which is a precursor to dopamine
30
Q

Pathological conditions associated with NE defects

A

PTSD
- disrupted NE signaling

Parkinson’s
- degradation of locus coeruleus neurons decreases NE levels and pathway

31
Q

Review of NE receptor catagories

A

A1 = increases PLC levels and calcium levels

A2 = decreases cAMP levels and decreases calcium levels

B1/B2/B3 = increases cAMP and increases calcium levels

Affinity of NE with receptors is as follows
A1=a2 ; B1&raquo_space; B2

Most predominant in CNS

32
Q

Serotonin neurotransmitter specifics

A

Pretty much involved in all brain functions

Most important neurotransmitter in depression and bipolar disorders

Also plays a crucial role in peripheral 5-HT symptoms
- nausea, platelet activation, emesis

33
Q

Serotonin subtypes of receptors

A

There are 14, however they are best memorized via families

Family 5HT1
- decreases cAMP

Family 5HT2
- increase PLC and PLA2 levels

Family 5HT3

  • regulates cations in the brain
  • only serotonin receptor that is inotropic excitatory

Family 5HT4
- increases cAMP

Family 5HT5
- decreases cAMP

Family 5HT6/7
- increase cAMP

  • all are metabotropic receptors (except 5HT3)*

** 1-3 are most common for pharmacology targets**

34
Q

Histamine neurotransmitter specifics

A

Project diffusely through the hypothalamus/Brain and spinal cord

Functions are as follows

  • arousal
  • attention
  • feeding behavior
  • memory
  • circadian rhythm

3 receptor subtypes, however CNS is H3 subtype only

35
Q

Endocannabinoids

A

Not overly important right now

Signal through retrograde signaling and modulate neuronal specific functions (again not overly important right now)
- release form postsynaptic and modulate presynaptic neurons

36
Q

Peptide neurotransmitters and neuromodulators

A

Responsible for pain perception/transmission and modulation
- specifically substance P

Responsible for analgesia
- specifically enkephalins

Responsible for neural response to stress/ wakefulness/hunger
- specifically orexin

Neurology (65 decks)

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