08 27 2014 Neurotransmission

Question 1

What type of neuron responds to sensory inputs?

Answer 1

Pseudo-unipolar and Bipolar

Question 2

What type of neuron resounds to other synaptic inputs

Answer 2

Multipolar and bipolar neurons

Question 3

What is the resting potential of a neuron and how is this produced/maintained?

Answer 3

-65mV (-40mV to -90mV) Produced by osmotic and electrical forces, AND selective permeability Maintained by Na+/K+ ATPase

Question 4

RECALL: Are the concentrations of the following ions greater inside a cell or outside a cell: Ca2+ Cl- Na+ K+

Answer 4

All are greater outside except for K+ who is greater inside.

Question 5

what is a graded potential in a neuron?

Answer 5

response of neurons to inputs – reaches threshold and caused depolarization In sensory neurons a graded potential is called a receptor potential. Response can change based on potential.

Question 6

What causes a neuron to detect a more intense stimulus?

Answer 6

Action potential firing rate increases a sensory neuron’s response to a more intense stimulus. Higher firing rate = more neurotransmitter released = detect a more intense stimulus.

Question 7

What is a graded potential at a synapse?

Answer 7

electrical responses to synaptic input. changes in membrane potential that vary in size, as opposed to being all-or-none.

Question 8

What are the types of graded potentials?

Answer 8

-excitatory postsynaptic potentials (EPSPs) -opening of Na+ or Ca+ channels -cause depolarization -Inhibitory postsynaptic potentials (IPSPs) -opening of Cl- or K+ channels - hyperpolarize

Question 9

Describe ability of graded membrane potentials to impact system?

Answer 9

attenuate rapidly with distance from the point of stimulation. “impact factor” depends on their location and strength of synapse. ** has more of an impact if closer to where trigger is **

Question 10

Where is the trigger zone for sensory vs motor neurons?

Answer 10

Sensory neuron = near the “dendrite” end of a sensory neuron. Anatomoic axon/physiological dendrite – node of Ranvier? Motor neuron = axon hillock.

Question 11

Since graded potentials are summed, what is the threshold needed to initiate AP?

Answer 11

about 10mV at initial segment.

If threshold is reached at the trigger zone, one or more action potentials will occur.

Recall: if input is large, the firing rate of action potentials increase.

Question 12

What are the two types of summation?

Question 13

Spatial Summation?

Answer 13

refers to the number of inputs

Question 14

Temporal Summation?

Answer 14

refers to the timing of inputs.

Can add on and create even bigger responses.

Question 15

Example of inputs that modulate sensory signals in the spinal cord?

Answer 15

1. motivation/ attention
2. Arousal/anxiety levels
3. other sensory inputs
4. intesnity of input (comes in through DRG)

Question 16

Location of Synaptic inputs?

Answer 16

AD– Axodendritic

AA– Axoaxonal

AS– Axosomatic

DD– Dendrodendritic

Question 17

Where does PRE-synaptic inhibition occur?

Answer 17

Axon terminals

• axon projecting onto another axon
• affects one collateral
  1. an excitatory neuron fires
  2. an action potential is generated and travels down the axon
  3. an inhibitory neuron fires, blocking neurotransmitter release at ONE synapse (aka a collateral)

Question 18

Where does post-synaptic inhibition occur?

Answer 18

Prevents neuron from firing action potential –blocks at dendrites/cell body

• all outputs are affected.
  1. an excitator and an inhibitory presynaptic neuron fire.
  2. modified signals in post-synaptic neuron is below threshold
  3. no action potential triggered.
  4. no response from target cell.

Question 19

Review of channels when AP is created

Answer 19

Resting: Na+ inactivated

             K+ closed -- but they are leaky

Threshold: Na+ open– fast activaiton of Na+ channels

                K+  closed

Depolarization Peak: Na+ is inactivating

                                 K+ are opening -- slower activation

Refractory period: Na+ inactivated

                              K+ open

                              Na+ and K+ are closed again.

Question 20

How are AP propagated down an axon?

Answer 20

** Recently depolarized regions become refractory so that action potentials move unidirectionally.

1. Na+ channels locally open in response to stimulus = generate AP
2. depolarizing current flows passively down axon
3. local deplarization causes neighboring Na+ channels to open and generate AP.
4. Na+ channels there were once active are now inactive– refractory phase
5. process repeats down axon potential

Question 21

What does Action Potential conduction velocity depend on?

Answer 21

Myelination and axon diameter

• Myelination = increases speed
• Thicker axons have less resistance to current flow

Question 22

Name two demyelinating diseases:

Answer 22

1. Multiple Sclerosis
2. Guillain - Barre

Question 23

Multiple Sclerosis

Answer 23

Autoimmune inflammatory disorder.

• genetic/environmental factors
• Oligodendroglial myelin attacked – makes sense becuase oligodendrocites make myelin.
• CNS disease. usually begins with sensory loss

Diagnosed:

History of 2 or more deicits separated in neuroanatomical space and time.

• supported by MRI evidence of white matter lesions
• slowed CV (conduction velocity – EMG)
• CSF oligoclonal bands.

Question 24

Guillane- Barre?

Answer 24

Inflammatory- induced demyelination in peripheral nerves

Usually seen 1-2 weeks after a viral infection (can last for months)

Motor> sensory

Autonomic is also affected

Ascending pattern of weakness

Decreased nerve conduction velocity– measure in PERIPHERAL NERVES

Elevated protein in CSF w/o increase in WBC.

Question 25

Chemical Synaptic transmission

Answer 25

Pre-synaptic neuron releases one neurtransmitter into synaptic cleft. Neurotransmitter binds to receptors on post-synaptic neuron and can open/close post-synaptic channels (excitatory or inhibitory AP generation). Neurotransmitters are removed by glial uptake or enzymatic degradation

Question 26

Two types of post-synaptic receptors?

Answer 26

1. Ligand-gated ion channels - Ionotropic 2. G-protein coupled receptors - Metabotropic

Question 27

Ionotropic Receptor

Answer 27

Receptor linked directly to ion channels - ligand-gated ion channel Enable FAST responses. Provide information about what,when, where?

Question 28

Metabotropic receptors?

Answer 28

Receptor does not have a channel directly linked to it. - slow, long-term changes. - G-protein-coupled receptors 1. G-protein activation 2. G-protein dissociation and interaction (directly or indirectly) with ion channel. Responsible fro neuromodulation - **slow** = they hang around long enough that they can change the resting membrane potential = more excited/more inhibitory

Question 29

Ionotropic receptors: Excitatory vs. inhibitory neurotransmitters? (CNS vs. PNS)

Answer 29

Major Excitatory neurotransmitters PNS: ACh (nicotinic) CNS: glutamate Major Inhibitory neurotransmitters CNS: GABA or Glycine (spinal cord)

Question 30

Excitatory Amino Acid group neurotransmitters - Action and Location

Answer 30

**Glutamate** Location: CNS: everywhere; PNS: spinal ganglia Action in CNS: Fast and Slow excitation Slow inhibition (metaboropic)

Question 31

Inhibitory Amino Acid Group Neurotransmitters -location and Action

Answer 31

**GABA** location: CNS: everyhwere PNS: ganglia, gut Action in CNS: Fast and slow inhibition **Glycine** location: Brainstem AND spinal cord Action in CNS: Fast inhibition

Question 32

**Glutamate** 1. Type of neurotransmitter 2. Origin (location of cell bodies) 3. Function 4. receptor subtype 5. Location of receptor 6. receptor functions 7. Glutamate toxicity

Answer 32

1. Major excitatory amino-acid neurotransmitter 2. Entire CNS 3. Fast and slow excitation; slow inhibition (metabotropic). Requried for long-term potentiation of (learning and memory) 4. AMPA and NMDA 5. Location of cell bodies: Entire CNS 6. AMPA-- ionotropic Na+/K+ passage -- net effect =excitatory NMDA --Mg2+ plug that is released when glutamate is present. Na+, K+ and Ca+ passage (Na+ and Ca2+ go into cell, K+ comes out of cell) 7. Glutamate toxicity Trauma/disease impaire ATp-generation = increased glutamate release or decrease glutamate reuptake. -NMDA channels allow Ca2+ to leak into cells--\> autodigestion. Leads to multiple seizure Disease thought to be assocaited with glutamate toxicity: ALS, Alzheimer's, tumors, oxygen deficiency, ischemia trauma.

Question 33

**GABA** 1. Type of neurotransmitter 2. Origin (location of cell bodies) 3. Function 4. receptors 5. Location of receptor 6. receptor functions 7. Molecules that act on GABA receptors

Answer 33

1. amino acid -- inhibitory 2. Everywhere in CNS 3. Fast and slow inhibition 4. GABA- gated Cl- channels (GABA a receptor): Ionotropic recepotrs that open Cl- channels GABA b - metabotropic receptors open K+ or close Ca 2+ channels 5. CNS: everywhere; PNS: Ganglia and gut 6. Inotropic opening of Cl- channels 7. molecules that can act on GABA receptors: Benzodiazepine (anti-anxiety), Ethanol, Barbituate, and Neurosteroids, GABA.

Question 34

**Glycine** 1. Type of neurotransmitter 2. Origin (location of cell bodies) 3. Function 4. receptors 5. Location of receptor 6. receptor functions

Answer 34

1. Amino Acid- inhibitory 2. Spinal cord (maybe brain stem too) 3. Fast inhibition in CNS 4. Glycine receptors 5. Location: spinal cord and brainstem 6. Ionotropic: ligand-gaited Cl- channels (Similar to GABA a receptor) - inhibitory!

Question 35

Catecholamines that come from Tyrosine?

Answer 35

Norepninephrine, epinenphrine, and dopamine

Question 36

**Norepinephrine** 1. Type of neurotransmitter 2. Origin (location of cell bodies) 3. Function 4. receptors 5. Location of receptor 6. receptor functions 7. Drugs that stimulate NE release?

Answer 36

1. Biogenic Amine-- Catecholamine from tyrosine 2. Locus ceruleus and Lateral tegmental areas (Pons) 3. Slow excitation; Modulates pina, role in sleep-wake cycles and attention; post-synaptic ganlian. 4. alpha and beta subtypes 5. CNS: everywhere; PNS: sympathetic ganglia 6. Neuromodulation AND sympathetic functions 7. Amphetamines, Methylphedinate (Ritalin)

Question 37

**Dopamine** 1. Type of neurotransmitter 2. Origin (location of cell bodies) 3. Function 4. receptors 5. Location of receptor 6. receptor functions 7. three projections? (just name them)

Answer 37

1. Biogenic Amine-- Catecholamine from tyrosine 2. Substancia Nigra, ventral tegmental are, pars compaccta (Midbrain) 3. Slow inhibition or excitation motor control memory motivation reward addiction maternal behavior sensory processes 4. D1- D5 5. CNS: Everywhere 6. Neuromodulation 7. - Mesostriatal (nigrostriatal) pathway - Mesolimbic pathway - Mesocortical pathway

Question 38

Dopamine pathway-- Nigrostriatal Pathway where does it start --\> where does it go - functions - what happens when dysfunction? - treatment

Answer 38

arises from substantia nigrapars compacta ---\> cuadate and putament (thalamus) control of movement disfunction= Parkinson's disease Treatment: dopamine agonists

Question 39

Dopamine pathway -- **Mesolimbic** - where does it start --\> where does it go - functions - what happens when dysfunction? - treatment

Answer 39

Arises from ventral tegmental area (some from substancia nigrapars compacta) to limbic structures: - Medial orbital frontal cortex - Nucleus accumbens - Cingulate cortex - Hippocampus and parahippocampal gyrus - Amygdala Reward pathway (addiction) Damage = positive symptoms of schizophrenia --\> hallucinations Treatment: dopamingeric antagonists

Question 40

Dopamine pathway -- **Mesocortical pathway** - where does it start --\> where does it go - functions - what happens when dysfunction? - treatment

Answer 40

ventral tegmental area (some from substancia nigrapars compacta) to prefrontal cortex. Functions: working memory and atttional aspects of motor initiation. Damage: cause cognative deficitis and hypokinesia (decrease movement) in Parkinson's disease. Can also cause NEGATIVE symptoms of Schizophrenia

Question 41

**Seratonin (5-HT):** 1. Type of neurotransmitter 2. Origin (location of cell bodies) 3. Function 4. receptors 5. Location of receptor 6. receptor functions (aka how does receptor work) 7. Drugs that affect 5HT systems?

Answer 41

1. Biogenic Amines 2. Raphe nuclie -- midbrain, pons, and medulla 3. Slow inhibition or excitation, fast excitation, sleep-wake cycle, mood, depression, anxiety, pains 4. N/A 5. CNS: everywhere 6. N/A 7. Prozac : blocks 5-HT reuptake MDMA, MDEA ("ecstacy") increases 5-HT efflux and increses sensory experiences and affect social relationships.

Question 42

**Acetylcholine:** 1. Type of neurotransmitter 2. Origin (location of cell bodies) 3. Function 4. receptors 5. Location of receptor 6. receptor functions (aka how does receptor work) 7. What happens when Ach is blocked?

Answer 42

1. Biogenic Amines 2. Nucleus Basilis of the basal forebrain, septal nuclei, and nucleus of diagonal band, and tegmentum of the pons 3. Fast excitation (nicotinic ionotropic), Slow excitation or inhibition (muscarinic metabotropic), memory, alertness 4. Nicotinic and muscarinic 5. CNS: cortex and spinal cord; PNS: parasympathetic ganglia (muscle) 6. N: ganglion, skeletal muscles M: Smooth musle, contraction, sweat gland secretion 7. causes delirium. Nucleus basalis degerates in Alzheimer's disease

Question 43

**Opiates** 1. Type of neurotransmitter 2. Origin (location of cell bodies) 3. Function 4. receptors 5. Location of receptor 6. receptor functions (aka how does receptor work) 7. 3 classes?

Answer 43

1. Neuropeptides 2. Periaqueductal grey of the midbrain, Thalamus, Ventral tegmental area, nucleus accumbens, amygdala, spinal cord 3. regulates pain 4. Mu, Kappa, Delta 5. (same as number 2) 6. N/A 7. 1. Enkephalin-- spinal cord--\> periaqueductal grey (PAG) -- regulates pain 2. Endorphins-- hypothalamus--\> PAG --\> Spinal Cord -- regulates pain-analgesia - morphine is agonist 3. Dynorphin -- located in PAG

Question 44

Unconventional neurotransmitters

Answer 44

Endocanabinoids: act as neuromodulator to decrease transmission of pain (medical marijuana) Cannibis (marijuana): alters perception, incresed sociability, induced euphoria. Possible role in mood disorders, anxiety and appetite control. Approved pain relief in MS. Nitric oxide: gas-- may actually be involved in neurodegenerative processes.