Neuro 1

Front 1

General Fx of:

1) Microcircuit

2) Macrocircuit

3) Nanocircuit

Back 1

1) Reflexes, Sensory Information, Locomotion, Learning and Memory

2) Object Recognition, Cognition

3) Learning and Memory, Neuronal Rhythmicity

Front 2

What is Stimulus DURATION proportional to?

Back 2

NUMBER of Action Potentials

Front 3

What is Stimulus INTENSITY proportional to?

Back 3

FREQUENCY of Action Potentials

Front 4

Examples of Feedback/Recurrent Inhibition (2):

Back 4

1) Renshaw Cell (an Interneuron) in Spinal Cord

2) CA3 Pyramidal Cells in Hippocampus (CA3 Excite Basket Cells, Basket Cells Feedback to Inhibit CA3 Cells)

Front 5

In a Nanocircuit, what is required for OSCILLATIONS to occur?

Back 5

Excitatory drive is CONTINUOUS

Inhibitory process wanes in its effectiveness

Front 6

4 Gait Types:

Back 6

All Achieved with a SINGLE Recurrent Inhibition RING Circuit

1) Walk: Left Front, Right Hind, Right Front, Left Hind

2) Trot: Left Front and Right Hind in Phase and 180 degrees OUT of phase with Right Front and Left Hind

3) Bound: Left Front and Right Front In Phase and 180 degrees OUT of phase with Right Hind and Left Hind

4) Gallop: Variant of Bound, with SLIGHT phase difference between R/L Front and R/L Hind Limbs

Front 7

Where are memories?

Back 7

DISTRIBUTED in a Neuronal Network!

NOT in any ONE Synapse!

Front 8

Hebb Learning Rule:

Back 8

To change synaptic strength, BOTH the Presynaptic AND the Postsynaptic cell MUST BE ACTIVE

Front 9

fMRI

Back 9

Identify areas of the brain that are ENGAGED in COGNITIVE TASKS

Front 10

DTI (Diffusion Tensor Imaging)

Back 10

Visualization of Pathways LINKING one brain region to another.

Front 11

Netrins

Back 11

Can Bind 2 Types of Axonal Receptor:

1) DCC/UNC-40 = ATTRACTIVE

2) UNC-5=REPULSIVE

Front 12

Semaphorins

Back 12

Functions:

1)Growth Cone COLLAPSE

2) Axonal STEERING

3) Axonal BRANCHING

4) Axon Terminal ARBORIZATION

Front 13

Agrin

Back 13

Neve Derived

Organizes Post-Synaptic Differentiation (Receptor Deficiencies)

Front 14

Synapse Elimination Mechanisms

Back 14

1) Activity-Dependent

2) Direct (Compete for TROPHIC Factors supplied by Target Cell)

3) Indirect (Cell selects favored axon)

Front 15

What is the survival of a neuron often dependent on?

Back 15

Trophic Factors produced by the Target Tissue

Most Common = Nerve Growth Facor (NGF). Cells bind NGF, internalize, and RETROGRADELY transport it, PREVENTING DEATH.

Front 16

Axonal Regeneration

Back 16

PNS ONLY (Generally, very rare in CNS)!

Why?
1) CNS LACKS necessary Trophic Factors (ie NGF, laminin, fibronectin) which Prevent degradation of damaged axons!
2) Oligodendrocytes express Growth Inhibitory Molecules that BLOCK axon regrowth.

Front 17

Colchicine and Axonal Regeneration

Back 17

INHIBITS Axonal Regeneration

Colchicine DEPOLYMERIZES Microtubules = Blocks Axonal Transport

For Axonal Regeneration, this means the NGF CANNOT be retrogradely transported, and the cell will NOT regenerate!

Front 18

Wallerian Degeneration

Back 18

The loss of the DISTAL segment of a cut Axon

Degenerates SLOWLY, up to 1 month!

Front 19

What is an Auto-Association Network associated with?

Back 19

Learning and Memory

Front 20

Microtubule Associated Proteins (MAPs) in Dendrites vs Axons:

Back 20

HIGHER Molecular Weight in DENDRITES! Ex. MAP2

Axons have LOWER MW MAP. Ex. Tau

Front 21

What are present in LARGER, but NOT SMALLER Dendrites?

Back 21

Rough ER and Ribosomes

Front 22

Where are Microfilaments MOST DENSE in an Axon?

Back 22

Nodes of Ranvier

Front 23

Beyond the Initial Segment, what does the Axon LACK?

Back 23

Rough ER and Free Ribosomes

Front 24

Is this an Axon or a Dendrite?

Back 24

Locate Region of Impulse Initiation! --> This is the AXON

Region is analogous to the Initial Segment

Front 25

Where are BIPOLAR Neurons found?

Back 25

Retina and Olfactory Bulb

Front 26

Multipolar Neurons

Back 26

Most Common

Subtypes:
1) Golgi Type 1 - Large, usually Interneurons
2) Golgi Type 2 - Small

Front 27

Function of Neurofilaments?

Back 27

In Axons, Neurofilaments are MORE Abundant than Microtubules

1) Maintenance of Shape
2) Maintenance of Mechanical Strength

Involved in Alzheimer's Disease: Modified Neurofilaments form Neurofibrillary Tangles

Front 28

Nissl Substance

Back 28

Rough ER + Ribosomes

Front 29

Macroglia Types:

Back 29

1) Oligodendrocytes

2) Ependymal Cells

3) Astrocytes

Front 30

Protoplasmic Astrocytes

Back 30

Gray Matter

Irregular Cell Body

Sheet-Like Processes that CONFORM to shape of surrounding neurons/vessels.

Nucleus is Ellipsoid or Bean-Shaped

Front 31

Fibrous Astrocytes

Back 31

White Matter

Smooth Cell Body

Processes form end feet on blood vessels, ependyma, and pia. NO Sheets.

Abundance of Glial Fibrils (metal stains) arranged in Parallel Arrays

Nucleus is Ellipsoid or Bean-Shaped

Front 32

Glial Limitans

Back 32

Complete lining around the External surface of the CNS formed by ASTROCYTES

Front 33

Perivascular Feet

Back 33

Barrier around Blood Vessels formed by ASTROCYTES

Front 34

Oligodendrocytes

Back 34

1 can myelinate many neurons!

In White Matter (Majority) = Interfascicular Oligodendroglia

In Gray Matter = Perineuronal Satellite Cells

Front 35

Are Nodes of Ranvier bare?

Back 35

NO!

They are either:
1) Sites of Axon Branching
2) Sites of Synaptic Contact
3) Covered with Various Glial Processes

Front 36

Choroid Plexus

Back 36

Modified Ependymal Cells various regions of the Ventricles

Modification: Lie on a BASEMENT MEMBRANE over a rich bed of Vasculature and CT (normal ependyma do NOT)

Front 37

Microglia

Back 37

Originate from MESODERM!

More abundant in Gray matter, but are generally inconspicuous in NORMAL tissue.

Elongated or Triangular Nuclei

Front 38

Nernst Equation:

Change [K] by a factor of 10 =

Back 38

60 mV CHANGE in Potential

Front 39

Time Constant (T)

Back 39

T = RC
(R= Resistance and C = Capacitance)

The amount of time required for the change in potential to reach 63% of its final value.

Small Time Constant = More Rapid

Front 40

Space Constant

Back 40

Space Constant = SqRt[dRm/4Ri]
(d= Diameter, Rm = Membrane Resistance, Ri = Internal Resistance)

The Distance a potential will spread along an axon in response to a SUBTHRESHOLD Stimulus

Front 41

Propagation Velocity

Back 41

Proportional to Space Constant

Inversely Proportional to Time Constant

Thus, Proportional to Space Constant/Time Constant

Front 42

In a SINGLE ACh Vesicle:

1) How many channels could be opened?

2) How many Molecules of ACh are inside?

3) How much Membrane Potential change?

Back 42

1) 1,000 ACh Channels Opened/ Vesicle

2) 10,000 Molecules ACh/Vesicle

3) 0.5 mV Change/Vesicle (50 mV Change = 100 Vesicles)

Front 43

What does the AMPLITUDE of a MEPP depend upon?

Back 43

Amount of ACh in a SINGLE (typically) Vesicle

MEPP is INDEPENDENT of Calcium Influx and Concentration of Extracellular Calcium

Front 44

How is the EPSP in the CNS (ie Sensory 1A Afferent --> Extensor Spinal Motor Neuron) different from the NMJ EPSP?

Back 44

1) NT = Glutamate (not ACh)

2) Synaptic Potential Amplitude = 1 mV (50 mV at NMJ)

Front 45

FX of:

Tetrodotoxin (TTX), μ-Conotoxin (μ-CTX), Saxitoxin (STX)

Back 45

Block Pore of VOLTAGE DEPENDENT Na CHANNELS

Front 46

FX of:

ω-Conotoxin (ω-CTX), Funnel Web Spider Toxin (ω-Aga)

Back 46

Block certain types of VOLTAGE DEPENDENT Ca CHANNELS

Front 47

FX of Apamin

Back 47

Blocks certain types of Ca ACTIVATED K CHANNELS

Front 48

FX of Charybdotoxin (ChTX)

Back 48

Blocks certain types of Ca ACTIVATED K CHANNELS + VOLTAGE DEPENDENT K CHANNELS

Front 49

FX of Curare (d-tubocuraine):

Back 49

Competitive Inhibitor of NICOTINIC ACh RECEPTORS

Front 50

FX of α-Bungarotoxin:

Back 50

Competitive and Highly Irreversible Inhibitor of NICOTINIC ACh RECEPTORS

Front 51

FX of Picrotoxin

Back 51

Blocks GABAa Receptor

Front 52

FX of Strychnine

Back 52

Blocks GLYCINE RECEPTOR

Front 53

FX of Tetanus Toxin and Botulinum Toxin

Back 53

Both have Zinc-Dependent Protease Activity. Cleave Synaptic Vesicle Proteins DIFFERENT regions:

Tetanus - CNS, blocking NT Release

Botulinum - NMJ. blocking ACh Release

Front 54

NMDA and LTP

Back 54

NMDA is Permeable to Ca (AMPA is NOT), in addition to Na and K.

This Ca triggers long-term changes in Synaptic Strength via 2 mechanisms:

1) Insertion of additional AMPA Receptors

2) More NT is released

Front 55

Synapsin

Back 55

Binds Vesicles, Frees them from Actin Microfilaments so they can Mobilize to Active Zone

Activity requires Ca Dependent Phosphorylation

Front 56

Vesicle Docking/Priming Proteins

Back 56

Vesicle Proteins:
1) Synaptotagmin
2) VAMP

Plasma Membrane Proteins:
1) Syntaxin
2) SNAP-25
3) n-sec-1 (must be DISPLACED)

Trimeric Complex = VAMP, Syntaxin, SNAP-25

Synaptotagmin Binds Ca, and Initiates FISSION

Front 57

What targets SNAP-25?

Back 57

Botulinum Toxins A and E

Front 58

What targets Syntaxins?

Back 58

Botulinum Toxin C1

Front 59

What targets VAMPs?

Back 59

Botulinum Toxins B, D, F, G AND Tetanus Toxin

Front 60

Retrograde transport Clinical Relevance?

Back 60

Several Viruses, such as Rabies and Herpes, are transported to the CNS via this pathway

Front 61

When does ACh have a Sympathetic Effect in the Autonomic Nervous System?

Back 61

1) Sweat Glands

2) Piloerector Muscle (Makes Hair Stand Up)

Front 62

Black Widow Spider Venom (BWSV)

Back 62

Stimulates ACh Release!

Front 63

Where does ACh have INHIBITORY actions?

Back 63

1) Certain Smooth Muscles

2) Cardiac Muscle

Front 64

What is ONLY found in Cholinergic Neurons and NOWHERE ELSE?

Back 64

Choline Acetyl Transferase (CAT)

Front 65

Isopropylfluoroesters

Back 65

Irreversibly Inhibit ACh Esterase via Carbamylation (inactivates both the acetyl AND choline binding domains)!

Examples:
Insecticides
Gases used in Bio Wars

Front 66

Eserine (Physostigmine)

Back 66

Reversibly inhibits ACh Esterase

Used to Diagnose/Treat Myasthenia Gravis

Front 67

The Roles of CNS ACh and Behavior:

Back 67

Nicotinic - Little is known, reinforcement behavior (addiction)

Muscarinic - Important mediators of behavior in the CNS! 2 known roles:
1) Modulate Motor Control circuits in Basal Ganglia
2) Participate in Learning and Memory

Front 68

Alzheimer's Disease

Back 68

CNS Deterioration

Progressive Dementia

Marked DECREASE in [ACh] in Cortex and Caudate Nucleus.

Front 69

Myasthenia Gravis

Back 69

Autoimmune Destruction of NMJ Nicotinic ACh Receptors

Front 70

CNS Dopamine (DA)

Back 70

DA Cell Bodies in Midbrain

Four DA Systems:
Mesostriatal System
Mesolimbocortical System
Periventricular System
Tuberohypophyseal System

Front 71

CNS Norepinephrine (NE)

Back 71

NE Cell Bodies in Pons and Medulla

Three Main Groups:
Locus Coeruleus Complex
Lateral Tegmental System
Dorsal Medullary System

Terminals LACK conventional synaptic junctions. VOLUME TRANSMISSION, released and diffuses.

Front 72

CNS Serotonin (5-HT)

Back 72

5-HT Cell Bodies in 2 Clusters:
1) Caudal System in Medulla
2) Rostral System in Midbrain

Front 73

CNS Histamine

Back 73

Cell Bodies in Basal Posterior Hypothalamus

Also released by Mast Cells, so hard to distinguish CNS Histamines role.

Front 74

Vitamin B6 and Catecholamine/Serotonin/Histamine Synthesis

Back 74

Required for AADC to form Dopa or 5-HT

Required for Histidine Decarboxylase to form Histidine

Front 75

Vitamin C and Catecholamine Synthesis

Back 75

Required for conversion of Dopamine to NE via Dopamine Beta Hydroxylase (first step which occurs in the storage vesicle)

Front 76

How does Histamine synthesis differ from Catecholamine/Serotonin synthesis?

Back 76

Does NOT require Hydroxylation!

Single Step, Decarboxylation of Histamine (also requires Vit B6)

Front 77

α Receptors (NE/E)

Back 77

α1 = Often excitatory, via IP3.

α2 = Inhibitory acting via decreased cAMP

Front 78

β Receptors (NE/E)

Back 78

Actions can be mimicked by Isoproterenol!

Mostly Inhibitory (exception-cardiac) and act through increased cAMP

Front 79

DA Receptors

Back 79

Two Families:

1) D1 Family:
-D1, D5
-Increase cAMP, Negative influence on Excitability of Target
-Post Synaptic

2) D2 Family:
-D2,D3,D4
-Decrease cAMP, Increases Excitability of Target
-Presynaptic

Front 80

5-HT3 Receptor

Back 80

Unique among Serotonin Receptors because it is NOT a GPCR!

Ligand Gated Ion Channel!

Front 81

Actions of Cocaine/Tricyclic Antidepressants and Amphetamines on MAs

Back 81

Cocaine/Tricyclic Antidepressants INHIBIT the MA Reuptake Transporter

Amphetamine REVERSES the direction of transport.

Both INCREASE [MA] in Extracellular Space

Front 82

What would you measure to detect the following:

1) ANS Activity

2) Central NE Function

3) Central DA Function

4) Adrenal Medulla Activity or a Tumor There

Back 82

1) VMA

2) MHPG

3) HVA and DOPAC

4) Metanephrine

Front 83

Dopamine and Motivated Behavior

Back 83

Involved in 2 Phases:

1) Appetite Phase (Ventral Striatum ie Nucleus Accumbens)

2) Consumption Phase (Dorsal Striatum ie Caudate-Putamen).

Front 84

NE and Behavior

Back 84

Involved in Attention and Arousal - regulate an organisms vigilance.

Locus Coeruleus (LC) and α2 Receptors are Important here

Front 85

Serotonin and Behavior

Back 85

Involved with:

1) Appetite (negative regulator of motivation to eat Carbs)
2) Sleep
3) Aggression (Low 5-HT --> High Aggressiveness/High RIsk Taking Behavior --> Low Dominance)

Front 86

Fenfluramine

Back 86

Serotonin Uptake Inhibitor

Used as a Obesity Pill (Serotonin negatively regulates motivation to ingest Carbs)

Front 87

Dopamine and Clinical Implications

Back 87

1) Psychiatric Illnesses - Schizophrenia - TOO MUCH DA

2) Movement Control Disorders - Parkinsons Disease - TOO LITTLE DA

Front 88

NE and Clinical Implications

Back 88

Unipolar and Bipolar Disorders

Low [NE] = Depression

High [NE] = Mania

Front 89

Serotonin (5-HT) and Clinical Implications

Back 89

All due to having TOO LITTLE Serotonin EXCEPT FOR Schizo

1) Depression associated with SUICIDE

2) OCD

3) Agression

4) Eating Disorders

5) Schizophrenia (also associated with DA) - TOO MUCH 5-HT

6) Migraine Headaches

7) Insomnia

Front 90

AA NT Biosynthesis

Back 90

Products of Intermediary Metabolism with 1 EXCEPTION - GABA

GABA produced by GAD (ONLY in Neurons)

Front 91

Strychine

Back 91

Blocks binding of Glycine to its receptor, Inhibiting an Inhibitor!

Causes Asphyxiation due to inability to relax the diaphragm

Front 92

GABA Shunt

Back 92

When excess GABA is taken up into Glial Cells, it is first converted back to Glutamate via GABA Transaminase (GABA-T) and alphaketoglutarate as a substrate

Front 93

Receptors for AA NTs

Back 93

ALL can be either Ionotropic or GPCR EXCEPT FOR GLYCINE

Glycine - Ionotropic ONLY!

Front 94

NMDA Receptor

Back 94

Requires binding of Glutamate (presynaptic) AND Depolarization (postsynaptic, to free Mg block)

Also requires binding of Glycine from ECF.

Results in LARGE influxes of Ca (Na and K also)

Associativity - Involved in learning.

Front 95

GABAa Receptor

Back 95

Largely Postsynaptic

Opens Cl Channel (Ionotropic)

Multisubunit (binds modulators)

Front 96

GABAb Receptor

Back 96

Largely Presynaptic

Alters 2nd Messengers (Metebotropic)

Single Subunit

Front 97

GABAa Receptor Subunits/Drug Targets

Back 97

GABA binds Alpha Subunit

1) Benzodiazepines (Valium, Librium) - bind Gamma - AGONIST

2) Barbiturates - bind Alpha AND Beta - AGONIST

3) Picrotoxin - Blocks Cl flow through receptor - ANTAGONIST

Front 98

Strychnine

Back 98

Rat Poison

Blocks Glycine Receptor

Front 99

Tissue Plasminogen Activator (tPA)

Back 99

Clot Breaking Agent

Used after STROKES to reestablish blood flow so ATP can be produce and Glutamate be pumped back into Neurons

Front 100

Diseases associated with Glutamate:

Back 100

1) Alzheimer's

2) Huntington's Chorea

Front 101

Diseases associated with GABA

Back 101

Epileptic Seizures - TOO LITTLE GABA. Treated with Barbiturates(Agonists for GABA binding).

Mood Disorders(Generalized Anxiety) - TOO LITTLE GABA. Treated with Benzodiazepines (Agonists for GABA binding).

Front 102

NT Receptor Transmembrane Spanning Domains

Back 102

3
____
1) Non-NMDA Glut R
2) NMDA Glut R

4
_____
1) Nicotinic ACh R
2) GABAa R
3) Glycine

7
____
ALL GPCRs! (Muscarinic ACh, MA Rs, GABAb, Neuropeptides, Glutamate GPCR)

12
___
Reuptake Transporters

Front 103

Neuromodulators

Back 103

Effects potentiate or depress effects of a SECOND transmitter.

Front 104

Neuropeptide Families

Back 104

1) Tachykinins
2) Insulins
3) Somatostatins
4) Gastrins
5) Opioids

Front 105

Synthesis of Neuropeptides

Back 105

Occurs by proteolytic cleavage of a larger precursor WITHIN the transport vesicle!

Front 106

Diversity Generation in Neuropeptides:

Back 106

1) Differential Splicing
2) Packaging Different Proteases
3) Post-Translational Modifications

Front 107

What is unique about Neuropeptide Release/Termination?

Back 107

Release - No docking required

Termination - No reuptakers

Front 108

What NT receptor has HIGHEST affinity for its substrate?

Back 108

Neuropeptides!

Why? Compensates for Non-Directionality of Release!