Unit 2 Exam

Peak of action potential

Peak of action potential

A rush of sodium into the cellular membrane, causes the membrane to become +40mv; this triggers the outward flow of K+

Overshoot / relative refractory period

Rapid efflux of K+ out of the cellular membrane (due to Na+ coming in), causes the inside to become -80mv; hard to get cell to re-fir during this time

Sodium/Potassium Pump

responsible for re-establishing the resting membrane potential (-70 mv) by extruding Na+ and bringing back in K+; occurs at Nodes of Ranvier

Saltatory conduction

conduction of action potential by myelinated axons; action potential

Voltage dependent

ion channel that opens or closes according to the value of the membrane potential

Heteroreceptors

activate Ca 2+ ion channels; Ca enters the membrane

Exocytosis

the process of activated enzymes propelling vesicles along microtubular and exporting them out of the presynaptic membrane and into the synapse as neurotransmitters

SNARES

long-chain proteins that mediate (allows for the movement) of exocytosis; serve as tethers

synaptotagmin

serves as Ca sensor and binds with it; alerts SNARES to tie together (t and v)

Re-uptake

the re-entry of NTs just liberated by a terminal button back through its membrane → terminates the postsynaptic potential

Enzymatic breakdown

the destruction of a neurotransmitter by an enzyme after its release; breaks NT into an inactive form

metabolite

the broken-down substance in enzymatic breakdown

Autoreceptors

receptors on the axon terminal that become active when the synapse begins to get full; inhibits the release of additional neurotransmitters by closing Ca channels

Three ways of clearing out synapse

reuptake, enzymatic breakdown, autoreceptors

Agonist

anything that increases the activity of neurotransmitters

Antagonist

decrease the activity of neurotransmitters

Neurotransmitters

A chemical that is released from a nerve cell which thereby transmits an impulse from a nerve cell to another nerve, muscle, organ, or other tissue

What are the criteria for something to be considered a neurotransmitter?

• chemical is released onto a target cell

• substance exists in presynaptic axon terminal and synthesized in presynaptic cells

• is released when action potential reaches axon terminals

• receptors for the substance exist on the post-synaptic cell

• blocking substance release prevents changes in postsynaptic cell

• can activate (EPSP or IPSP) more than one neuron at a time

Monoaminoxidase (MAO)

degrading enzyme that takes NTs that weren’t placed in vesicles and breaks them down

Seven steps in NT action

1. synthesis

2. storage in vesicles

3. breakdown of any NT leaking from vesicles

4. exocytosis

5. activation of postsynaptic receptors

6. inhibitory feedback via autoreceptors

7. deactivation

synthesizing/synthetic enzyme

an enzyme that uses precursors to make something

Acetylcholine (Ach)

accomplishes all muscle movement; produces EPSPs for voluntary muscles and IPSPs for involuntary muscles

colinergic

receptor for Ach

Cognitive function of Ach

allows voluntary muscle movement, inhibits parasympathetic NS and actives sympathetic NS, allows for REM sleep

nicotinic receptor (EPSP)

excites voluntary muscles through the release of Ach

muscarinic receptor (IPSPs)

inhibits involuntary muscles and the parasympathetic NS

RAS (reticular activating systems)

controls overall brain arousal

How does Ach induce REM sleep?

the Pons releases Ach to inhibit RAS (part of the Pons)

Dopamine (DA)

associated with pleasure and motivation; activate the nucleus accumbens and septum; can be a precursor for norepinephrine

Overactivity of dopamine in _____ leads to …

mesolimbic system leads to hallucinations and delusions

neuroleptic

a common type of antipsychotic that blocks dopamine receptors

Mesolimbocortical Dopaminergic system

made up of the mesocortical and mesolimbic systems

associated with activity of the limbic system, emotional experiences, learning and memory, and ability to form long-term goals; activates the nucleus accumbens, amygdala, hippocampus, and pre-frontal cortex

mesolimbic

controls limbic system

mesocortical

associated with PFC

Mesostriatal (Nigrostriatal) Dopaminergic system

associated with activity of the basal ganglia; not affected in schizophrenia but if damaged leads to Parkinson’s disease

basal ganglia

area of the brain associated with the passage of motor information from the PFC throughout the brain

Parkinson’s Disease

damage to dopaminergic cells in the basal ganglia leading to loss of control over voluntary movement

Epinephren

a hormone associated with arousal

Norepinephrine (NE)

a.k.a Adrenaline, #1 excitatory NT; controls overall levels of arousal and wakefulness and regulates circadian cycle, creates EPSPs which enhance cortical activity, activates RAS, (as a result) limbic system and dopamine

Noradrenergic receptors

largely excitatory, similar in chemical nature to epinephrine

Circadian cycle

daily cycle of arousal

Why do many antidepressant medications activate NE?

activation of NE combats lack of energy, arousal, and pleasure (depression symptoms)

Serotonin (5-HT)

5-hydroxytryptophan; a regulatory NT affecting many neural functions (has many different types of receptors)

serotonergic

a receptor for serotonin

selective serotonin reuptake inhibitors (SSRI)

anything (ex. drugs) that almost exclusively inhibits the re-entry of serotonin; agonist

Relationship between 5-HT, NE, DA, and Depression

serotonin activates enzymes that increase receptors’ affinity for norepinephrine and dopamine; low serotonin linked to low NE and DA (lack of arousal and pleasure = depression symptoms)

Raphe Nuclei

can inhibit transmission of pain to brain by activating endogenous opioids (ie. endorphins); activated by 5-HT; inhibits/excites PFC

Endorphins

a type of endogenous opioid that inhibits physical pain; natural defense against pain

Enkephalins

inhibits short-term emotional pain

Dynorphins

inhibit long-term (cortical) pain

GABA

the primary inhibitory NT in the body important for controlling brain’s electrical activity and defend against stress and anxiety

underactivity in GABA…

leads to anxiety and out of control brain activity (eg. seizures)

Benzodiazepines

primary anti-anxiety drugs; activates and increases affinity of companion receptors including GABA receptor (an allosteric activator)

gabaminergic

a GABA receptor or associated system

Glutamate (Glu)

an excitatory NT that increases connections and formation of memory in hippocampus; associated with long-term potentiation

NMDA

an important glutamate receptor that allows for physical change of neurons that allows for the formation of new memories; promotes dendritic growth

glutaminergic

a neuron that uses glutamate

Endogenous Opioids

a NT that regulates the body’s response to pain by releasing EPSPS for pain; a natural pain reliever; activated by Raphe Nuclei and 5-HT

Lithium

activates GABA

Neuropharmacology

the study of how substances affect our nervous system and behavior; usually starts with animal research

Half-time

time it takes for 1/2 of the drug to leave the body; used as a safety andmaintenance factor

How long does it take for drug to become negligible in the body?

3-5 half-lives; negligibility is less than 5%

Negligible

not important, relevant, or dangerous

Drug metabolism

the process by which the body breaks down and converts medication into altered chemical substances

When the drug concentration is around 5% it is said to be…

negligible; 4-5 half-lives must elapse until the drug is eliminated

Dose-response curve

a graph of the relationship between drug doses and the effects

Therapeutic window

many drugs only work at specific doses; high and low often have little effect

Nonmonotonic DRC

a DRC that is normal up to a point but then reverses and the measured response begins to decrease with larger doses

Minimum effective dose (ED50)

lowest dose to produce desired effect in 50 % of clinical subjects

Median Toxic dose (TD50)

dose which produces first signs of toxicity in 50%; high build-up in blood

Threshold dose

smallest dose to produce detectable change

Maximum response/maximum dose

the greatest degree of response that can be achieved with a specific drug

Partial agonist/antagonist

a drug of moderate efficacy

Therapeutic index (TI)

the separation between the effective dose and a toxic one; TI = TD50/ED50

Clinical efficacy

refers to the degree to which a drug is able to induce a given effect

Potency

the amount of a drug needed to produce a desired effect

Affinity

capacity of a compound (drug) to maintain contact or be bound to a receptor

Binding affinity

the degree of chemical attraction between a ligand and a receptor

Tolerance

when there’s a decreased susceptibility or increase in the amount of drug needed

Differential tolerance

tolerance to one part/effect of a drug but not the other effects

anxiolytic

used to treat anxiety

metabolic tolerance

an organ system’s efficacy at eliminating drug

Hepatic Microsomal Enzyme (HME)

breaks down drug to metabolites do they become ineffective and easier to eliminate; repeated substance use creates more HMEs

Cross-tolerance

tolerance to one drug gives pre-existing tolerance to another

metabolic up regulation

increase of HME amount leading to faster breakdown of drug

functional tolerance

target tissue may show altered sensitivity to the drug due to physical change of receptors on the post-synaptic membrane

up regulation

increased density of post-synaptic membrane receptors

down regulation

decreased density of post-synaptic membrane receptors

Dangerous interaction

If two substances taken at the same time have the same HMEs, the HMEs could focus on breaking down one substance and not the other exacerbating the effects of the other substance

Biotransformation

the process of HME reducing drugs into metabolites