neuroscience exam 2 flashcards

classical neurotransmitters (3 types + characteristics)

-acetylcholine

-monoamines: catecholamines→ dopamine, norepinephrine and epinephrine & indolamines→ serotonin

-amino acids: glutamate & GABA

-Released by the presynaptic vesicle in "quotas", synthesized in the terminal, and packed in vesicles

semi-classical neurotransmitters

peptides (small proteins). Only difference between classical and semi-classical is that the latter are synthesized in the soma

non-classical neurotransmitters (3 types + characteristics)

-lipids

-nucleosides

-soluble gasses

-Released by the postsynaptic cell, not released in quotas, not packed in vesicles. Still transmit info between neurons, so they are called neurotransmitters

Acetylcholine

classical neurotransmitter. Primary neurotransmitter secreted by axons of the PNS that terminate at muscle cells to control muscle contraction. Primary means by which postsynaptic action of acetylcholine is terminated is by enzymatic degradation.

Botulinum toxin

acetylcholine antagonist, prevents release by terminal buttons (can result in paralyzation). ACh is loaded into vesicles by the vesicle ACh transporter, where it is stored until being released from the presynaptic cell.

synthesis of acetylcholine

Acetylcholine is composed of choline and acetyl coenzyme A. The enzyme choline acetyltransferase (ChAT) is required to produce ACh from the precursors. After being released by the terminal button, ACh is deactivated by the enzyme acetylcholinesterase (AChE), which is present in the postsynaptic membrane. AChE breaks down one molecule of ACh into its two precursors

acetylcholine and its different locations

-dorsolateral pons→ REM sleep

-basal forebrain→ activating cortex, perceptual learning

-medial septum→ electrical rhythms of the hippocampus and modulate its functions

Black widow spider venom

poison that triggers the release of acetylcholine until there is no more acetylcholine to be released anymore

Myasthenia gravis

weakening of neuromuscular function. autoimmune disorder in which an antibody is made for acetylcholine receptors, which makes it hard for acetylcholine to attach. Solution is a drug that increases acetylcholine so that it has more chances to attach

Neostigmine

drug that inhibits activity of acetylcholinesterase so that acetylcholine stays in cleft for a longer time (therefore it has more chances to attach)

acetylcholine receptors (2)

-Nicotinic receptor: ionotropic receptor that is stimulated by nicotine & blocked by curare

-Muscarinic receptor: metabotropic receptor that is stimulated by muscarine and blocked by atropine

monoamines

indoleamines and catecholamines

indolamines

class of amines that includes serotonin

Catecholamines

class of amines that includes dopamine, norepinephrine and epinephrine

synthesis of catecholamines

The precursor molecule is modified slightly, step by step, until it achieves its final shape. Each step is controlled by a different enzyme, which causes a small part of the molecule to be added or taken off

synthesis of catecholamines: tyrosine

Rate limiting enzyme. Activation is associated with phosphorylation which speeds activity. Precursor of dopamine and norepinephrine. Modified by tyrosine hydroxylase and becomes L-Dopa

synthesis of catecholamines: L-Dopa

Precursor. Modified through the activity of the enzyme DOPA decarboxylase and becomes dopamine. Often used to treat Parkinson's disease because of its effect as a dopamine agonist

synthesis of catecholamines: Dopamine β-hydroxylase

converts dopamine to norepinephrine. Only neurons that release norepinephrine contain dopamine β-hydroxylase; however, both dopamine- and norepinephrine-releasing neurons contain tyrosine hydroxylase

dopamine

classical neurotransmitter. concentrated within the vesicles and bound to the inner membrane, released along with the neurotransmitters. produces both excitatory and inhibitory postsynaptic potentials, depending on the postsynaptic receptor

dopamine pathways

-mesocortical system

-mesolimbic system

-nigrostriatal system

-tuberoinfundibular pathway

-thalamus dopamine system

Mesocortical system

system of dopaminergic neurons originating in the ventral tegmental area and terminating in the prefrontal cortex. These neurons have an excitatory effect on the frontal cortex and affect functions such forming short-term memories, planning, and problem-solving

Mesolimbic system

system of dopaminergic neurons originating in the ventral tegmental area and terminating in the nucleus accumbens, amygdala and hippo campus. The nucleus accumbens plays an important role in the reinforcing (rewarding) effects of certain categories of stimuli, including those of drugs that people abuse.

Nigrostriatal system

A system of neurons originating in the substantia nigra (part of the brain related to movement) and terminating in the neostriatum (caudate nucleus and putamen). The neostriatum is an important part of the basal ganglia, which is involved in the control of movement

parkinson's disease

neurological disease characterized by tremors, rigidity of the limbs, poor balance, and difficulty initiating movements, caused by degeneration of the nigrostriatal system.

Tuberoinfundibular pathway

connects the population of dopamine neurons in the arcuate nucleus of the mediobasal hypothalamus (the 'tuberal region') to the median eminence (the 'infundibular region'). Regulates the secretion of prolactin from the anterior pituitary gland.

Thalamus dopamine system

Connect the PAG, ventral mesencephalon, hypothalamic nuclei, lateral parabrachial nucleus to the thalamus. Thalamus filters sensory info, and it has been found that glutamate and dopamine are involved in this process

dopamine receptors

5 types of receptors that are all G-protein coupled metabotropic receptors, and can be excitatory or inhibitory to the postsynaptic neuron. Categorized into 2 main subtypes: D1-like and D2-like

D1-like

-Activation is coupled to increases in cAMP and is typically excitatory. They are coupled to Gs.

-D1

-D5

D2-like

-activation reduces cAMP and is typically inhibitory. They are coupled to Gi/o.

-D2:

-D2Sh: short version. presynaptic autoreceptor, they regulates synthesis, storage and release of dopamine into the synaptic cleft

-D2Lh: long version of D2, may have the classic function of a postsynaptic receptor

-D3

-D4

drugs related to dopamine (4)

apomorphine, chlorpromazine, cocaine, amphetamine

Apomorphine

D2 agonist. blocks dopamine autoreceptors at low doses. At higher doses it blocks postsynaptic receptors as well.

Chlorpromazine

reduces the symptoms of schizophrenia by blocking dopamine D2 receptors associated with hallucination and psychosis

Cocaine and Methylphenidate (Ritalin)

Inhibits the reuptake of dopamine. Helps those with ADHD who have lower than optimum levels of dopamine

Amphetamine

Release dopamine and norepinephrine ( most transporters don't differentiate between the two) & cause the transporter to run in reverse

Norepinephrine

classical neurotransmitter. neuroandrogenic, usually in autonomic NS. The cell bodies of the most important noradrenergic system begin in the locus coeruleus, a nucleus located in the dorsal pons

norepinephrine receptors (3)

-Beta 1: excitatory, Gs

-Alpha 1: excitatory, postsynaptic terminal, Gq

-Alpha 2: inhibitory, autoreceptor, Gi

PNMT

enzyme found primarily in the adrenal medulla that converts norepinephrine (noradrenaline) to epinephrine

epinephrine

classical neurotransmitter. androgenic, found in small group of neurons in brainstem, activity regulated by corticosteroids

AMPT

blocks the activity of tyrosine hydroxylase and thus interferes with the synthesis of catecholamines

Reserpine

interferes with storage of monoamines in synaptic vesicles. If monoamines can't move into vesicles they are either not released or destroyed

Fusaric acid

inhibits activity of enzyme dopamine-ßhydroxylase and thus the production of norepinephrine without affecting the production of dopamine

inactivation of catecholamines (2)

MAO and COMT

Monoamine oxidase (MAO, 2)

-intra-cellular, located in the outer membrane of the mitochondria., play a role in inactivating catecholamines that are free within the nerve terminals and not protected by storage vesicles

-MAO-A: very selective for NE and serotonin

-Moclobemide: blocks the activity of MAO-A, increase noradrenergic tone

-MAO-B: Dopamine. acts on a broad spectrum of phenylethylamines. severe hypertensive crises after ingestion of food containing large amount of tyramine (port wine, cheese, herrings)

-Deprenyl: block activity of MAO-B, increase dopaminergic tone

Catechol-O-methyltransferase (COMT)

found in nearly all cells, acts on extraneuronal catecholamines

Serotonin (5HT)

classical indoleamine neurotransmitter, also called 5-hydroxytryptamine. It exists in different locations around the body, which is why it is known by several different names. involved in mood and pain regulation, and the control of eating, sleep, arousal, and dreaming.

synthesis of serotonin

structure primarily responsible for the production of serotonin is the raphe nuclei. The precursor for serotonin is the amino acid tryptophan. The enzyme tryptophan hydroxylase acts on tryptophan, producing 5-HTP (5-hydroxytryptophan). The enzyme 5-HTP decarboxylase converts 5-HTP to 5-HT (serotonin).

PCPA

drug that inhibits the activity of tryptophan hydroxylase and thus interferes with the synthesis of 5-HT

serotonin receptors (6)

5HT1A, 5HT1B, 5HT1D, 5HT1A-2C, 5HT4, 5HT3

5HT1A

Autoreceptor on dendrites and soma. inhibition of adenylyl cyclase (postsynaptic, Gi)

5HT1B and 5HT1D

Presynaptic autoreceptor, inhibition of adenylyl cyclase (Gi)

5HT2A-2C

Stimulation of phosphoinositide-specific phospholipase C (Gq). Related to the subjective feelings of anxiety & sleep

5HT4

Stimulation of adenylyl cyclase (Gs)

5HT3

Ionophoric. No G protein coupled to it. Related to appetite and eating disorders. Located in the hypothalamus and guts

drugs related to serotonin (4)

-fluoxetine/prozac

-fenfluramine

-lsd

-mdma

Fluoxetine (Prozac)

inhibits the reuptake of 5-HT. Used to treat Depression/OCD

Fenfluramine

stimulates the release of 5-HT. Appetite suppressant used to treat obesity

LSD

stimulates 5HT2A receptors

MDMA ("ecstasy")

Cause the transporter for serotonin to run in reverse (release serotonin) leading to a hallucinogenic effect. Also cause the transporter for norepinephrine to run in reverse (release norepinephrine) leading to an excitatory effect

glutamate

classical neurotransmitter, amino acid. main excitatory neurotransmitter in the brain and spinal cord. Synthesized from glutamine by the enzyme glutaminase in one step. After synthesization, it is stored in vesicles in the presynaptic neurons, from where it's released after an action potential

ionitropic glutamate receptors (3+ cotransmitters)

-NMDA

- glycine, L- and D-serine

-AMPA

-Kainate

NMDA

specialized ionotropic glutamate receptor that controls a calcium channel that is normally blocked by Mg+ ions (Mg+ dissociates from the membrane when it is depolarized); has several other binding sites. Voltage dependent. Calcium serves as a second messenger, binding with—and activating—various enzymes within the cell. One important result of this second messenger system is an alteration in the characteristics of the synapse that provide one of the building blocks of a newly formed memory

Glycine

comes from glial cells. leads to a lot more activation of the receptor

L- and D-serine

L-serine is consumed in the diet and D-serine is made in the body from L-serine. The body uses D- and L-serine to make proteins. D-serine also sends chemical signals in the brain. This might help with schizophrenia and other brain conditions.

AMPA

An ionotropic glutamate receptor that controls a sodium channel. It is stimulated by AMPA and when glutamate attaches to a binding site, it produces EPSP. Fastest response, most common glutamate receptor, and most times it is not voltage dependent

kainate

ionotropic glutamate receptor that controls a sodium channel; stimulated by kainic acid

Metabotropic glutamate receptors

mGluRs. 8 different types, divided into group I, II, and III based on similarity, pharmacology and intracellular signaling mechanisms

drugs related to glutamate (2)

-AP5

-PCP

AP5 (2-amino-5-phosphonopentanoate)

A drug that blocks the glutamate binding site on NMDA receptors.

PCP

Phencyclidine; a drug that binds with the PCP binding site of the NMDA receptor and serves as an indirect antagonist (when it attaches to its binding site, calcium ions cannot pass through the ion channel)

GABA

amino acid, classical neurotransmitter. Inhibitory neurotransmitter with widespread distribution throughout the brain and spinal cord. Produced from glutamic acid by the action of an enzyme (glutamic acid decarboxylase, or GAD).

GABA receptors

-Divided into 3 classes: GABAa, GABAb and GABAc

-GABAa, GABAc: GABA-gated chloride ion-conducting channels. Varieties of GABAa are found all over the CNS, and GABAc receptors are primarily found in the retina

-GABAb: G-protein coupled receptors. Inhibitory, metabotropic autoreceptor

drugs related to GABA (2)

-benzodiazepine

-alcohol

Benzodiazepine

anxiolytics, or "anxiety-dissolving" drugs, and are used to reduce symptoms of anxiety, reduce seizure activity, and produce muscle relaxation

alcohol

Indirect GABA receptor agonist (among other mechanisms). Effects are sedation, memory impairment, muscle relaxation

neuropeptides

semi-classical neurotransmitter. small proteins produced by neurons that act on G protein-coupled receptors and are responsible for slow-onset, long-lasting modulation of synaptic transmission

endogenous opioid

class of peptides secreted by the brain that act as opiates. Reduce pain because they have direct effects on the brain through their actions in the endogenous opioid system.

Naloxone

blocks opiate receptors

lipids

non-classical neurotransmitter. retrograde. Lipid neurotransmitters appear to be synthesized on demand; that is, they are produced and released as needed and are not stored in synaptic vesicles.

Endocannabinoid

lipid, endogenous ligand for the cannabinoid receptors, which also binds with THC, the active ingredient of marijuana

Anandime

first cannabinoid to be discover and probably the most important one

THC

active ingredient in marijuana; activates CB1 receptors in the brain

Nucleosides

non-classical neurotransmitter. a compound (e.g., adenosine or cytidine) commonly found in DNA or RNA

Adenosine

combination of ribose and adenine; serves as a neuromodulator in the brain

caffeine

blocks adenosine receptors, thus more norepinephrine is released

soluble gasses

non-classical neurotransmitter. retrograde. Nitric oxide and nitric oxide synthase

Nitric oxide

gas produced by cells in the nervous system; used as a means of communication between cells. non-classical neurotransmitter

How do indoleamines and catecholamines differ?

Catecholamines (dopamine, norepinephrine and epinephrine) are synthesized from tyrosine. Indolamines (serotonin and tryptamine) are synthesized from tryptophan

What is a rate limiting enzyme?

enzyme of which the activity determines the overall rate of a metabolic pathway

What disease is MPTP made to model?

Parkinson's disease

Why would you take beta blockers?

Beta blockers block the release of the stress hormones adrenaline and noradrenaline. They are widely prescribed for angina, heart failure and some heart rhythm disorders, and to control blood pressure.

Experimental ablation

removal or destruction of a portion of the brain of a laboratory animal; presumably, the functions that can no longer be performed are the ones the region previously controlled

Excitotoxic lesion

brain lesion produced by intracerebral injection of an excitatory amino acid, such as kainic acid. The amino acid kills neurons by stimulating them to death

6HD

chemical that is selectively taken up by axons and terminal buttons of noradrenergic or dopaminergic neurons and acts as a poison, damaging or killing them. The chemical destroys neural cell bodies in the vicinity but spares axons that belong to different neurons that happen to pass nearby. This selectivity permits the investigator to determine whether the behavioral effects of destroying a particular brain structure are caused by the death of neurons located there or by the destruction of axons that pass nearby

Stereotaxic surgery

Brain surgery using a stereotaxic apparatus to position an electrode or cannula in a specified position of the brain. Uses an atlas (collection of drawings of sections of the brain with measurements that provide coordinates for stereotaxic surgery made in relation to the bregma/front of head) and apparatus (includes a head holder, a holder for an electrode or cannula, and a calibrated mechanism that moves the electrode/cannula holder in measured distances)

histological methods

methods of fixing tissue, slicing tissue, and staining. Done after producing a brain lesion and observing its effects on an animal's behavior so that researchers can observe the brain under the microscope and see the location of the lesion

fixative

A chemical such as formalin; used to prepare and preserve body tissue. It protects the brain from autolytic (self dissolving) enzymes that break down tissue and decomposition by bacteria or molds. Fixatives cross-link proteins to strengthen the very soft and fragile brain tissue and kill any microorganisms that might destroy it. Fixative might not get inside the brain fast enough, so then it might start to rot. To prevent this, we do perfusion

perfusion

process by which an animal's blood is replaced by fluid (dilute saline solution and then dilute fixative solution) in preparing the brain for histological examination. Gets rid of the protein in the blood

Microtome

instrument that produces very thin slices of tissues. Contains a knife, a platform on which to mount the tissue, and a mechanism that advances the knife (or the platform) the correct distance after each slice so that another section can be cut. In most cases, the platform includes an attachment that freezes the brain to make it hard enough to be cut into thin sections

Immunocytochemical methods

neurochemical histological method that uses radioactive antibodies or antibodies bound with a dye molecule to indicate the presence of particular proteins or peptides. antibodies attach themselves to their antigen. When the investigator examines the slices with a microscope (under light of a particular wavelength in the case of fluorescent dyes), they can see which parts of the brain—even which individual neurons—contain the antigen.Sometimes we want to know about functional proteins, certain receptors, etc. we use this method for that. Used for tracing efferent axons

in situ hybridization

when we want to evaluate a level of protein/ expression of RNA. more RNA means that we have more protein, thus more function. Generally talking this correlation does exist, but it is not always true. You are not measuring the protein itself. The production of radioactive RNA complementary to a particular messenger RNA in order to detect the presence of the messenger RNA.