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Neurology Exam 1
Neurology Exam 1 TTUHSC
177
Physiology
Professional
08/13/2013

Additional Physiology Flashcards

 


 

Cards

Term
Name the 6 chemical transporters.
Definition

 

oAcetylcholine (ACh)

 

oDopamine (DA)

 

oNorepinephrine (NE)

 

oSerotonin (5-HT)

 

oGlutamate

 

oγ-Aminobutyric acid (GABA)

 

Term
Name the 4 types of neurotransmitters and give their examples.
Definition

 

oAmino acids - derived ex. 5-HT and GABA

 

oCtecholaminesex. Norepinephrine, Dopamine and Epinephrine.

 

oOther small molecules ex. Nitric oxide and prostaglandins.

 

oNeuropeptides ex. peptide Y

 

Term
How are dopamine, norepinephrine, GABA, acetylcholine and peptides removed from the synaptic cleft?
Definition

Norepinephrine, dopamine and GABA are removed via reuptake

 

Acetylcholine and peptide Y removed via metabolism

 

Glutamate removed via reuptake via glial cells.

Term
Give drug targets for neurotransmission process.
Definition

 

Neurotransmitter synthesis

 

Depolarization-induced exocytosis

 

Neurotransmitter-receptor binding

 

Vesicular uptake and storage

 

Termination of neurotransmitter action (inhibition of enyzmes)

 

Term
4 chemical and physical properties that that contribute to drug binding to a specific receptor.
Definition

 

Hydrophobicity
pKa (ionization state)
conformation
spatial arrangement of atoms

 

Term

 

oImportant in CNS, peripheral NS, heart, neuromuscular junction

 

oResponsible for fast synaptic transmission

 

Definition

 

Ligand-gated ion channels (ionotropic receptors)

 

Term

Describe the ligand-gated ion channels (ionotropic receptors)

 

Definition

 

oRelease of NT causes electrical effect on postsynaptic neuron by opening a specific ion channel => change in membrane potential

 

Term
Give examples of ligand-gated ion channels
Definition

 

oComplex proteins, 4-5 subunits

 

Examples: nicotinic cholinergic rec., GABA receptors

 

 

 

Term
Describe G-protein coupled (metabotropic) receptors

 

Definition

 

oSingle subunit with 7 trans-membrane spanning domains
oInduce conformational change activating G-protein family to regulate signaling pathways
oExamples: most of serotonin receptors

 

Term
Name the 4 types of neurotransmission receptors
Definition

Ligand-gated ion channel (ionotropic) receptors

 

G-protein coupled (metabotropic) receptors

 

Receptor tyrosine kinase

 

Nuclear hormone receptor

Term
Which neurotransmission receptor has allosteric binding site?
Definition
Ligand-gated ion (ionotropic) receptor
Term
Describe glutamate
Definition

Synthesized in the neurons by glial cells and metabolized to glutamate in presynaptic terminals (and transamination of alpha-ketoglutarate)

 

Does not cross blood-brain barrier

 

 

 

trivia: glutamate is found in chinese food and was used by the Romans to sweeten food. Can cause  hypotension

Term
what is the function of glutamate?
Definition

 

Glutamate is a classical fast excitatory neurotransmitter

 

Very high concentration and widespread in the brain

 

Increased levels are neurotoxic

 

oExcitotocixity: ability of glutamate to destroy neurons by prolonged excitatory action

 

oExcitotoxicity is implicated in many diseases, including stroke, trauma, neurodegenerative disorders, hyperalgesia, epilepsy

 

Term
describe the excitotoxicity of glutamate
Definition

 

oExcitotocixity: ability of glutamate to destroy neurons by prolonged excitatory action

 

oExcitotoxicity is implicated in many diseases, including stroke, trauma, neurodegenerative disorders, hyperalgesia, epilepsy

 

Term
Name the 2 subtypes of glutamate receptors
Definition

 

Ionotropic glutamate receptors:

 

oNon-NMDA receptors mediate fast depolarization

 

Cation channel (predominately Na+ and K+)

 

AMPA – most prevalent

 

Kainate

 

oNMDA (N-methyl-D-aspartate) receptors

 

Permeable to Na+, K+, and Ca++ ions

 

Role in learning, memory

 

Metabotropic (GPCR) glutamate receptors

 

omGluR 1-8; sub-groups depending upon 2nd messengers

 

Term

_____ receptors are target for antagonist drugs in development for anxiety, schizophrenia, pain, epilepsy

 

Definition
Metabotropic glutamate
Term
What does GABA stand for?
Definition
Gamma-aminobutyric Acid (GABA)
Term
T/F: Glutamate is synthesized from GABA
Definition
False - GABA is synthesized from glutamate
Term
__ is the main inhibitory neurotransmitter in the brain
Definition

gamma-aminobutyric acid (GABA)

 

oMay be responsible for mediation of presynaptic inhibition in spinal cord

Term
Effects of lack of GABA neurons is...?
Definition
Neurons fire too often and too easily (lacks inhibitory effects of GABA)
Term
Give examples of GABA deficiency
Definition
Anxiety disorders, seizures, panic attacks, Parkinson’s  syndrome
Term

Give the 3 GABA receptors.

 

a. which is one is metabotropic (GPCR)?

b. Which is ones have allosteric modulators?

c. which one is expressed mostly in brain and retina?

d. name the one that uses inotropic (ligand-gated Cl- channel) receptors

 

Definition

Metabotropic (GPCR) = GABA-B receptor



GABA-A = allosteric modulators ex. barbiturates, BZD

 

Expressed in brain and retina = GABA-C

 

GABA-A and GABA- C receptor = ionotropic ligand-gated Cl- channel) receptors

 

 

Term
Give the difference between metabotropic and ionotropic receptors.
Definition

Metabotropic acts via secondary messengers.


Ionotropic receptors form an ion channel pore. In contrast, metabotropic receptors are indirectly linked with ion channels on the plasma membrane of the cell through signal transduction mechanisms, oftenG proteins. Hence, G protein-coupled receptors are inherently metabotropic. Other examples of metabotropic receptors include tyrosine kinases orguanylyl cyclase receptors

Term
Give the antagonists and agonist agents for GABA-A, GABA-B, and GABA-C receptors.
Definition

GABA-A = Flumazenil

GABA-B = Baclofen

 GABA-C = none

Term
oagonist agent that is useful in muscular spasticity
Definition
Baclofen- GABA-B receptor agonist
Term

Give examples of GABA-A receptor agents. Which are agonist, antagonists or positive allosteric modulators?

 

Definition

Agonist - Muscimol

Antagonists - Picrotoxin & Flumazenil

Positive allosteric modulators - Benzodiazepines, barbiturates, general anesthetics, neurosteroids, & alcohol.

Term
Describe the synthesis of acetylcholine
Definition
Synthesized from acetyl CoA and choline in the nerve terminal (enzyme: choline acetyltransferase)
Term
Describe the activity of acetylcholine.
Definition
Acts on nicotinic acid muscarinic receptors and cause excitatory or inhibitory effects.
Term
Describe the elimination process of acetylcholine.
Definition
metabolized by cholinesterase enzymes (acetylcholinesterase and butyrylcholinesterase) in the synaptic cleft.
Term
Name and describe the 2 cholinergic receptors
Definition

ACh can have excitatory or inhibitory action

 

Nicotinic receptors (ionotropic) - Excitatory action --> 2 types (muscle and neuronal)

 

 

Muscarinic receptor (metabotropic) --> Excitatory (M1, M3, & M5) and inhibitory (M2 & M4) => found in autonomic nervous system (parasympathetic), smooth muscle, heart, CNS, and eye.

Term
describe 3 differences between nicotinic and muscarinic cholinergic receptors.
Definition
  1. Nicotinic receptors are excitatory, while muscarinic receptors are both excitatory and inhibitory.
  2. Nicotinic cholinergic receptor is found in skeletal muscles at neuromuscular junctions, autonomic ganglia and CNS, while muscarinic receptors are found in smooth muscles, autonomic nervous system (parasymp), heart, CNS, and eye.

 

 

Term
Cholinergic drug of abuse is ___
Definition
nicotine
Term
Alzheimers disease are treated with ____, while Parkinson's disease is treated with ___
Definition

Alzheimers = cholinesterase inhibitors (pro-cholinergic)

 

Parkinson's = anti-cholinergic agent (anti-muscarinic agents)

 

 

Note: Never give a Parkinson's patient a cholinesterase inhibitor or vice-versa.

Term
____ are used as muscle relaxants during general anaesthesia

 

Definition
Antinicotinic drugs
Term

 

____ is a cholinergic agent used for motion sickness

 

Definition
scopolamine (M1 antagonist)
Term
Name the 3 catecholamines
Definition

Dopamine

Norepinephrine

Epinephrine

Term
What is the main location and effects of norepinephrine
Definition

Location: most brain regions especially hypothalamus and some parts of limbic system.

 

 

Actions: inhibitory effects via beta receptors and sometime excitatory via alpha or beta receptors

Term
Give 3 functions of norepinephrine
Definition

 

oArousal (wakefulness, alertness)

 

oBlood pressure regulation (central and peripheral synapses)

 

oControl of mood (implicated in depressive disorders)

 

Term

Action of NE is terminated by ____ and _____ inside the cells 

 

Definition

re-uptake into noradrenergic nerve ending

and


circulating NE is degraded enzymatically by
COMT and MAO

Term
Give the types of nicotinic adrenergic receptors
Definition
None -all adrenergic receptors are metabotropic
Term
Give the 3 types of metabotropic adrenergic receptors and their functions
Definition

alpha 1 - neurons - vasoconstriction, relaxation of GI muscles, and contraction of genitourinary smooth muscles.

 

alpha 2 - glial and vascular cell ==> controls release of NE; activates platelet aggregation, inhibition of NT release, and contraction of muscle.

 

beta - beta 1, 2, 3

beta-1 => increase cardiac rate and force

beta-2 => bronchodilation and smooth muscle dilation; insulin release

beta-3 => lipolysis

Term
Which adrenergic receptor is responsible for lipolysis?
Definition
beta 3
Term
Clinical uses of α-adrenoreceptor’santagonists
Definition

 

oSevere hypertension (α1-selective antagonist eg. doxazosin)
oBenign prostatic hypertrophy (α1-selective antagonist eg. tamsulosin)
oPhaeochromocytoma(irreversible nonselective α-antagonist phenoxybenzamine)
Term
Clinical uses of β-adrenoreceptor’santagonists
Definition

 

oCardiovascular:

 

Angina pectoris, myocardial infarction, dysrhythmias, heart failure, hypertension

 

oOther:

 

Glaucoma, thyrotoxicosis, anxiety, migraine prophylaxis, benign essential tremor

 

Term
Give example of alpha-1 and 2 adrenoreceptor agonists and what they are used for.
Definition
oPhenylephrine and Oxymetazoline - Selective  α1-agonists are used for symptomatic relief in nasal congestion.

 

o Clonidine - α2-agonists are used for BP lowering ( acts on presynaptic α2 receptors)

 

Term
Give example and clinical uses of β-adrenoreceptor’sagonists 
Definition

 Salmeterol and albuterol - β2-selective agents are used in the treatment of asthma.

 

Term
Give examples of NE reuptake inhibitors
Definition
tricyclic antidepressants, cocaine
Term
Drugs affecting NE synthesis
Definition

Carbidopa, methyldopa (used occasionally for phaeochromocytoma)

 

Term
Drugs affecting NE release & storage
Definition
Reserpine (peviously used for hypertension)
Term

 

Drugs inhibiting catecholamine metabolism

 

Definition

 

Monoamine oxidase inhibitors (MAOIs)

 

Term
This NT is involved in Parkinson’s disease, schizophrenia, attention deficit disorder, drug dependence, certain endocrine disorders
Definition
Dopamine
Term

 

Dopamine is most abundant in ____

 

Definition
corpus striatum
Term

 

Dopamine is metabolized by ___ and ____

 

Definition
MAO and COMT
Term

Which dopaminergic pathway is the most important for motor control?

 

 

A.Tuberohypophyseal system

 

B. Mesolimbic/mesocortical pathway

 

C. Nigrostriatal pathway

 

Definition
C - Nigrostriatal pathway (75% of dopamine in brain)
Term
Dopamine receptors are ____ in nature (nicotinic or metabotropic?)
Definition
Metabotropic
Term
Name and describe the excitatory and inhibitory dopamine receptors.
Definition

excitatory - D1& D5 like receptors => activates adenyl cyclase

 

 

Inhibitory - D2, D3 & D4 receptors => inhibits adenyl cyclase  suppress Ca2+ and activates K+ channels

Term

____ disease is associated with dopamine deficit in the nigrostriatal pathway

 

Definition
Parkinson‘s
Term

What is the endocrine effects of dopamine.

 

Definition
inhibits release of prolactin
Term
Main behavioral effects of dopamine.
Definition

DI receptor:

 

oActivity, pleasure, addiction

 

Limbic system and ventral                                                             tegmental area

 

oCorrect thinking

 

Cortical forebrain

 

Term
What type of dopaminergic agent is preferred in treatment of Parkinson's disease? (agonist or antagonist?)
Definition
Dopamine agonists
Term
Give examples of some pro-dopaminergic agents.
Definition

 

oDopamine precursors (Levodopa)

 

oDopamine receptors agonists (bromocriptine, pergolide)

 

oMAO-B inhibitors (selegiline / rasagiline)

 

Term
Dopamine is synthesized from ___ in the ___
Definition
Tyrosine in the corpus striatum
Term
Dopamine, like norepinephrine, is metabolized by ____
Definition
MAO and COMT
Term
How is dopamine used to treat psychotic disease like schizophrenia?
Definition
Dopamine receptor blockers have antipsychotic effects (D2 blockers)
Term

 

Serotonin is synthesized from the ____

 

Definition
amino acid tryptophan
Term

 

Serotonin receptors are found in the ___and the ____

 

Definition
brain and
GI tract
Term

Most serotonin receptors are ____, only 5-HT3 is a ____

 

Definition

G-protein coupled



ligand-gated ion channel

Term

 

Serotonin is Metabolized by ____

 

Definition
MAO
Term
Important effects of serotonin
Definition

 

oHallucinations and behavioral changes

 

Many hallucinogens are 5-HT2A agonists (LSD)

 

Many antipsychotic drugs are 5-HT2A antagonists

 

oSleep, wakefulness, and mood

 

Depletion of 5-HT eradicates sleep

 

Many 5-HT receptor agents used as antidepressant drugs

 

oFeeding behavior

 

5-HT1A agonists and 5-HT2 antagonists increase appetite

 

Inhibition of 5-HT reuptake causes loss of appetite

 

oControl of sensory transmission (pain pathways)

 

5-HT has an inhibitory effect on pain transmission

 

Term

5HT1 B/D agonists are used for _____

 

5HT2 antagonists are used for _____

 

Selective serotonin reuptake inhibitors (SSRIs) are used for _____

 

5HT3 antagonists are used for _____

Definition

 

5-HT1B/D agonists (triptans) = Used for migraine treatment

 

5-HT2 antagonists (ketanserin) = Used in migraine prophylaxis

 

Selective serotonin reuptake inhibitors (SSRIs) = Antidepressant drugs

 

5-HT3 antagonist (ondansetron)= Used for the treatment of chemotherapy induced nausea and vomiting

 

Term
The function of nervous system is to ____
Definition
regulate the functions of other tissues and organs in the body in order to maintain homeostasis and optimize function
Term
Difference between neurological and pyschiatric disorders.
Definition
neurological disorders are characterized by physical manifestations (e.g., motor dysfunction) whereas psychiatric disorders are more internal disorders, that is, disruptions of mental processes.
Term
Describe the 3 types of nervous system structure and function.
Definition

Central Nervous System (CNS);  Brain and spinal cord

 

Peripheral Nervous System (PNS):  Sensory neurons, Voluntary motor systems, Autonomic systems


Enteric Nervous System (ENS): Neuroendocrine cells in the GI tract and related viscera that regulate their function.

 

 

Term
Nervous tissue is highly metabolic and oxidative, requiring constant supply of ___  and ____ to function.
Definition
glucose and O2
Term
Brain has limited anaerobic capacity and very low levels of _____
Definition
glycogen
Term

Metabolic demands are higher in ____matter than in ___matter.  This is reflected in increase (~4-fold) density of capillaries in ___matter.

 

 

Definition

gray > white matter


gray 

Term

Neurons may be classified according to 6 factors : t

Definition

1.  Neurotransmitter they release


2. Morphology of neuron (size & shape- examples pyramidal, stellate, bipolar, chandelier cells


3. Location in the brain


4. Function 

Term
Most neurons are _____, which means when the neuron dies, there is no cell to replace it. This is a critical factor in CNS disorders.  
Definition
post-mitotic
Term

There are a few neuronal populations that are constantly produced; most important are __and ___.

Definition
olfactory neurons and hippocampal dentate gyrus neurons. 
Term

These are a type of glial cell that supports the function of neurons. They help maintain the ionic composition of the brain ECF, supply metabolites to neurons and enhance blood-brain barrier function of blood vessels. During neuronal degeneration, they become reactive and are involved in clearing cellular debris and sealing off damaged regions by creating a glial scar.  There are approximately 10x as many them in human brain as there are neurons. 

Definition
astrocytes 
Term
These cells are responsible for myelination of axons and predominate in white matter. 
Definition
Oligodendrocytes
Term

Myelination of axons in the PNS is accomplished by ____.

Definition
Schwann cells
Term

These are bone marrow derived cells that invade the CNS early in development. They are the “macrophages of the CNS”. They phagocytize debris and cellular content released during normal activity. They are also critical for synaptogenesis in that they help remodel tissue structure to allow for expansion of synapses or alternatively elimination of unnecessary synapses. During tissue damage they also become reactive and contribute clearing dead and damaged tissue.

Definition
Microglia
Term

These cells form a layer that lines the ventricles and the surface of the brain. They contain cilia that help propel the movement of CSF.

Definition
Ependymal cells
Term

They are responsible for CSF production and along with BBB capillaries help determine the composition of brain ECF. Found in choroid plexus.

Definition
Epithelial cells
Term
Makes up the blood vessels of the brain.
Definition
endothelial cells
Term
CSF  composition approximately equal to plasma
Definition
Na+, Cl-, bicarbonate
 osmolarity
Term
CSF  composition less than plasma
Definition

K+, Ca++ ,glucose

Term

Which of these are elevated in plasma and which are negligible?

 

K+

Ca2+

Creatinine

Mg2+

Cholesterol

Proteins

glucose

Definition

Elevated in CSF = Mg2+ anmd creatinine

 

Neglible = protein and cholesterol

Term
The extracellular fluid composition is tightly regulated by __and __
Definition
blood-brain barrier and choroid plexus. 
Term
T/F: Brain capillaries are not fenestrated
Definition
True
Term
Brain capillaries contain ____that block paracellular flow and do not readily engage in transcellular pinocytosis. Thus, in order for hydrophilic molecules to enter the brain, there must be specific transport proteins for the molecules. 
Definition
tight junctions 
Term
Transporters for ___, ___ and ____ are present in BBB cells or choroid plexus and are critical for brain development and normal function.
Definition
 glucose, amino acids and vitamins 
Term
There are no brain transporters for ___ and ____ amino acids at the BBB.
Definition
Glutamate and Aspartate 
Term

So where does the Glu in brain come from? 

Definition
Alpha-ketoglutarate in the TCA is transaminated to make Glu (and GABA) for neurotransmission. The a-ketoglutarate comes from glucose by glycolysis and TCA; hence the constant need in brain for glucose (not just ATP).
Term
T/F: The CNS has many primary or secondary lymphoid tissue.
Definition
False - The CNS is devoid of any primary or secondary lymphoid tissue.
Term
CNS tissue does not normally express Class____antigens. However, immune activity can occur in the CNS
Definition
 II 
Term
In pathological conditions such as ____, the BBB may be compromised with infiltration of blood macrophages and neutrophils.
Definition
stroke or epilepsy
Term
Afferent (posterior) of brain is responsible for ___, while the efferent (anterior) is responsible for _____.
Definition

Afferent (posterior) = processing signals

efferent (anterior) = producing response 

 

Term
Changes in the strength of synapses are referred to as _____.
Definition
synaptic plasticity
Term
At rest the neuronal membrane is impermeable to ___and slightly leaky to ___
Definition
Na+ ; K+
Term
T/F: All neurons have a resting membrane of -70mV.
Definition
False: different neurons have different resting membrane potentials and this is important for the physiological function of the cell.
Term

T/F:

 

Na+ = depolarization (-40mV)

K+ = repolarization

Definition
True
Term

The rate at which an action potential propagates down an axon is due to two factors:

Definition

1.     The diameter of the axon: current spreads faster due to lower electrical resistance.


     2. Myelination: Action potentials are conducted in a saltatory fashion where they skip myelinated sections of axon. Na+ channels are concentrated in unmyelinated membrane, the Nodes of Ranvier, where the action potentials are executed.

Term
Opening of ____channels leads to the influx of Na+ and depolarization and this is excitatory. Opening of ___channels causes influx of Cl- and hyperpolarization and this would be inhibitory.
Definition

cation = influx of Na+ = depolarization = excitatory


Anions = influx of Cl - = hyperpolarization = inhibitory

Term
T/F: Pre-synaptic potentials are graded potentials, unlike action potentials
Definition
False: Post-synaptic potentials are graded potentials, unlike action potentials
Term
The amount of depolarization/hyperpolarization is dependent on the amount of ___and ____
Definition
neurotransmitter  and the number of channels that open.
Term
The _____ and the____spread locally but degrade with distance from the ion channel
Definition

Excitatory Postsynaptic Potentials (EPSPs); 


 Inhibitory Postsynaptic Potentials (IPSPs

Term
How can Excitatory postsynaptic potentials generate action potential?
Definition

A single EPSP (typically only a few mV) is insufficient to trigger an action potential. So neuronal firing requires multiple EPSPs to reach threshold. The EPSPs may arise on different dendrites (termed spatial summation) from synapses formed by different upstream neurons. This is one mechanism by which neurons integrate incoming activity. 

Term
WHat is the difference between spatial and temporal summation?
Definition

Spatial summation: EPSP arises from different dendrites from synapses formed by different upstream neurons.

 

 

Temporal summations: EPSP received rapidly before membrane potential has been restored.

Term
Once membrane potential is reached, action potential is generated at the ____
Definition
Axon hillock
Term
By the combined processes of temporal and spatial summation, the ____integrates all the electrical information.
Definition
neuron 
Term
Neurotransmitter receptors are concentrated in these post-synaptic densities called ____.
Definition
Boutons
Term
What are passant synapses?
Definition
In some cases, neurotransmitters are released at ‘en passant’ synapses. These are dilations or varicosities in the axon where vesicles accumulate and secretion occurs. Neurotransmitters released from en passant synapses are more appropriately termed neuromodulators.
Term
Neurotransmitters released from en passant synapses are more appropriately termed _____.
Definition
neuromodulators
Term
Part of early human development involves “testing” of synapses for correct function. This occurs during certain periods if human development called ____
Definition
critical periods
Term
WHat is the difference between neurotransmitter and neuromodulators?
Definition
Neurotransmitters directly cause changes in membrane potential whereas neuromodulators increase or decrease the efficacy of other neurotransmitters without directly affecting membrane potential. 
Term

There are numerous other small metabolites that function as neurotransmitters. These include ___,___,__and ___ 

Definition
adenosine, nitric oxide, prostaglandins and cannabinoids, etc.
Term
Describe the Dale hypothesis and why it's no longer accepted.
Definition

The Dale Hypothesis (one neuron-one transmitter) is no longer accepted. Many neurons are capable of releasing multiple transmitters, although this is usually a major transmitter along with a peptide. Often a vesicle will contain both transmitters. I’ve never heard of Glu and GABA released by the same neuron or Norepi and 5HT released together.

Term
The brainstem is composed of the ___, ____, ___ and ____
Definition
medulla, the pons, the cerebellum and the midbrain.  
Term
What is the reticular formation?
Definition
The reticular formation is a collection of interconnected neuronal networks in the pons and midbrain that integrates sensory and motor information as well as higher order information from the cortex. It functions as an activating system to regulate alertness through interaction with the thalamus and cortex and to modulate the activity of extensor muscle tone (Danger, Will Robinson!)  The reticular formation modulates heart rate and blood pressure based on information received from chemoreceptors in the carotid sinus
Term

The _____also contains the location of the cell bodies for the catecholamines and serotonin.

Definition
brainstem 
Term
Major nuclei containing dopaminergic cells are located in the ___and _____
Definition

substantia nigra and the ventral tegmentum




substantia nigra = stratium = motor function


 ventral tegmentum = frontal cortex & limbic structures = motivation and behavior reinforcement

Term
The ____ is the most important noradrenergic nucleus.
Definition

 locus coeruleus


 Axons from LC project diffusely throughout nearly the entire brain.  NE fibers typically do not make classical synaptic structures but rather appear to release NE in a more hormonal or paracrine fashion from so-called "varicose" (beaded) structures in the axons.  NE appears to play a role in attention, arousal and vigilance.  The activity of LC neurons varies with the sleep-wake cycle.

Term
Serotonergic neurons are located primarily in the ___
Definition
raphe nuclei.  
Term
All sensory information with the exception of olfactory information proceeds to the ____ by first synapsing in the ___. 
Definition
cortex; thalamus
Term

    This region at the base of the brain functions to maintain the homeostatic environment of an organism. (For example, body temperature, appetite, reproductive hormones, emotional display)

Definition
Hypothalamus
Term
The ____applies emotional context to sensory information, that is, pleasant or unpleasant qualities to sensations
Definition
limbic system 
Term
this region of the brain is responsible for intellectual functioning
Definition
cerebral cortex
Term
The cerebral cortex is divided into two hemispheres that communicate via the ___
Definition
corpus callosum
Term
The cerebral cortex is divided into 4 major regions: 
Definition
Frontal, Parietal, Occipital and Temporal
Term
The ___ cortex is primarily efferent. The ____ regions are primarily involved in afferent functions.

Definition

frontal = efferent


parieto-temporal-occipto = afferent

Term
____cortex is where information first enters or leaves the cortex. 
Definition
Primary 
Term
Visual information from the lateral geniculate nucleus synapses first in the primary visual cortex at the _____
Definition
occipital pole of the brain.  
Term
Sensory information synapses at the somatosensory cortex in ____
Definition
the postcentral gyrus
Term

The motor cortex located on the precentral gyrus contains the neurons that synapse with motor neurons in the ventral horn of the ____

Definition
 spinal cord
Term

____cortex is where primary information is processed and is involved in higher (intellectual) functions


Definition
Association 
Term

visual information is broken down into where the object is and whether it’s moving in the magnocellular visual association cortical pathway in the _____cortex


Information regarding color and fine detail are analyzed in the parvocellular visual association pathwayin the _____cortex. 

Definition

parietal ;


temporal 



Term
  • The ____ association cortex is involved in interpreting the sensory information obtained from the surrounding primary cortical regions.
Definition
parieto-occipto-temporal
Term
The ____association cortex is involved in planning complex patterns and sequences of movements.  It is also responsible for carrying out prolonged thought processes and is involved in elaboration of thoughts.
Definition
prefrontal 
Term
The _____is responsible for the acquisition of new memories. However, the storage of those memories occurs throughout the ____. 
Definition

hippocampus ;

cerebral cortex

Term
2 ways to identify the function of a region of cortex
Definition

1) electrophysiology


2) lesion studies

Term
Electrodes placed on the surface of the scalp can record electrical activity occurring in the brain.  
Definition
Electroencephalography
Term
Under pathological conditions, epilepsy and some psychoses, changes may be seen using _____.
Definition
Electroencephalography
Term

____ is an imaging tool for structural analysis, rather than functional analysis of brain activity.

Definition
CT scanning
Term
______ is used to measure blood flow in various regions of the brain. The underlying principle is that increased neuronal activity leads to a local increase in blood flow to supply the metabolic demands of those neurons
Definition
Positron emission tomography
Term
_____ imaging tool is used to quantify receptor proteins of pharmacological agents in the brain
Definition
Positron Emission Tomography
Term
_____ imaging tool can detect subclinical infarcts in brain and to determine water content.
Definition
Magnetic Resonance Imaging (MRI) 
Term

___imaging technique is used to identify o    different phosphorylated intermediates, such as ATP and phosphocreatine, based on their chemical shift and thereby measure localized concentrations of these compounds.

 

Definition
MRI
Term
Used to monitor time-dependent blood flow to various regions of the brain.
Definition

Functional MRI

 

 

This technique relies on the ability of the instrument to distinguish between oxy- and deoxyhemoglobin and goes by the acronym BOLD. 

Term

Neurological disorders may be precipitated by all the usual suspects

Definition

·        Nutritional/Metabolic:  e.g, Thiamin deficiency- Wernicke-Korsakoff’s syndrome

·        Toxicity: e.g., heavy metal poisoning

·        Infectious: meningitis, neurosyphilis, AIDS-associated myopathy, dementia

·        Genetic: Gaucher’s disease, Adrenoleukodystrophy

·        Immunological:  Lambert-Eaton, Myasthenia gravis, Multiple sclerosis

·        Malignancy

·        Developmental

·        Trauma

 

·        Iatrogenic/drug-induced

Term

What does each disease occur (selective vulnerability):
 ALS

Parkinson's disease

Alzheimer's disease 

Definition

ALS - motor neurons

 

Parkinson's disease - dopaminergic neurons in substantia nigra

 

Alzheimer's disease - Association cortex (large pyramidal neurons)

Term
What is selective vulnerability?
Definition
Because the nervous system is functionally heterogeneous, disease processes will affect certain regions or certain cells and leave others untouched.
Term
Cell death is most profound for neurons, which are typically postmitotic and unable to be regenerated. ____ cells are capable of regeneration.
Definition
Glial
Term
Two very common mechanisms by which cells in the nervous stem die are 
Definition
excitotoxicity and oxidative stress
Term
What is gliosis?
Definition
In fact, neuronal cell death is generally accompanied by gliosis, in which there is hypertrophy and/or multiplication of glial cells. 
Term
Explain the excitoxicity of glutamate.
Definition
  • Glutamate elicits toxicity when it binds to NMDA receptors on neurons. These receptors allow the influx of Ca++, which with sufficient time and concentration induces apoptotic pathways in sensitive neurons.


  • Glutamate opens AMPA channels that pass way too much Na+. The influx of Na+ results in increased osmotic pressure, influx of water, cell swelling and bursting. This type of cell death is rapid and will also induce neuroinflammation- activation of reactive astrocytes and microglia.
Term
Explain the oxidative stress on brain
Definition
Caused by Reactive oxygen species from the oxidative phosphorylation used for ATP production
Term
Lipinski's rule of 5 for oral drugs (only!)
Definition
Ømolecular weight < 500
ØlogP < 5
Ø < 5 H-bond donors (sum of NH and OH)
Ø < 10 H-bond acceptors (sum of N and O)

 

Ø< 10 rotatable bonds
Term

Partition coefficient P (usually expressed as log10P orlogP) is defined as:

Definition
P  = x(octanol)/ x(aqueous)
Term

P is a measure of the relative affinity of a molecule for the lipid and aqueous phases in the _____.

Definition
absence of ionisation
Term
ØP is a measure of lipophilicity of the ___compound.
Definition
neutral 
Term

High P value =  

 

Low p value =  

Definition

High P value = lipophilic


 

Low p value = water soluble

Term
increase lipophilicity
Definition
ØMethyl
ØEthyl
ØChlorine
ØBromine
ØCH2Cl
ØC2H4Br
ØPhenyl rings

 

ØCarbocyclic rings
ØHigher order hydrocarbon chains
ØTrifluoromethane
Term
Structural features to reduce lipophilicity
Definition
ØPolar functional groups (containing electronegative atoms such as O, N, S).

ØGroups that ionize (form stabile anions and cations) at physiological pH:
ØOH
ØNH2
ØCOOH
ØOMe
ØN(CH3)2

 

ØCONH2
Term
‘Floppy’ compounds (those with more than
10 rotatable bonds) generally have_____
Definition
 poor oral bioavailability
Term
ØFairly rigid compounds (those with seven or
fewer rotatable bonds) generally exhibit
good-to-excellent ____,
independent of molecular weight. 
Definition
oral bioavailability
Term
T/F: 75% of CNS drugs are basic.
Definition
True
Term
3 benefits of increasing conformational rigidity
Definition

1. Increases potency

2. Increase BBB penetration 

3. increase oral absorption

Term
4 factors that reduce BBB penetration.
Definition
Ø– Increasing numbers of  polar functional groups, HBAs, HBDs, Mw, PSA.
ØAcidic functional groups – weak acids (CO2H) tend to be more permeable at lower pH. Acidic molecules in systemic circulation are mostly ionized and poorly lipophilic.
Make a P-gp efflux transporter substrate – the antihistamine Loratadine

 

ØCombine a P-gp substrate with a BCRP substrate – the anticancer drug Methotrexate
Term
Structure Modifications to Increase BBB Penetration
Definition
ØReduce Pgp efflux
ØReduce hydrogen bond donors
ØIncrease lipophilicity
ØReduce Molecular Weight
ØReplace carboxylic acid groups
ØAdd conformational rigidity

 

ØTry to hitch a ride on uptake transporters
Term

Dopamine is produced from ____.

Definition
Tyrosine
Term

Remember that dopamine cannot pass the BBB but ____ can.

Definition
L-Dopa
Term

T/F: Selective inhibition of one isoform of MAO

 

 increases dopamine levels 

Definition
False: Nonselective inhibition of MAO A/B does increase dopamine levels
Term
MAOs catalyze the ____of monoamine neurotransmitters
Definition
oxidative deamination 
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