Midterm review Flashcards
Identify the substrates that PKA/G enzymes act on to influence cellular response patterns
- Voltage-gated ion channels
- Ligand-gated ion channels
- Synaptic vesicle proteins
- Enzymes involved in neurotransmitter synthesis
- Proteins that regulate gene transcription
Describe the structure of the blood-brain barrier
The blood-brain barrier is the separation between brain capillaries and the brain/cerebrospinal fluid, and it is selectively permeable; it allows lipid soluble molecules
Give a step-by-step account of how the process of neurotransmission works.
- ) Neurotransmitter is synthesized and then stored in vesicles
- ) An action potential invades the presynaptic terminal
- ) Depolarization of presynaptic terminal causes opening of voltage-gated Ca2+ channels
- ) Influx of Ca2+ ions through channels
- ) Ca2+ causes vesicles to fuse with presynaptic membrane
- ) Neurotransmitter is released into synaptic cleft via exocytosis
- ) Neurotransmitter binds to receptor molecules in postsynaptic membrane
- ) Opening or closing of postsynaptic channels
- ) Postsynaptic current causes excitatory or inhibitory postsynaptic potential that changes the excitability of the postsynaptic cell
- ) Retrieval of vesicular membrane from plasma membrane
What is number 2 on figure 3.16?
An action potential invades the presynaptic terminal
What is number 3 on figure 3.16?
Depolarization of presynaptic terminal causes opening of voltage-gated Ca2+ channels
What is number 4 on figure 3.16?
Influx of Ca2+ ions through channels
What is number 5 on figure 3.16?
Ca2+ causes vesicles to fuse with presynaptic membrane
What is number 6 on figure 3.16?
Neurotransmitter is released into synaptic cleft via exocytosis
What is number 7 on figure 3.16?
Neurotransmitter binds to receptor molecules in postsynaptic membrane
What is number 8 on figure 3.16?
Opening or closing of postsynaptic channels
What is number 9 on figure 3.16?
Postsynaptic current causes excitatory or inhibitory postsynaptic potential that changes the excitability of the postsynaptic cell
What is number 10 on figure 3.16?
Retrieval of vesicular membrane from plasma membrane
What is number 10 on figure 3.16?
Retrieval of vesicular membrane from plasma membrane
For the 5 major divisions of the brain (-cephalons), identify a structure, substructure, and general function for that substructure.
- Myelencephalon (structure: medulla; substructure: area postrema); the area postrema initiates vomiting in response to toxins in the blood
- Metencephalon (structure: pons; substructure: reticular formation); the reticular formation is involved in arousal, attention, sleep, and muscle tone
- Mesencephalon (structure: tegmentum; substructure: periaqueductal gray); the periaqueductal grey is responsible for pain modulation
- Diencephalon (structure: thalamus; substructure: lateral geniculate nucleus); the lateral geniculate nucleus is responsible for receiving visual info from the eyes and projecting it to the primary visual cortex
- Telencephalon (structure: limbic system; substructure: amygdala); the amygdala is involved in emotional responses
What are the 5 major divisions of the brain?
- Myelencephalon
- Metencephalon
- Mesencephalon
- Diencephalon
- Telencephalon
What is a structure of the myelencephalon?
Medulla
What is a substructure of the medulla?
Area postrema
What is a function of the area postrema?
Initiating vomiting as a response to toxins in the blood
The area postrema is located in what division of the brain?
Myelencephalon
What is a structure of the metencephalon?
Pons
What is a substructure of the pons?
Reticular formation
What is a function of the reticular formation?
Sleep, arousal, attention, muscle tone
The reticular formation is located in what division of the brain?
Metencephalon
What is a structure of the mesencephalon?
Tegmentum
What is a substructure of the tegmentum?
Periaqueductal grey
What is a function of the periaqueductal grey?
Pain modulation
The periaqueductal grey is located in what division of the brain?
Mesencephalon
What is a structure of the diencephalon?
Thalamus
What is a substructure of the thalamus?
Lateral geniculate nucleus
What is a function of the lateral geniculate nucleus?
Receiving visual info from the eyes and projecting it to the primary visual cortex
The lateral geniculate nucleus is located in what division of the brain?
Diencephalon
What is a structure of the telencephalon?
Limbic system
What is a substructure of the limbic system?
Amygdala
What is a function of the amygdala?
Emotion
The amygdala is located in what division of the brain?
Telencephalon
The amygdala is located in what division of the brain?
Telencephalon
Explain what the resting membrane potential is and how it is generated.
- The resting membrane potential is the difference in electrical charge inside the cell compared with outside the cell
- Equal to -70mV
- It is generated because of selective permeability of the membrane and uneven distribution of ions inside and outside the cell
What is the resting membrane potential?
The resting membrane potential is the difference in electrical charge inside the cell compared with outside the cell
How is the resting membrane potential generated?
It is generated because of selective permeability of the membrane and uneven distribution of ions inside and outside the cell
Explain what reliability and validity are in scientific research
- Validity is the extent to which the research is consistent with human subjects
- Reliability refers to the extent to which the tests can be replicated and have the same result
What is reliability?
The same results will be recorded each time the test is used
What is validity?
The expectation that the variable that is being measured reflects the variable that is meant to be measured
What is long-term potentiation and how does it work?
- Long-term potentiation is a persistent increase in synaptic strength produced by a burst of activity in the presynaptic neuron
- The burst of firing is produced experimentally by a single brief train of electrical stimuli
- Two types: early and late
- Late LTP requires early LTP to be initiated first
- Early LTP lasts a few hours at most
- LTP occurs throughout the brain but is most studied in hippocampal pyramidal cells
What is long-term potentiation?
A persistent increase in synaptic strength produced by a burst of activity in the presynaptic neuron
How does long-term potentiation work?
A burst of firing is produced experimentally by a single brief train of electrical stimuli which strengthens the synaptic strength
Outline the roles of glutamate and GABA in epileptic seizures
- Associations between mutations in the GABA(A) receptor subunits and various types of seizure disorders confirm that normal GABA(A) receptor functioning is required to prevent abnormal increases in brain excitability
- The cause of some epileptic seizures involves a defective GABAergic process of hyperpolarization of neurons after prolonged depolarization
- In cases without GABA(A) receptor mutations, dysregulation of the GABAergic systems may still be involved
Mutations in what type of receptor subunits are linked to various types of seizure disorders?
GABA(A)
Normal GABA(A) receptor functioning is require to prevent what?
Abnormal increases in brain excitability
In cases of seizure disorders without GABA(A) receptor mutations, what else could be involved?
Dysregulation of the GABAergic systems
Explain the rat park experiments and their importance in our understanding of drug addiction and research
- An experiment that involved separating rats into isolated or socialized groups
- They were given an initial choice of morphine laced water, and then only morphine water, and then alternating
- No gender differences, but some difference between groups (isolated rats chose morphine water more often)
- This is important because many human addicts experienced neglect, isolation, etc. prior to drug abuse
What was the order of choices given to subjects in the rat park experiments?
They were given an initial choice of morphine laced water, and then only morphine water, and then alternating
Was there any gender differences in the rat park experiments?
No significant differences
Was there between group differences in the rat park experiments?
Yes, isolated rats chose morphine water more often
Why are the rat park experiments important in our understanding of drug addiction and research?
This is important because many human addicts experienced neglect, isolation, etc. prior to drug abuse
Explain serotonin’s role in pain modulation, including the roles of specific 5-HT receptor subtypes
- Descending serotonergic fibres receive input from the periaqueductal grey and synapse to the dorsal horn neurons of the spinal cord
- Serotonin along this pathway tends to inhibit pain signals from periphery through 5HT(1b) and 5HT(3) receptors
Serotonin activity along the pathway between the periaqueductal grey and spinal cord tends to inhibit pain signals from periphery through what receptors?
5HT(1b) and 5HT(3)
Summarize norepinephrine’s role in arousal and cognition
- Prefrontal cortex expresses abundance of α1 and α2 receptors; α2 agonists produce an increase in working memory and α1 agonists decreases cognitive performance, indicating a homeostatic balance between these two receptors
- LC neurons fire more rapidly during waking than during sleep; projetions to medial septal nuclei and medial preoptic area (hypothalamus) initiate this arousal
The prefrontal cortex expresses an abundance of what receptors?
α1 and α2
What do α2 agonists do?
Produce an increase in working memory
What do α1 agonists do?
Decrease cognitive performance
All drug experiences are a function of dose, set, and setting. Give a brief historical account of drug prohibition and briefly speculate about how these events have influence the set and setting parameters today
- Prior to 1914, ALL drugs were legal, and then in 1914 they could only be prescribed
- Alcohol prohibition came in 1919 and was appealed in 1933 (this is in the US)
- 1937 marihuana tax act passed
- 1969 Leary vs US - supreme court case that overturned the marihuana tax act
- Modern war on drugs began in 1970
- This history helped develop a system for determining drug parameters based on abuse potential and risk potential (for example, some drugs like heroin have a high abuse potential and a high risk potential, with no medical use)
Prior to what year were all drugs legal?
1914
When was the alcohol prohibition introduced?
1919
When was the alcohol prohibition appealed?
1933
When did the modern war on drugs begin?
1970
Delineate the three dopamine pathways that originate in the midbrain and identify each of their primary functions
- The nigrostriatal pathway originates in the substantial nivea and innervates the caudate-putamen
- The mesolimbic pathway originates in the VTA and innervates various limbic system structures
- The mesocortical pathway originates in the VTA and innervates the cerebral cortex
- The nigrostriatal pathway is linked to voluntary movement
- The mesolimbic and mesocortical pathways have been implicated in the neural mechanisms underlying drug abuse and schizophrenia
What are the three dopamine pathways that originate in the midbrain?
- Nigrostriatal
- Mesolimbic
- Mesocortical
Delineate the nigrostriatal pathway
The nigrostriatal pathway originates in the substantial nivea and innervates the caudate-putamen
Delineate the mesolimbic pathway
The mesolimbic pathway originates in the VTA and innervates various limbic system structures
Delineate the mesocortical pathway
The mesocortical pathway originates in the VTA and innervates the cerebral cortex
How is ethanol metabolized in humans? Outline some of the ethnic and sex differences in this process.
- Once consumed, it is diffused passively into the blood
- 10% absorbed in the stomach, 90% absorbed in the small intestine
- Once in circulation it moves to all tissue, not just the brain
- Liver enzymes break it down at a constant rate
- Majority of it is broken down by enzymes cytochrome P450 and alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH)
- Alcohol has a proportionally greater effect on women (due to body size)
- Some enzymes are more active in men
- B1 deficiency is greater in alcoholic women
The majority of ethanol is broken down by what enzymes?
Cytochrome P450 and alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH)
Outline the neurochemical targets of ethanol. How does it affect various neurotransmitter receptor subtypes?
- Glutamate: has a high affinity for NMDA glutamate receptors; ethanol acts as an antagonist inhibits glutamate neurotransmission by reducing the effects of glutamate at NMDA receptor; induces memory loss, hyper excitability, excitotoxicity
- GABA: ethanol acts as an agonist and enhances GABA induced chloride entry and hyper polarization by modulating extra synaptic GABA(A) receptors and stimulating GABA release; chronic alcohol consumption causes down-regulation of GABA(A) receptors which increases the likelihood of seizures and lowers the effects of benzodiazepine
- Dopamine: ethanol increases firing rate of mesolimbic neurons; activates dopaminergic cells in VTA; positive reinforcement which leads to repeated drug use
Identify the five factors that influence drug action and give an example influence for each of them
- Routes of administration
- Absorption and distribution
- Binding
- Inactivation
- Excretion
Identify all of the ways in which drugs can affect synaptic transmission
- Drug serves as neurotransmitter precursor
- Drug inhibits neurotransmitter synthesis
- Drug prevents storage of neurotransmitter in vesicles
- Drug stimulates release of neurotransmitter
- Drug inhibits release of neurotransmitter
- Drug stimulates postsynaptic receptors
- Drug blocks postsynaptic receptors
- Drug stimulates autoreceptors; inhibits release of neurotransmitter
- Drug blocks autoreceptors; increases release of neurotransmitter
- Drug inhibits neurotransmitter degradation
- Drug blocks reuptake
List all of the receptor subtypes (both ionotropic and metabotropic) for acetylcholine
α, β, γ, δ, ε
Explain the structure and function of the glutamate NMDA receptor
- Ca2+ can act as a second messenger, which makes NMDA both ionotropic and metabotropic
- In order to stimulate the NMDA receptor and open its ion channel, both glutamate and glycine are required
- Mg2+ binding site blocks the channel even in presence of glutamate and co-agonist until membrane is depolarized
Describe the neurobiology of drug reinforcement
- Reward circuit: VTA mesolimbic dopaminergic neurons code for reward prediction error; Fibers terminate in NAcc, amygdala, and prefrontal cortex; Amygdala has reciprocal connections with NAcc and BNST; NAcc has subsequent output to the ventral pallidum VP
- Once a reward is paired with a conditioned stimulus, these neurons will fire in response to the conditioned stimulus even before the reward is signalled (reward prediction); Failure of reward after conditioned stimulus leads to decreased activity (prediction error)
What are the 3 types of validity?
- Face validity
- Construct validity
- Predictive validity
What are the five gross categories of drugs?
- CNS stimulants
- CNS depressants
- Analgesics
- Hallucinogens
- Psychotherapeutics
What is an example of a CNS stimulant?
- Amphetamine
- Cocaine
- Nicotine
What is an example of a CNS depressant?
- Barbiturates
- Alcohol
What is an example of an analgesic?
- Morphine
- Codeine
What is an example of a hallucinogen?
- Mescaline
- LSD
- Psilocybin
What is an example of a psychotherapeutic?
- Prozac
- Thorazine
Describe a psychological effect of a CNS stimulant at a typical dose
Increased electrical activity in the brain and behavioural arousal, alertness, and a sense of well-being in the individual
Describe a psychological effect of a CNS depressant at a typical dose
Depress CNS function and behaviour to cause a sense of relaxation and drowsiness
Describe a psychological effect of an analgesic at a typical dose
Reduce the perception of pain
Describe a psychological effect of a hallucinogen at a typical dose
Alter one’s perceptions, leading to vivid visual illusions of distortions of objects and body image
Describe a psychological effect of a psychotherapeutic at a typical dose
Treat clinical disorders of mood or behaviour
List the cranial nerves, what they involve, and whether they are sensory or motor
- Olfactory - smell (S)
- Optic - vision (S)
- Oculomotor - moves the eyes (M)
- Trochlear - moves the eyes (M)
- Trigeminal - face, sinuses, teeth, jaw muscles (S/M)
- Abducens - moves the eyes (M)
- Facial - tongue, soft palate, facial muscles, salivary glands, tear glands (S/M)
- Vestibulocochlear - inner ear, hearing and balance (S)
- Glossopharyngeal - throat muscles, taste, and mouth sensations (S/M)
- Vagus - info from internal organs (S/M)
- Spinal accessory - neck muscles (M)
- Hypoglossal - tongue muscles (M)
Is the Olfactory cranial nerve sensory or motor?
Sensory
Is the optic cranial nerve sensory or motor?
Sensory
Is the oculomotor cranial nerve sensory or motor?
Motor
Is the trochlear cranial nerve sensory or motor?
Motor
Is the trigeminal cranial nerve sensory or motor?
Both
Is the abducens cranial nerve sensory or motor?
Motor
Is the facial cranial nerve sensory or motor?
Both
Is the vestibulocochlear cranial nerve sensory or motor?
Sensory
Is the glossopharyngeal cranial nerve sensory or motor?
Both
Is the vagus cranial nerve sensory or motor?
Both
Is the spinal accessory cranial nerve sensory or motor?
Motor
Is the hypoglossal cranial nerve sensory or motor?
Motor
What does the optic cranial nerve involve?
Vision
What does the oculomotor cranial nerve involve?
Muscles that move the eyes
What does the trochlear cranial nerve involve?
Muscles that move the eyes
What does the abducens cranial nerve involve?
Muscles that move the eyes
What does the trigeminal cranial nerve involve?
Face, sinuses, teeth, jaw muscles
What does the facial cranial nerve involve?
Tongue, soft palate, facial muscles, salivary glands, tear glands
What does the vestibulocochlear cranial nerve involve?
Inner ear, hearing and balance
What does the glossopharyngeal cranial nerve involve?
Throat muscles, taste and other mouth sensations
What does the vagus cranial nerve involve?
Internal organs, info from internal organs
What does the spinal accessory cranial nerve involve?
Neck muscles
What does the hypoglossal cranial nerve involve?
Tongue muscles
Delineate the Gq second messenger signalling pathway.
- Gq-protein binds to PLC, PLD, PLA2
- PLA2 hydrolyzes PI, releasing arachidonic acid
- PLD hydrolyzes other membrane lipids, producing anandamide
- PLC hydrolyzes PIP2 into inositol IP3 and DAG
- DAG remains in membrane and activates PKC
- IP3 binds to Ca2+ channel receptors on endoplasmic reticulum
