Quiz 4 Flashcards
1
Q
Hormones
A
Chemicals produced by endocrine glands that travel to target cells via bloodstream
2
Q
Pituitary Gland (“Master Gland”)
A
- Controls other glands (adrenal, thyroid, gonads, mammary) and has systemic affects through release of hormones:
- Reproductive hormones:
- *Affect mood, cognition, behavior in both sexes
3
Q
Hormones and Emotions
A
- Testosterone increases libido in males, females.
- Oxytocin- Promotes bonding; released during labor (uterine contractions), during breast feeding (milk letdown), during coitus in females, males
- Prolactin released during breast feeding (milk production)
4
Q
Estrogen and Emotions
A
- Estrogen levels shift significantly during female’s life.
- Depression mirrors these changes in estrogen.
- Estrogen (estradiol) has profound effects on body & brain.
- It activates genes to synthesize gene products, including trophic factors & enzymes that synthesize & metabolize neurotransmitters & receptors in females.
- Affects the 3 main neurotransmitters involved in depression: Serotonin, Norepinephrine and Dopamine
- Dysregulation during estrogen fluctuations may cause somatic and brain abnormalities.
5
Q
Estrogen levels & Depression over the lifespan
A
Estrogen levels shift significantly during female’s life.
• Rise and cycle from puberty until menopause
• Rise dramatically during pregnancy
• Plummet postpartum
• Erratic during perimenopause (37-55)
• Minimal during menopause
• Depression mirrors these changes in estrogen.
Depression increases significantly during puberty.
• May worsen during luteal phase (14 days before) of cycle
• Major risk during postpartum after abrupt fall in estrogen
• Risk for depression, psychosis, mania
• Risk during perimenopause
6
Q
Estrogen: effects on body & brain
A
- It activates genes to synthesize gene products, including trophic factors & enzymes that synthesize & metabolize neurotransmitters & receptors in females.
- Affects the 3 main neurotransmitters involved in depression: Seratonin, Norepinephrine, and Dopamine
7
Q
Dysregulation during estrogen fluctuations may cause somatic and brain abnormalities.
A
- During perimenopause:
- Vasomotor sx’s (hot flashes, sweating) caused by dysregulation of hypothalamic thermoregulatory centers modulated by 5-HT, NE
- Sxs of depression
8
Q
Hormones and Cognitive Function
A
- Studies comparing premenopausal and postmenopausal women, women in various stages of pregnancy, and females and males with varying levels of hormones indicate that hormones affect cognitive function.
- Ultimately, cognition is determined by complex interaction of hormones and experience.
9
Q
Stressor
A
Event that has an arousing effect
10
Q
Stress responses
A
Behavioral and physiological responses to cope with stressor
•Exciting, sad, or frightening events elicit essentially same acute stress responses.
11
Q
Chronicity (of stress hormones)
A
Major problem today in humans
-we experience such high and long-lasting stress reactions (i.e. work, school).
12
Q
Stress Hormones: 2 biochemical pathways
A
“Fast response” by norepinephrine/epinephrine
•Prepares body for sudden burst of activity
“Slow response” by cortisol
•Prepares body for longer-lasting adaptations
•Activated in minutes to hours
•Helps body resist stressors
•Prepares body for longer-lasting adaptations (e.g., restoring energy that has been expended and making more available)
•Essential to life – without it you die; it’s how we deal with stress
13
Q
High cortisol causes =
A
•Increased appetite
•Weight gain
•Increased abdominal fat
•Increased risk of cardiovascular disease and insulin-resistant diabetes
•Glucose intolerance
•Increased risk of insulin-resistant diabetes (NIDDM)
•Damaged arteries leading to atherosclerosis
•Hypertension/water retention
•Muscle weakness
•*Causes depression
•Cortisol level that does not decrease in
diurnal (through urine) fashion throughout day may be a marker for major depression.
14
Q
*Cortisol and memory
A
- Chronic stress results in continued high level of cortisol, which destroys hippocampal cells.
- Impairs ability to provide negative feedback (which is when the brain is told to stop producing cortisol).
- Keeps levels high, etc. in a pathological, vicious circle.
- May impair memory
- PTSD (e.g., early sexual abuse) may decrease glucocorticoid-receptor density in hippocampus.
- Impairs ability of hippocampus to control cortisol
15
Q
Sleep Deprivation Consequences
A
•Even one night of < 7-8 hrs shows impairments in: mental acuity, memory (40% poorer after one night under 7-8 hrs) ,learning, reasoning, reaction time, executive functioning
Note:
•Effects are accumulative.
•Many times people are not aware of deficits and think they have “adapted.”
16
Q
Primary insomnia
A
- Difficulty initiating or maintaining sleep or having non-restorative sleep for at least one month
- Causes clinically significant distress or impairment in functioning
- No clear underlying cause and not due to another sleep disorder, psychiatric disorder, medical condition, medications, or other substances
Note:
- Insomnia can be transient, acute, or chronic
- **The most common sleep disorder; over 30% of primary care patients
17
Q
Secondary insomnia
A
•Underlying medical or psychiatric condition causing or significantly contributing to insomnia (e.g., psychiatric disorder, pain, medications, obstructive sleep apnea)
18
Q
Rule Out Causes of Insomnia
A
- Psychiatric conditions: MDD, Bipolar, Anx
* Medical conditions: chronic pain, hypertension, hyperthyroidism, diabetes, etc.
19
Q
*Hypothalamus & Sleep
A
The hypothalamus has a “sleep-wake switch.”
• Throughout day, various chemicals gradually increase, making a person feel increasingly tired.
• At bedtime, these combine w/ the “sleep” component of the “sleep-wake switch,” which releases GABA. – “puts the cortex to sleep”; Brain is inhibited and put to sleep.
• In AM, the “wake” component of the “sleep-wake switch” releases histamine, which “wakes up” the brain.
20
Q
Various factors interfere with slow-wave sleep:
A
- Apnea
- Periodic leg movement disorder
- Chronic pain
- *Corticotropic-releasing hormone (CRH), cortisol (stress) prevent slow-wave sleep.
- *Lack of exercise
21
Q
Drugs that interfere with NREM sleep:
A
• Most sedatives/hypnotics:
• All benzodiazepines (BZDs), including ones used for sleep
• Alcohol
• Many antihistamines
• Caffeine
• EXCEPTIONS
-The “Z” drugs: Ambien, Sonata, Lunesta
-Rozerem
-Melatonin Supplement
22
Q
Cognitive-Behavioral Therapy for Insomnia
A
- *Efficacy research has shown that cognitive and behavioral treatments, collectively called cognitive-behavioral therapy (CBT) are more efficacious than hypnotics - both in the short and long term.
- Although well accepted by pts, these techniques remain generally unknown and under-utilized by health-care practitioners.
23
Q
CBT for insomnia targets one or more of the following:
A
- Cognitive and psychological factors - Beliefs, expectations, appraisal, worry
- Behaviorally based factors that perpetuate insomnia - Maladaptive sleep habits, irregular sleep schedule
- Arousal reduction - Relaxation, meditation, biofeedback
- Didactic sleep hygiene education - Targeting factors interfering and promoting sleep
- Sleep restriction
- Stimulus-control therapy - Reduce anxiety or conditioned arousal pts may feel when attempting to go to bed and give a set of instructions designed to re-associate bed/bedroom w/ sleep
24
Q
The most efficacious/effective treatment for primary insomnia is:
A) Hypnotic drugs
B) Treating the underlying medical condition
C) CBT
D) These are all equally efficacious/effective.
A
C) CBT
25
The most common sleep disorder is chronic primary insomnia. (True or False)
True
26
1. Neuroplasticity:
A) Occurs primarily during the first few years of life but very little after that
B) Is involved in learning and memory
C) Is a key phenomenon in the rehabilitation of patients suffering from TBI
D) Both B and C
D) Both B and C
27
```
2. Which form of memory is most improved by “top-down” organizing of information?
A) Implicit memory
B) Procedural memory
C) Prospective
D) Declarative memory
```
D) Declarative memory
28
Neuroplasticity
The ability of the brain to change physically and chemically in response to neurodevelopment, behavior, environment
•Involved in learning, memory, adapting to lesions
•Occurs throughout lifetime, primarily stimulated by experience
29
Neurodevelopment starts on day __ of gestation
18
30
Neurogenesis
* Growth of new neurons
| * Mostly complete by end of 2nd trimester
31
Neuronal selection
* Selection of best neurons
| * Mostly complete by end of 2nd trimester
32
Migration
* Move to destinations
| * Starts by 8 wks and mostly complete by birth
33
Most myelination of prefrontal cortex is not complete until _______________.
- early adulthood
34
Competitive elimination
Reorganization, restructuring, pruning:
| •Intense during late childhood & adolescence
35
What age do the following processes stop? Neurogenesis, differentiation (specialization), myelination (formation of myelin), synaptogensis (formation of synapses), arborization (extension of dendrites), and competitive elimination.
•Continue throughout lifetime to some degree
Note:
- mostly occurs before birth
- most myelination of prefrontal cortex is not complete until early adulthood
36
Habituation
– Decreased response to stimulus
Specifically:
-influx of calcium ions in response to action potential decreases --> less NT's released at postsynaptic membrane & less depolarization of postsynaptic membrane
37
Sensitization
– Enhanced response
-Serotonin reduces K+ effluc through potassium channels, prolonging action potential on neuron --> more Ca2+ influx and increased transmitter release
38
*Long-term potentiation (LTP)
A change in amplitude of EPSP, which lasts from hours to days or longer, in response to stimulation of a synapse
•Occurs especially in hippocampus
•In hippocampus, LTP may be particularly likely due to high number of NMDA receptors on a type of pyramidal neuron in area CA1
•If at the same time, a stimulus B causes presynaptic neuron to release glutamate into the dendrites of this same postsynaptic neuron, the NMDA receptors can be activated, which leads to LTP.
•Thus, A and B can become associated in this neuron.
•Helps explain why “neurons that fire together wire together.”
39
AMPA-Glu receptor:
* When Glu binds, channel opens, allowing Na+ to enter and K+ to exit, causing an EPSP.
* Is the main receptor mediating fast excitation in CNS
MAIN DIFFERENCE FROM NMDA?
40
NMDA-Glu receptor
* A “coincidence detector” in that it opens its channel for Ca2+ influx if 3 events occur:
* Membrane has depolarized sufficiently to remove Mg2+ from blocking the pore.
* Glutamate has bound to NMDA receptor.
* Glycine (or serine) has bound to NMDA receptor (at a different site than Glu).
MAIN DIFFERENCE FROM AMPA?
41
Associative learning
– A form of learning in which unrelated stimuli become associated to produce a behavioral response. Ex: Classical conditioning
Note:
-different stimuli may cause different events required for "coincidence detector" (NMDA) to fire --> causing neuron to learn association.
42
SYNAPTIC CHANGES
• If procedures that produce habituation, sensitization, LTP, or associative learning are repeated a number of times, the behavioral changes can last much longer (days, months, life-time).
• Increased dendritic connections increase the number of synapses, thereby allowing more complex communication among a network of neurons
-Dendritic Spines: extensions of membrane that allows many more synapses
43
Dendritic Branching
• Complexity of dendritic branching (arborization) is associated with complexity of task being performed and changes by experience.
MORE COMPLEX TASK = HIGHER COMPLEXITY OF DENDRITIC BRANCHING
44
Neurotrophic factors:
* Stimulate growth of neurons, aid in repair
* Experience stimulates production.
Examples:
- Nerve growth factor (NGF)
- Brain derived neurotrophic factor (BDNF)
- Glial-derived neurotrophic factor (GDNF)
- Epidermal growth factor (EGF)
45
Neurogenesis
– Creation of new neurons
• Occurs when animals learn, especially in hippocampus
• Occurs in enriched environments
• New neurons found in complex-housed (with stimulation), compared to cage-housed animals
• Enhances latter learning (led to Head Start)
46
Explicit memory
Ability to store and retrieve a memory and know that one has retrieved the correct one:
- Declarative memory
- Conscious memory
- “Knowing that”
- Are specific modules specializing in specific explicit memories
- critically dependent on working memory
Examples:
- Semantic memory – Facts, general knowledge
- Episodic memory – Autobiographic
- Incidental memory
- Verbal/Nonverbal memory
- Words vs. pictures
- recent memory and remote memory
- Memorizing information from this course
47
3 processes/stages of Explicit memory
* Encoding
* Consolidation/storage
* Retrieval
48
Encoding
- Short-term storage, initial processing, working memory (short-term memory)
- limited capacity and decays quickly
49
Four components of working memory:
* “Phonological loop” for auditory
* “Visuospatial sketchpad” for visuospatial
* “Central executive”
* “Episodic buffer” for interaction of semantic memory on working memory (for gist)
50
Consolidation/storage
• Expression of genes, protein synthesis (for long-term memory), alteration & strengthening of synapses
51
Retrieval
- recalling information from long-term memory
52
Explicit memory & Hippocampal formation
* Involved in forming, maintaining, & retrieving new and fairly recent memories
* Left for verbal
* Right for nonverbal (e.g., faces, spatial information, melodies)
53
Explicit memory & Frontal lobes:
* Memory for temporal order of events (“recency memory,” “temporal memory”)
* Episodic memory of place & time of autobiographical information
* Executive component of working memory (ability to manipulate information being held briefly)
54
Memory storage
* Memories are stored in specific association cortices although storing requires above structures.
* Semantic knowledge is distributed throughout neocortex.
55
Memory deficits in explicit memory (but with implicit memory intact):
* Anterograde amnesia, confabulation, especially w/ lesions in hippocampal formation
* Anoxia/hypoxia – Oxygen deprivation
* Alzheimer’s disease (initial dysfunction of hippocampus, followed by more extensive cortical damage)
* Amnesia may be time-limited (ECT, head injury, transient global amnesia)
* Anterograde amnesia – Impaired ability to learn new information after a lesion
* Retrograde amnesia – Impaired ability to recall memories prior to lesion
* Minutes to years
* A temporal gradient often exists (e.g., Alzheimer’s).
* Recent lost before remote
56
Implicit memory
Individual can demonstrate knowledge (memory) but cannot explicitly retrieve the information:
• “Knowing how”
• “Procedural memory”
• Encoded in similar way as it was perceived
• Passive role during encoding (although repetition over many trials is usually required)
* Examples:
* Classical conditioning (Pavlovian) - Neutral stimulus becomes paired with response
* Operant conditioning (instrumental) – Consequences of a response increase or decrease probability of that response
57
Principles of neuroplasticity:
* “Behavioral change reflects brain change.”*
* “All nervous systems are plastic in the same general way.”*
* “Plastic changes are age-specific.”*
58
```
1. Neurotransmitters may:
A) Inhibit neurons
B) Excite neurons
C) Alter DNA function
D) All of the above
```
D) All of the above
59
1. Relative to excitation or inhibition, a neurotransmitter’s effect on the DNA of the postsynaptic neuron is delayed and lasts longer. (True of False)
A) True
60
Neurons
• Basic signaling units, information processors, computational devices, CPU’s
61
Glia (glial cells)
• the support cells (structural and functional support)
62
Resting Membrane Potential
* At rest, neuron has electrical potential (charge across its membrane) of -70 mV (inside negative relative to outside) due to unequal distribution of charged particles (ions, proteins)
* It is said to be “polarized.”
63
Resting potential created by:
* Semipermeability of membrane
| * Hard for Na+ to pass into neuron, and proteins (mostly negative charge) are kept inside due to size & charge
64
Synapse
– Site of functional contact
65
Graded Potentials
If Na+ or Ca++ channels open, Na+ or Ca++ can enter.
• Charge on membrane becomes less negative, or depolarized (excited).
• It is now closer to its firing threshold of -50 mV.
• Is an excitatory post-synaptic potential (EPSP)
If Cl- or K+ channels open, Cl- or K+ can exit.
• Charge on membrane becomes more negative, or hyperpolarized (inhibited).
• It is now further from its firing threshold of -50 mV.
• Is an inhibitory post-synaptic potential (IPSP)
66
Firing is termed
- an “action potential”
| • The amplitude is constant for all action potentials (“all-or-none”)
67
Saltatory conduction
Action potential “jumps” from node to node
• Is possible because of myelin (prevents ions from crossing membrane - so no action potential)
• Through myelinated portions, current is passively transmitted extremely fast.
• At nodes of Ranvier, there is no myelin but rich in voltage-sensitive channels
• Where action potential is re-generated
• Greatly increases speed
68
Action potentials
* Amplitude of action potential is constant and cannot provide information about intensity.
* Intensity is provided by frequency of action potentials because more intense stimulus increases probability that firing thresholds will be reached and that action potentials will be generated.
* Duration of stimulus is reflected in period over which action potentials occur (total number).
* Brain processes patterns of these action potentials.
69
Multiple sclerosis (MS)
* Episodic, inflammatory, multifocal disease
* Likely is an autoimmune response against myelin antigens in CNS
* Less myelin slows speed of propagation and causes “cross-talk” (“short-circuiting”) in motor, sensory axons.
* Affects optic nerves, cerebral hemispheres, brainstem, cerebellum, spinal cord
* Most types have mood & affective instability, alterations in behavior or personality, which usually occur throughout illness.
* Mild-moderate cognitive deficits (e.g., attention, speed of information processing, memory recall, executive functioning) in > 50%
* Severe cognitive decline in 20-30%
70
Two most common types of MS
1. Relapsing-remitting (RRMS)
• Accounts for 80-85% of new cases of MS
• After 15 yrs, most evolve into secondary progressive MS (SPMS)
• Most will require assistance w/ ambulation; some will become totally dependent for ADL’s
2. Primary progressive MS – 15-20% of new cases
71
Glutamate (Glu)
* generally excites neurons.
| * Most common excitatory NT
72
Gamma-aminobutyric acid (GABA)
* generally inhibits neurons.
| * Most common inhibitory NT
73
Acetylcholine (ACh)
* the NT used for neuromuscular transmission.
| * When ACh is released at neuromuscular junction, it leads to muscular contraction.
74
Histamine (H)
* From the tuberomammillary nucleus (of the hypothalamus) is the NT in the “wake” nucleus of the “sleep-wake switch” of the hypothalamus.
* When released, it wakes up the cortex and inhibits the “sleep” nucleus of the hypothalamus.
75
Dopemine (DA)
* DA cell bodies in substantia nigra project primarily to striatum of BG (nigrostriatal pathway)
* When 90% of DA neurons die here, get Parkinson’s disease
76
NE cell bodies in the locus coeruleus project to entire cortex:
* Activates cortex for alertness, responsiveness to novel stimuli, response to stressful stimuli (especially fear)
* At times, produces positive feelings of reward, helps maintain emotional tone, inhibits pain
77
Neurotransmitter synthesis & storage:
• Most neurotransmitters are synthesized in axon terminal and stored in synaptic vesicles until needed.
78
Steps of neurocommunication?
* Release of NT
* Activation occurs when neurotransmitter binds to specific binding site on specific receptor (protein in postsynaptic membrane). This causes:
* Excitation or
* Inhibition or
* Initiation of other chemical reactions
* Deactivation of neurotransmitter:
* Reuptake:
* Neurotransmitter or its degraded end-product taken up by presynaptic membrane via transporter proteins (“reuptake pumps”)
* Most common type of deactivation
* Enzymatic degradation (e.g., monoamine oxidase)
* Simple diffusion
* Taken up by glia, which may degrade or store neurotransmitter for re-export to axon terminal
79
Transmembrane Signaling
* Problem: For a neurotransmitter to affect a cell, its “signal” must pass that neuron’s lipid-bilayer membrane.
* Most molecules, including ions, cannot cross because they are charged or not sufficiently lipophillic.
Two families of receptors for circumventing barrier posed by the membrane.
• 1st family is comprised of ionotropic receptors (ligand-gated channels)
- Allow movement of ions across membrane through a gate that opens when neurotransmitter binds
- Rapid change in membrane potential (msec’s)
- Mediate fast behavior
- May be excitatory or inhibitory
• 2nd family is comprised of metabotropic receptors
- Alter internal chemistry, including altering ion channels and activating enzyme
- Enzyme can activate a “second messenger,” which in turn can activate other enzymes that can affect many chemical reactions (2nd messenger cascade)…
80
Metabotropic
* “2nd messenger” can travel to nucleus and affect DNA resulting in change in production of proteins (gene transcription)
* Formation of new receptors, enzymes, trophic factors
* Up-regulation – Increase in number or sensitivity of receptors
* Down-regulation – Decrease in number or sensitivity of receptors
81
Neurotransmitters that generally alter the internal chemistry of neurons:
* Acetylcholine (ACh) when binding to muscarinic receptors
* Dopamine (DA)
* Norepinephrine (NE)
* Epinephrine (E)
* Serotonin (5-HT)
* Glutamate (Glu) when binding to specific subtypes of receptors
82
Metabotropic Receptors
Modulate synaptic actions & behavior by altering excitability of neurons, strength of synapses and efficiency of neurocommunication.
• Such modulatory synaptic pathways can act as crucial reinforcing pathways during process of learning. (Neuroplasticity)
• Hormones bind to metabotropic receptors.
83
Characteristics of metabotropic receptors:
* Tremendous amplification of signal
* Flexibility & diversity of responses
* Can affect ion channels, membrane potentials, enzyme activity, gene transcription (protein production)
* Diversity of receptor subtypes
* When protein synthesis is involved:
* Onset of action will be delayed 30 minutes to hours.
* Effects will persist hours to days (or longer) after concentration of neurotransmitter has been reduced to zero due to slow turnover of proteins.
84
Cortisol
- Promotes protein breakdown (which can lead to muscle weakness/wasting)
- Shuts down systems that aren't immediately necessary
- immune system - which can lead to infections,
- reproductive system - which can lead to infertility, decreased libido, and amenorrhea
- inhibits inflammatory response
- inhibits slow wave sleep
85
CRH or CRF
Corticotrophin-Releasing Hormone or Corticotrophin Releasing Factor
- released by hypothalamus in response to stress
- increased ACTH - which increases cortisol
- May cause: depression/anxiety, brain dysfunction/damage
