Week 1-2 Flashcards
<p>What areneurons and synapses</p>
<p>Neurons</p>
<ul> <li>Cells in the nervous system</li> <li>Electrical signals (“action potentials”) are transmitted along the axons.</li></ul>
<p>Synapses</p>
<ul> <li>Where neurons meet</li> <li>Chemical signals (“neurotransmitters”) transmitted between neurons</li></ul>
<p>How do neurons in the CNS, PNS, ENS communicate?</p>
<p>What is the function?</p>
<ul></ul>
<ul> <li>All neurons in the CNS, PNS and ENS communicate through chemical signals (Neurotransmitters & neuromodulators). <ul> <li>Chemicals modulate neural activity and other functions like synaptic plasticity</li> <li>Without these chemical signals, the action of one neuron would not influence any other neuron in the nervous system (no brain integration and no useful brain function).</li> </ul> </li></ul>
<p></p>
<p>How many neurons are there in the CNS</p>
<p>100 billion neurons in the CNS</p>
<p>What are hormones</p>
<p>Signaling molecules produced by glands and transported through the blood to regulate physiology (muscles, neurons etc) and behaviour.</p>
<p>Also directly modulate NT levels and function (<em>sex hormones</em>)</p>
<p>4 differencses between NT and hormones</p>
<p><u>NT</u></p>
<ul> <li>Nervous system</li> <li>Tramission between neurons (Across synapse)</li> <li>Target cells can be specific neurons or other cells</li> <li>Generally fast (ms), though sustained NT release can lead to more sustained changes in brain</li></ul>
<p><u>Hormones</u></p>
<ul> <li>Endocrine system</li> <li>Travel by blood</li> <li>Target cells can be some distance from endocrine gland</li> <li>Much slower, ranging from few seconds to days</li> <li>Also directly modulate NT levels and function</li></ul>
<p>What is the blood-brain barrier? (Location, Function)</p>
<p><u>Location</u></p>
<ul> <li>Exists within 600km of blood vessels in the CNS</li></ul>
<p><u>Function</u></p>
<ul> <li>Prevents many substances from passing betweenblood andbrain.</li> <li>Many drugs, natural chemicals and foreign infections cant pass through (but is not perfect – small amounts of many things still get through).</li> <li>However, multiple other avenues for controlled passage between blood and nervous system exist.</li></ul>
<p>What is the PNS (Location, Function)</p>
<p><u>Location</u></p>
<ul> <li>Nerves and ganglia outside of the brain and spinal cord</li></ul>
<p><u>Function</u></p>
<ul> <li>Receives sensory information about body position, pain and temperature, etc</li> <li>Sends messages from the brain to control muscles and movement.</li></ul>
<p>What is the ENS (Locaton - 1, how many neurons - 1 , properties - 6, function - 3)</p>
<p><u>Location</u></p>
<ul> <li>ENS (2nd brain) is <u>part of</u> the PNS</li></ul>
<p><u>How many neurons</u></p>
<ul> <li>Contains 100million neurons</li></ul>
<ul></ul>
<p><u>Properties</u></p>
<ul> <li>Has its own reflexes and senses and can act independently of the brain</li> <li>Does not engage in consciousness, philosophy, decision-makingdespite being so much like our “main” brain.</li> <li>Only part of the PNS that can act autonomously</li> <li>Nearly every neurotransmitter found in the brain is also found in the gut</li> <li>95% of all our serotonin is found in the gut</li> <li>90% of connections between the brain and gut go from the gut to the brain.</li></ul>
<p><u>Function</u></p>
<ul> <li>Helps digestion</li> <li>Plays a major role in emotions, stress (butterflies in our stomachs)</li> <li>Links between gut health and clinical depression / anxiety.</li></ul>
<p>What are the 3 systems in the gut-brain interaction (And elaborate)</p>
<p>1. Peripheral Serotonin</p>
<ul> <li>Cells in gut produce serotonin, affecting brain given the large amount of connectivity from gut to brain</li></ul>
<p>2. Immune System</p>
<ul> <li>Intestinal microbiome can promptimmune cells to produce cytokines, affecting neurophysiology</li></ul>
<p>3. Bacterial Molecules</p>
<ul> <li>Microbes produce metabolites (e.g. butyrate), affecting activity of cells in blood-brain barrier</li></ul>
<p>What is microbiome and microbiota</p>
<p><u>Microbiome</u></p>
<ul> <li>Combined genetic material of microbiota</li> <li>> 100 times more genes than the human genome</li></ul>
<p><u>Microbiota</u></p>
<ul> <li>Trillions of bacteria and other microorganisms that live in the gut</li> <li>Impacts brain, behaviour, cognition <ul> <li>Shy mice became "adventurous" after receiving gut microbiota transplant from social mice</li> </ul> </li></ul>
<p>How does the gut microbiota influence the brain</p>
<p>How does the brain influence the gut (neurophysiologically)</p>
<ul> <li>Gut microbiota impacts brain via modulating<strong>immune, circulatory and neural </strong>pathways, ensuring homeostasis and development</li> <li>CNS impacts the gut via <strong>neural and endocrine</strong> response</li></ul>
<p>What is Gut Microbiota Dysbiosis and What are the risk factors?</p>
<p>Gut Microbiota Dysbiosis:</p>
<ul> <li>Imbalance of gut microbiota, leading to potential for disease</li></ul>
<p>Risks:</p>
<ul> <li>Genetic</li> <li>Low Sunslight/Vitamin D</li> <li>Tobacco Smoke</li> <li>Obesity</li> <li>Shift-Work (Sleep)</li> <li>Epstein-Barr Virus <ul> <li>Not everyone develops diseases from these risk factors</li> </ul> </li></ul>
<p>What is the link between sickness behaviour and brain</p>
<p>Bidirectional link between brain to immune system and immune system to brain</p>
<p>Activation of the immune system due to illness triggers a series of temporary behavioural, cognitive and emotional changes including:</p>
<ul> <li>Fever</li> <li>Increased sleep & general lethargy</li> <li>Depressed mood</li> <li>Hyperalgesia (increased pain sensations)</li> <li>Loss of interest in usual activities</li> <li>Anorexia (reduced appetite)</li> <li>Decreased social interaction</li> <li>Impaired concentration</li></ul>
<p>How does cytokines affect the brain?</p>
<p>Too big to pass through BBB.</p>
<p>Enter brain indirectly or trigger new cytokines to be released in the brain</p>
<p>What is an example of our integrated brains</p>
<p>Kissing</p>
<ul> <li>Increases risk of transmitting illness</li> <li>Allows transfer of hormones like testosterone to passed on to directly increase arousal</li> <li>Others suggest it is a show of trust and close bond (either between the individuals or to the public)</li></ul>
<p></p>
<p>What is sickness behaviour thought to be</p>
<p>Strategy to conserve energy and improve fight against infection</p>
<p>Define "Stress"?</p>
<p>What feelings is it associated with?<br></br></p>
<ul> <li>Stress is a response to a <u>perceived</u> aversive or threatening situation</li> <li>Feelings of being overloaded, wound-up tight, tense and worried.</li></ul>
<p>Is stress positive or negative?</p>
<p>Both</p>
<p><u>Positive</u>:</p>
<ul> <li>Exciting, motivating, improving alertness & performance</li></ul>
<p><u>Negative</u>:</p>
<ul> <li>Harmful for health and function</li></ul>
<p>What is a critical component of a stress experience?</p>
<p>What are thrill seekers attracted to?</p>
<p>Critical Component</p>
<ul> <li><u>Real</u> or <u>perceived</u> lack of control over the stressor (Threat of bad events without control is sufficient)</li> <li><strong>Thrill seekers</strong> are often attracted to “calculate risks,”<strong> with some<em>but not total</em> </strong>control of the risk (Complete lack of control is generally negative)</li></ul>
<p>What are the 3 types of stress. What are the differences.</p>
<p><u>1.) Acute Stress</u></p>
<ul> <li>Single eventthat leads to increased “flight or fight” response, raising arousals</li></ul>
<p><u>2.) Episodic Acute Stress</u></p>
<ul> <li>Repeated (but <strong>independent</strong>) acute stress events <ul> <li>e.g. life chaos, excessive worry about normal events.</li> </ul> </li></ul>
<p><u>3.) Chronic Stress</u></p>
<ul> <li>Seemingless endless and uncontrollable</li></ul>
<p>What is the advantage of animal models of stress</p>
<p>Human studies are correlational or observational (ethics)</p>
<p>Animal studies provide direct measures of effects of different types of stress on biology</p>
<p>What is the key brain region in stress?</p>
<p>Whatare the 2brain systems mediating stress?</p>
<p>Explan the process briefly.</p>
<p><u>Acute stress response:Fight or Flight</u></p>
<ul> <li>Rapid detection of threat in the amygdala</li> <li>Activates hypothalamus (<u><strong>Key coordination centre</strong></u>)</li> <li>Activate the HPA axis and sympathetico-adrenal-medullary pathway <ul> <li>HPA system (Hypothalamus > Putiliary Gland > Adrenal Gland) <ul> <li><strong>Cortisol</strong></li> </ul> </li> <li>Sympathetic Nervous System <ul> <li><strong>Epinephrine/Norepinephrine</strong></li> </ul> </li> </ul> </li></ul>
<p>Coritsol & NA facilitates the fight or flight</p>
<p>Explain the HPA Axis Process</p>
<ol> <li><strong>H</strong>ypothalamus activated (Triggers emotional responses)</li> <li><strong>P</strong>ituitary Gland activated</li> <li><strong>A</strong>drenal Cortex activated (Adrenal Gland)</li> <li>Releases cortisol (detected in blood)and adrenaline</li> <li>Increases metabolism, blood flow, HR</li></ol>
<p></p>
<p>Explain the different process in acute moderate vs high stress</p>
<p><u>Moderate</u></p>
<ul> <li>Aroused & optimal functioning ofPFC</li> <li>Allow top-down regulation of thought, actions & emotions</li></ul>
<p><u>High</u></p>
<ul> <li>Impaired optimal PFC function</li> <li>Since PFC has inhibitory inputs into subcortical arousal structures (e.g., basil ganglia, amygdala), this increases the influence of emotional responses, habitual action and bodies arousal response</li></ul>
<p></p>
What are the 3 effects of acute stress on the brain
PFC Impaired
- Weakened Inhibitory Control (Substance Abuse)
Amygdala Strengthened
- Increased memory consolidation of stressful events
- Increased fear conditioning
What are the 3 effects of chronic stress on the brain (Brain parts)
Hippocampus:
- Episodic Memory
- Declarative Memory
PFC:
- Working Memory
- Fear Extinction
Amygdala:
- Aggression
- Emotional Memory
Why does stress increase sensitivity to stress?
Hippocampus: Contextual Learning
- Impaired emotional and memory function reduces flexible emotional processing and reduce separation between memories
- Causes overgeneralization and less capacity cope with new real or potential stressful events.
What are the effects of a.) acute (1) and b.) chronic stress (3) on the body?
Release of glucocorticoids (e.g. cortisol) triggers
Acute effects
- Increased energy availability in muscles and breaking down fats & proteins to glucose.
Chronic effects
- Suppress immune system
- i.e, train drivers that injure or kill people are more likely to suffer illness months later
- High blood pressure
- Increasing stroke & heart attacks
- Reduced fertility
Why we evolved to get acute and chronic stress?
Acute Stress:
- Helps animals to respond to threats to their survival “flight or flight”
- A reactive/reflexive brain might improve survival in immediate danger.
Chronic Stress:
- Effects of early stress on an individual are clearly negative – leading to increased antisocial behaviour, aggression and/or social isolation.
- In an evolutionary context, some have suggested that these sustained changes could prepare an animal/human for similar adversity later in life (enhance fighting readiness)
What other factors (other than control) influence the stress response
- Genetics
- Environment
Examples:
Hot environmental temperatures linked to higher crime and violence (“hot under the collar”)
Financial crises leads to high levels of violence against women and children.
What is PTSD caused by?
What are other factors?
What is it associated with?
Cause
- Experiencing or witnessing death/serious harm (actual or threatened) or learning of trauma to loved one
Factors
- Both environmental and genetic factors
Associated with
- Recurrent dreams, panic attacks &“flash backs”.
- Poor mental and physical health
What are the brain areas associated with PTSD?
- Smaller hippocampus (Twin war veteran)
- Increased amygdala and insula activity to threat
- Reduced vmPFC to threat
- Similar pattern to chornic stress: Less PFC, more Amygdala
Stress and Psychiatric Disorders - Depression, SZ/Bipolar, AD
Depression
- Similar brain areas are implicated in chronic stress and depression and while depression is different it is often considered a stress-related disorder
SZ/Bipolar
- Triggers increased severity of symptoms
AD
- Women with serious stressors in middle age more likely to develop memory impairments
How does stress affect emotional memory neurologically
- Glucocorticoid (e.g. cortisol) stimulates NA response in the basolateral nucleus of the amygdala (BLA), enhancing retention of emotional stimuli
- Stress hormones (Cortisol and NA) have been associated with greater memory consolidation in animal and humans
How does propranolol work?
Propranolol
- NA enhances emotional memory
- Propanolol block activation of β-adrenergic receptors by NA and adrenal stress hormones, inhibiting NA action
- Triggering memory + propanolol = Memories can be "relearened" without fear response, with original memory intact (Implications for PTSD and anxiety-related conditions)
What is MBSR. How does it help?
MBSR: Mindfulness-Based Stress Reduction
- MBSR found to moderately (compared to controls/placebo) improved depression, anxiety, distress, stress, quiality of life
How?
- Increasing cognitive flexibility and tolerance for uncomfortable physical stress/anxious sensations
- Reduce perception of threat
Explain the brain-behaviour cycle of stress
- Early life stress (Life circumstances) >
- "Epigenetic changes' >
- Lasting biological changes >
- Impair decision making and health
- More negative behaviour and life circumstances
What is fear conditioning a form of and what does it involve?
- Classical conditioning
- Pairing aversive stimulus (US; Shock) with neutral stimulus (CS; Light)
- Original neutral stimulus (CS; Light) leads to fear response (CR)
What is classical and operant condiioning. Similarity/Differences
Classical:
- Associating automatic involuntary behaviour and stimulus
- Neutral stimulus before reflex
Operant:
- Associating voluntary behaviour and consequence
- Apply reinforcement or punishment to strengthen or weaken behaviour
What is fear extinction?
Gradual reduction of fear response when the conditioned stimulus is repeatedly presented without aversive outcome
What are three properties of fear extinction?
- Fear extinction requires extensive traning and fragile, unlike fear conditioning (rapid and robust)
- Spontaneous Recovery: Time
- Renewal: Context
- Reinstatement: Re-exposed to original US
- Fear extinction is context-dependent
- Learning to reduce fear in one context may not translate to another
- Fear extinction produces new memory trace (CS without aversive outcome), inhibiting original CS-US fear association
- Not erase, but inhibit
What are typical procedures in animal studies of fear conditioning/extinction
1.) Conditiong acquisiton phase
- Light/tone is paired with shock
2.) Extinction phase (Different chamber for context)
- Presented with repeated trials of light without shock
3.) Test Phase
- Subsequent day to assess retention of extinction
From Rodent Studies, How is fear conditioned in the brain (Neurologically)?
- Sensory input (CS) from auditory/visual cortex pairs with pain signals (US) from somatosensory cortex in basolateral nucleus of amygdala (BLA)
- Conditioned association from BLA activates central nucleus of amygdala
- Central nucelus of amydala sends afferent to hypothalamic and midbrain regions controlling arousal, freezing, hormonal response.
Difference between low and high road
Low Road:
- Autonmatic, rapid, reflexive fear response
- Senory input > thalamus > amygdala
High Road:
- Slower cortical inhibitory response
- If determined not threatening, PFC in high road inhibits fear response
What are the key areas in fear in RODENTS
Prelimbic Cortex (PL)
- Stimulation increase fear and inactivation reduces fear
- Activity predicts poor extinction
- dACC equivalent
- Fear conditioning
Infralimbic Cortex (IL)
- Stimulation reduces fear and inactivation impairs extinction
- Activity predicts good extinction
- vmPFC equivalent
- Fear extinction
Hippocampus
- Contextual information
- Work with vmPFC to inhibit amygdala
What does human neuroimaging found in regions for fear conditioning, extinction and extinction recall studies?
Conditioning
- dACC: Threat appraisal
- Insula: Introspective awareness of fear
Extinction
- dACC & Insula (note: there is activity but they are being inhibited)
- vmPFC (but less roboust)
Extinction Recall
- dACC & Insula (note: there is activity but they are being inhibited)
- vmPFC and hippocampus if compare CS+ (extinguished) to CS+ (never extinguished)
fMRI did not see Amygdala
SIMILAR REGIONS
Why do we see similar activations in conditionding and extinction in fMRI?
- Dorsal ACC and anterior insula are involved in threat appraisal and experience of anxiety. These same networks might be activated in conditioning and extinction but perform different functions
- Alternatively, these networks might still be activated but no behavioural experience/evidence of conditioning – a dissociation in fear measures
- Role of vmPFC in extinction still debated – contextual processing rather than fear inhibition?
- Maybe due to level of threat in healthy controls?
According to meta-analysis of fear extinction studies, what is the difference between humans and rodents neurologically
Compared to rodents, humans have
- Less robust vmPFC activation
- More robust dACC and anterior insula (similar to fear conditioning)
What are 3 explanations as to a lack of amygdala activity in human fear conditioning studies?
- Resolution of fMRI
- Can't image subnucleii of amygdala
- Amygdala only recruited with intense threat as part of defence-circuitry response (mild anxiety in human studies)
- Amygdala response habitutate after repeated trials
Why are three explanations fear conditioning and extinction involved in etiology of anxiety disorders
- Greater conditionability of CS + of anxetiy disorders (Note this is wrong)
- Greater stimulus generalization
- Greater Reactivity to CS+ and Generalization to CS-
- Impaired capacity to inhibt fear to CS+
When compared healthy and anxious participants in fear conditioning and extinction task, what were the results
- Greater conditionability of CS + of anxiety disorders
- No Difference
- Greater stimulus generalization
- Greater Reactivity to CS+ and Generalization to CS-
- Overgeneralization in anxious patients
- Impaired capacity to inhibt fear to CS+
- Reduced vmPPFC activity during extinction recall (another study) as well
What are results of fear conditoning/extinction task with Trauma-exposed vs PTSD
Compared to Trauma-exposed controls,
- No greater conditionability in PTSD
- Impaired fear extinction in PTSD
- Increased amygdala activity during extinction recall
- Reduced vmPFC activity during extinction recall
- Note: Extinction recall is stronger than extinction learning
What is the link between PTSD symptoms and extinction? What is an evidence?
- 10-15% who develop long-term PTSD have impaired extinction post-trauma (and pre-trauma)
- Deficits in extinction networks (reduced vmPFC) and increase amygdala activity to threat is normalized after exposure therapy for PTSD (i.e. increase vmPFC; decrease amygdala activity)
Why study sex hormones? (4)
- Sex hormones have a profound effect on development in the brain and body with important changes across the lifespan (neonatal, puberty, pregnancy in women, older age)
- They play a critical role in glial and neuronal development, brain structure and function
- They affect the quality of cognition and mood
- There play a role in psychopathology and mental health disorders
Anxiety disorders rates and gender
- Women develop anxiety/stress-related disorders 2x the rate of men (not substance use disorder)
- Prevalance rates equal in boys and girls, increased prevalence develops at puberty with sex hormones increase, gender difference reduces post-menopause
- Suggest sex hormones' role in psychopathology
Even though it's important to study sex hormones, why are there so few studies?
- More expensive having male and female samples
- More expensive to control menstrual phase
What are the main sex hormones
1+2.) Estrogen and Progestrone "Female"
- Released from ovaries
- Flucuates across menstrual cycle
- Increases in pregnancy
- Drop post-pregnancy and post-menopause
- Females have testosterone (at low levels) from ovaries
3.) Testosterone "Male"
- Released from testes
- Males have estrogen (at lower levels) converted from testosterone
Both men and women have "male" and "female" sex hormones (with individual differences)
What explains gender differences?
- Exposure to sex hormones both before and after birth (some coded by non-sex chromosomes) required for sexual dimorphism (different characteristics)
- Importance of
- gender roles
- environmental influences
- culture
How does sex hormones impact the brain. Elaborate more on estrogen and progesterone
- Interacts directly with nervous system
- Estrogen and progesterone
- Brain development and synaptic plasticity
- Influence activity of main NT systems and can directly affect NT receptor function
What is the trend of sex hormones across the lifespan
Males
Puberty: Marked increase in testosterone, slight increase in estrodial
Females
Puberty: Marked increase in estrodial, no increase in testosterone
Menopause: Marked reduction in estrodial
What happens to hormones at puberty.
Explain the neurological process.
- Hypothalamus and pituitary gland involved in release of sex hormones
- GNRH (gonadal-releasing hormone) in the pituitary gland stimulate luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to stimulate the respective reproductive organs (testes and ovaries)
- >>> Male testes and female ovaries release testosterone (sperm) and estrogen (egg) respectively
Sex hormones and the menstrual cycle
Start Cycle (day 1-7)
- Estrogen and progesterone are low.
Mid Cycle (day 14)
- Progesterone stay low.
- Increases estrogen to peak stimulating LH and FSH
- LH and FSH spikes at midcycle (day 14) in preparation for ovulation
- After that, estrogen, LH, FSH drops
Luteal (day 18-24)
- Increase in progesterone and a small increase in estrogen
- Progesterone levels remain low until now
- Causes breakout phase
Goes down during menstration
Gender differences and behavior in children.
Girls: likes toys that allow nurturance and social play
Boys: likes toys that are more active
- Unclear how much is nature / nurture
- But at 1 day old, boys look at mobile while female look at faces
- Male monkeys play with cars/balls while female monkeys play with dolls
What is testosterone associated with, and what should it be conceptualised as?
- T is associated with social aggression and response to social challenges
- E.g., Male chimps release T and are more aggressive when female chimps in reproductive phase
- T should not be conceptualized in terms of gender but instead in terms of Competition (high T) & Nurturance (low T)
What are gender differences in relation to violence?
- Offending rates consistently higher for men, but divergence in offending rates between genders (where male increase substantially) coincides with puberty.
- Role of Testosterone in violence
Depending on the offence, men often over-represent victims of violence (male vs male fighting) but are also frequently impacted by domestic violenc. But the predominant victims of domestic violence are women.
What is estrogen involved in?
- Social Behaviour
- Higher levels of estrogen linked to better mood, improved memory and executive function
- Administration of estrogen can bias decision-making toward smaller, more accessible goals
What is the difference betweeen hormones and pheromones
- Hormones transmit messages from one part of the body (the secreting gland) to another (the target tissue).
- Pheromones are chemicals that carry messages from one animal to another. Released from one animal that directly affect the physiology or behaviour of another (normally detected by smelling)
When exposed to a chemical found in men’s sweat, what do women report?
Women reported
- Alertness
- Psitive mood
- Icreased sexual arousal
- Timing of their menstrual cycle was altered
- When participating in a speed dating experiment women rated men to be more attractive.
Men reported less positive mood.
Depression and Sex Hormones (3)
- Depression is 1.5 – 3 times more prevalent in women (prior to puberty the numbers are equal)
- Periods of hormonal transitions and elevated or fluctuating sex hormones are associated with increased mood-disturbances
- Correlation between suicide attempts and periods of low estrogen
What is the link betwenen hormonal contraception and depression (3)
- Compared with non-users, contraceptive users had greater risk of requiring anti depressants and receiving depression diagnosis
- Contraceptives with greater progesterone showed greatest risk increase.
- Greatest impacts were seen in adolescents (15-19yrs) with use of the pill increasing anti-depressant use by 80%
What is post-partum depression and how are sex hormones related?
Post-partum depression: Onset of depressive symptoms after the birth of a baby.
- Genetic vulnerability
- Change in hormone levels (dramatic drop)
- High stress (lack of sleep etc.)
- Lack of support
May contribute
3 levels: Blues, Depression, Psychosis
What is the link between anxiety disorders and sex hormones, and PTSD
- Anxiety disorders are also 1.5 to 2x greater prevalence in women than men (Only after puberty)
- Low estradiol associated with impaired fear extinction recall and PTSD
What is the link between schizophrenia and sex hormones
- Generally emerge during late adolescence and early adulthood for males and females
- Low levels of Testosterone also linked to reduced mood, depression and impaired concentration, reduced confidence.
