BIOPSY 215 - FInal Exam (NEW MATERIAL)

learning

process of aquiring new knowledge

memory

expression of the knowledge you’ve learned

• change in behavior based on experience

difference between learning and memory

learning is acquiring knowledge; memory is storing and expressing it

classical conditioning

• forming associations between stimuli that changes reponse to one of the stimuli

• associated with Ivan Pavlov

  • a bell paired with food caused dogs to salivate to the bell alone

key parts of classical conditioning

• unconditioned stimulus (US): naturally causes a response

• unconditioned response (UR): natural response to the US

• conditioned stimulus (CS): learned stimulus

• conditioned response (CR): learned response to CS

types of operant conditioning

• reinforcement: increase probability of future responses

• punishment: decreases probability of future responses

• positive: something is given/added

• negative: something is taken away/removed

flow of information through memory

1. sensory memory

2. short-term memory (STM) / working memory

3. long-term memory (LTM)

what biological changes are associated with short term vs. long term

• short-term/working memory:

  • based on synaptic transmission

  • temporary changes in neural activity

• long-term memory:

  • involved gene expression and protein synthesis

  • long-lasting synaptic changes

short term memory

brief storage of information

working memory

• actively manipulates while holding it in mind

  • example: digit span test (used for both STM and WM)

capacity

• memory systems have limited capacity, especially short-term memory

chunking

• grouping information into meaningful units to increase capacity of STM and WM

primary effect

better recall of items at the beginning of a list

recency effect

• better recall of items at the end of a list

types of long term memory

• explicit (declarative) memory

  • episodic: personal experiences and events

  • semantic: facts and general knowledge

• implicit (non-declarative) memory

  • procedural: skills, habits

  • priming

  • associative learning

  • non-associative learning

hippocampus

• declarative memories (especially episodic)

• patient H.M. evidence:

  • removal of hippocampus caused: severe anterograde and retrograde amnesia

  • intact abilities: working memory, language and intelligence, implicit memory

trisynaptic circuit

1. entorhinal cortex

2. perforant path

3. mossy fibers

4. schaffer collaterals

5. exit hippocampus

spatial memory

• hippocampus is involved in spatial navigation

• london taxi driver study

  • posterior hippocampus increase

  • anterior hippocampus decrease

  • shows plasticity from navigation experience

place cell

• neurons that fire when an animal is in a specific location, creating spatial maps

prefrontal cortex (PFC) & Memory

• heavily involved in working memory

• two pathways

  • direct pathway: posterior parietal cortex —> PFC

  • indirect pathway: posterior parietal cortex —> thalamus & basal ganglia —> PFC

striatum role in memory

• made up of caudate, putamen, and nucleus accumbens

• important for habit-forming, motor learning, associative learning

• linked to dopamine

• NAc is important for reward learning

• increased striatum activity during habitual behaviors; implicit memory

types of memory for other brain areas - amygala, anterior cingulate cortex

• amygdala - fear learning

• anterior cingulate cortex - reward learning

steps of long-term potentiation (LTP)

1. glutamate release presynaptically

2. glutamate binds AMPA receptors

3. EPSP occurs

4. Mg2+ block removed from NMDA receptor

5. Ca2+ enters the postsynaptic cell

6. Ca2+ activates PKC and CaMKII

presynaptic effects of LTP

• increase in neurotransmitter release

• responding to retrograde transmitters

postsynaptic effects of LTP

• phosphorylation of AMPA receptors

• new AMPA receptors added to membrane

• increase in GluR1-containing AMPA receptors

• growth of dendritic spines

what is LTD

• weakening of synaptic connections

• occurs following prolonged low level of synaptic stimulation

• mechanism

  • removal/endocytosis of AMPA receptors

  • dephosphorylation of AMPA receptors

korsakoff’s syndrome - biological cause

• symptoms:

  • similar to PFC damage

  • confabulation - fill in gaps of memories by guessing

• cause:

  • thiamine (vitamine B1) deficiency

  • loss of neurons, especially in dorsomedial thalamus

alzheimer’s disease - biological cause

• one of the most common causes of memory loss

• symptoms:

  • memory problems (especially declarative memory); may fluctuate

  • confusion

  • depression

• cause:

  • amyloid-β protein

  • tau protein

  • genetics

    • APOE gene - APOE4 associated with higher risk

  • brain atrophy

what does morris water maze test?

• the morris water maze tests spatial learning and spatial memory, which are hippocampus-dependent

• animals must learn the location of a hidden platform using external visual cues

• key measures:

  • latency

  • path proximity

  • time spent in the target zone

• poorer performance = worse spatial learned/memory

• used because hippocampal neurogenesis is strongly linked to spatial navigation

what is TMZ and how does it affect the brain

• TMZ (temozolomide) is a chemotherapeutic drug

  • used to suppress adult hippocampal neurogenesis

• TMZ works by:

  • preventing cell division

  • reducing the birth of new neurons in the dentate gyrus of hippocampus

what is BrdU/what does it allow you to test

• BrdU is a compound that gets incorporated into DNA during cell division

• it labels newly generated cells

• in this study, BrdU was used to

  • measure the amount of neurogenesis

  • confirm that TMZ successfully reduced new neuron formation

• BrdU-positive cells = evidence of recent neurogenesis

general findings: depleting neurogenesis affected learning in which age group

• significant impairment in juvenile animals

• middle-aged: little to no effect

• adults: moderate effects

james-lange theory

• physiological response comes first, and the emotion is the interpretation of that response

  • example: I am afraid because my heart is racing

cannoon-bard theory

• physiological arousal + emotional experience occur simultaneously

  • example: I fear and my heart races at the same time

schachter-singer theory

• emotion results from:

  • physiological arousal

  • cognitive appraisal (interpreting the situation/context)

• example: heart racing + dangerous context = fear

this theory explicitly includes cognition

basic emotion theory (BET)

• core concepts

  • limited set of innate emotions

  • different brain regions/circuits are responsible for different emotions

  • strong background in evolutionary approach

basic emotions of basic emotion theory (BET)

1. happiness, sadness, fear, anger, disgust, surprise

think of inside out

theory of constructed emotion (TCE)

• emotions are NOT innate

• constructed in real time by the brain using:

  • affect

  • context

  • past experiences and memories

• no emotion has a single dedicated brain area

what emotion is the amygdala associated with?

• associated with fear and anxiety

amygdala connections (theres four)

• amygdala —> hypothalamus: autonomic fear responses

• amygdala —> PFC: approach and avoidance behaviors

• amygdala —> pons: startle reflex

• BNST —> amygdala: generalized emotional arousal

how does behavior change with damage to the amygdala?

1. no modification of startle reflex

2. difficulty interpreting emotional stimuli

3. difficulty with fear learning/show “fearlessness”

key symptoms/diagnostic of generalized anxiety disorder (GAD)

• excessive worry for at least 6 months

• difficulty controlling the worry

• associated with symptoms like:

  • restlessness

  • fatigue

  • difficulty concentrating

  • muscle tension

  • sleep disturbance

  • irritability

• causes significant distress or impairment

key symptoms/diagnostic of panic disorder

• recurrent, unexpected panic attacks

• at least one attack followed by:

  • persistent concern about future attacks

  • maladaptive behavior change

key symptoms/diagnostic of specific phobia

• intense fear or anxiety about a specific object or situation

• immediate anxiety response

• actively avoided or endured with distress

• fear is out of proportion

• lasts for at least 6 months

key symptoms/diagnostic of post traumatic stress disorder (PTSD)

• exposure to traumatic event

• 4 symptom categories

1. intrusion/re-experiencing

2. avoidance

3. negative mood/cognition

4. hyperarousal/hyperreactvity

• symptoms last at least 1 month

key symptoms/diagnostic of obsessive-compulsive disorder (OCD)

• obsessions: intrusive thoughts, urges, images

• compulsions: repetitive behaviors or mental acts

• performed to reduce distress

• time-consuming or impairing

general neurobiological correlates of anxiety and related disorders

• sympathetic nervous system dysregulation

• altered HPA axis function

• neurotransmitter changes:

  • GABA - decrease

  • norepinephrine - decrease OR increase

animal research models of anxiety - open field test

• more time in center —> less anxiety

animal research models of anxiety - elevated plus maze

• more time in open arms —> less anxiety

animal research models of anxiety - light-dark box

• more time in light area —> less anxiety

treatments of anxiety - benzodiazepines

• positive allosteric modulator of GABAa receptor

• has potential for dependence, withdrawal symptoms; better for SHORT-TERM treatment

treatments of anxiety - SSRI

• selective serotonin reuptake inhibitors

• block serotonin transporters

kratom - does it increase or decrease anxiety? what 3 neurotransmitter systems is it working through?

• generally decreases anxiety (anxiolytic-like effects)

• acts on three neurotransmitter systems:

1. opioidergic system

2. GABAergic system

3. dopaminergic system

kratom - what is the rationale of using agonists and antagonists for certain receptor systems to test the mechanisms for a drug where mechanisms are unknown?

• researchers use agonists and antagonists to see whether blocking or mimicking specific receptors eliminate the drug’s effect, revealing which systems are involved

core categories of symptoms (4 DSM-5 subcategories)

• impaired control

  • using more than intended

  • difficulty cutting down or stopping

  • craving

• social problems

  • problems at work, school, or home

  • continued use despite social/interpersonal issues

• risky use

  • using in physically dangerous situations

  • continued use despite harm

• physical dependence

  • tolerance

  • withdrawal

general substance use disorder mechanisms - what changes occur? (mesolimbic pathway, NAc, dopamine, cravings)

drugs increase dopamine in the VTA —> NAc

• NAc is responds less to reward but responds more to drug rewarded-associated cues over time

  • causes craving and compulsive cues

cycle of substance use disorder - 3 stages

1. binge/intoxication

2. negative affect/withdrawal

3. preoccupation/anticipation (craving)

synaptic mechanisms of action for drug classes - stimulants

increase dopamine signaling:

• cocaine - blocks dopamine, serotonin, norepinephrine transporters

• amphetamine - reverse DA transporter (shifts DA from vesicles to cytosol)

• nicotine - nicotinic acetylcholine receptor agonist

synaptic mechanisms of action for drug classes - opioids

opioid receptors agonists:

• mu - pain relief, euphoria

• delta - pain relief, reduce anxiety

• kappa - pain relief, feeling of dysphoria

synaptic mechanisms of action for drug classes - alcohol

• positive allosteric modulator of GABA receptors

• antagonist at NMDA receptors

synaptic mechanisms of action for drug classes - cannabinoids

cannabinoid receptor agonists

• suppress GABA and glutamate through retrograde signaling and inhibition of vesicle release

synaptic mechanisms of action for drug classes - hallucinogens

serotonin receptor agonists (LSD, psilocybin, MDMA, ketamine)

FDA-approved treatments for SUD treatments - alcohol

• disulfiram/antabuse - affects alcohol metabolism

• acamprosate - partial agonist at NMDA receptors

• naltrexone - opioid receptor antagonist

FDA-approved treatments for SUD treatments - opioid

• methadone/buprenorphine - opioid receptor agonists

• naltrexone - opioid receptor antagonist

major depressive disorder

• 5 or more symptoms for at least 2 weeks

  • must include depressed mood or anhedonia

bipolar disorder - difference between bipolar I and bipolar II

• bipolar I - manic & depressive episodes

• bipolar II - hypomanic & depressive episodes

general mechanism of action for lithium

mood stabilizer that INHIBITS inositol monophosphatase, DECREASE second-messenger signaling, INCREASE GABA, and DECREASE dopamine and glutamate

4 main categories of pharmaceutical treatments for depression & their mechanisms of action

1. tricyclics - block serotonin, norepinephrine, and dopamine transporters

2. SSRIs - block serotonin transporters

3. SNRIs - block serotonin and norepinephrine transporters

4. MAOIs - inhibit monoamine oxidase

all lead to the monoamine hypothesis

what is the monoamine hypothesis of depression?

• depression results from low monoamine neurotransmitters

• limited scientific support

treatment methods for treatment-resistant depression - electroconvulsive therapy (ECT)

induces controlled seizures under anesthesia, producing rapid antidepressant effects by increasing neuroplasticity and BDNF

treatment methods for treatment-resistant depression - transcranial magneitc stimulation (TMS)

noninvasive treatment that uses magnetic pulses to stimulate cortical brain regions and alter mood-related neural circuits

treatment methods for treatment-resistant depression - ketamine & esketamine

NMDA receptor antagonist that rapidly increase synaptic plasticity and BDNF, leading to fast antidepressant effects

treatment methods for treatment-resistant depression - psilocybin

serotonin receptor agonist that disrupts rigid thought patterns and promotes lasting changes in brain connectivity and plasticity

how do treatments for treatment-resistant depression generally work?

• they modulate neural activity and enhance neuroplasticity and BDNF rather than acting slowly through monoamine neurotransmitter alone

what role might neuroplasticity and BDNF play in depression?

BDNF enhances LTP

• treatments that increase BDNF and plasticity provide faster symptom relief

schizophrenia - diagnostic criteria

• at least 2 or more symptoms for at least 1 month

  • delusions

  • hallucinations

  • disorganized speech/behavior

  • negative symptoms (alogia, avolition, flat affect)

schizophrenia - positive vs negative symptoms

• positive: delusions, hallucinations, disorganized behavior

• negative: flat affect, avolition, alogia

schizophrenia - neurodevelopmental hypothesis

prenatal and/or neonatal brain abnormalities combined with genetic and environmental risk factors contribute to later schizophrenia

• genetic contribution

  • heritable with no single cause

  • DISC1 is implicated in neuronal migration, differentiation, learning, and dendritic spines

• environmental risk factors

  • urban living

  • prenatal stress or illness

  • pregnancy/birth complications

  • season of birth effects increase risk

schizophrenia - dopamine hypothesis

schizophrenia results from excess activity in certain brain areas

schizophrenia - glutamate hypothesis

deicient or dysregulated glutamate activity causes schizophrenia

antipsychotics

block dopamine receptors; based on the dopamine hypothesis that excess dopamine contributes to schizophrenia

second-generation antipsychotics

strongly block serotonin receptors & increase glutamate signaling

• align with the glutamate hypothesis of schizophrenia

autism spectrum disorder - diagnostic criteria

• persistent deficits in social communication/interaction

• restricted, repetitive behaviors, interests, hyper- or hypo-reactivity

autism spectrum disorder - core social deficits

• social-emotional reciprocity

• nonverbal communication

• developing/understanding relationships

autism spectrum disorder - restricted and repetitive behaviors

• stereotyped movements or speech

• inflexible routines

• highly restricted interests

• abnormal sensory reactivity (hyper- or hypo-)

autism spectrum disorder - neurodevelopmental changes associated

• altered somatosensory processing

• reduced GABA signaling

• local & global hypoconnectivity

• inefficient synaptic pruning