Exam 4 Flashcards
cycles occur everywhere
- rhythms
- eating and drinking
- light (color is based on frequency and brightness is based on amplitude)
- neuroendocrine feedback
- sleeping
how does our body know when to sleep and when to be awake?
- light from sun entrains our sleep wake cycle
- day and night cycle occurs over 24 hours
- thus, our sleep wake cycle is set to 24 hours
- specific parts of the brain are activated by light and produce proteins during the day but not at night
- the neuroendocrine system is also important as it releases melatonin from the pineal gland
- melatonin is high at night but low during the day
pineal gland
releases melatonin into blood stream
melatonin induces sleep…
by receiving information from the suprachiasmatic nucleus (SCN) of the hypothalamus
SCN receiving light information
- information from the retina is sent via the optic tract to the thalamus (what nucleus)
- optic tract sends a small set of axons that synapse to the SCN
- information sent by these ganglion axons do not rely on photoreceptors
- ganglion cells of the retina contain a receptor called melanopsin, which is activated by blue light
- information is sent to the SCN by glutamate release from ganglion axon terminals
- release of glutamate activates SCN neurons and results in production of new proteins
retinal ganglion cells…
contain melanopsin and project light information to SCN
melanopsin
most sensitive to blue light
behavioral changes in animals
caused by light
specific genes and proteins are made in SCN
caused by light
specific genes in SCN are activated
caused by light
light activates specific genes in the SCN
- SCN cells in mammals make the proteins clock and cycle
- clock and cycle proteins bind together to form a dimer
- the clock/cycle dimer promotes transcription of 2 genes: period (per) and crypochrome (cry)
- proteins arising from per and cry bind to each other and to a third one, tau
- the per/cry/tau protein complex enters the nucleus and inhibits the transcription of per and cry
- no new proteins are made until the first set degrades and the cycle begins again approximately every 24 hours
molecular/genetic events of cyclic activity regulating sleep
- proteins clock and cycle binds together, forming dimer
- clock/cycle dimer binds to DNA, enhancing transcription of genes for per and cry
- per and cry bind together as complex that inhibits activity of clock/cycle dimer, slowing transcription of per and cry genes, and therefore slowing production of per and cry proteins
- per/cry proteins eventually break down or are modified so they no longer inhibit clock/cycle, allowing the process to start again; this cycle of gene transcription, protein interactions, and inhibition of gene expression takes about 24 hours to complete
- retinal ganglion cells detect light with melanopsin, and their axons in the retinohypothalamic tract release glutamate onto neurons in the SCN; the glutamate stimulation leads to increased transcription of the per gene, synchronizing/entraining the molecular clock to the day-night cycle
EEG measures cyclic brain activity
- EEG measures change in membrane potential (mV) over time (mSec)
- EEG measures thousands of neurons and their activity
- this activity is the avg of EPSPs, IPSPs, and action potentials
- the result comes in the form of brain waves called the “field potential”
- field potentials are cyclic (fluctuate up and down)
- cycle can be fast or slow, high or low (amplitude and frequency)
2 classes of sleep
slow-wave sleep (SWS):
- divided into 4 stages and is characterized by slow-wave EEG activity
rapid-eye-movement sleep (REM):
- characterized by small amplitude, fast-EEG waves, no postural tension, and rapid eye movements
dreaming
- occurs during SWS and REM
- during SWS events you experience during the day are replayed (replay is equal to how fast they occur in life)
- during REM replay also occurs, but replay is 10x faster than the experience
- dreaming induces memory consolidation and problem solving
stage 1 sleep
- shows waves of irregular frequency and smaller amplitude called sharp waves
- heart rate slows, muscle tension reduces, eyes move about
- lasts several minutes
stage 2 sleep
- defined by waves of 12 to 14 Hz that occur in bursts, called sleep spindles
- K-complexes appear (sharp negative EEG potentials)
stage 3 sleep
- continued sleep spindles
- defined by the appearance of large-amplitude, very slow waves called delta waves
- delta waves occur about once per second
stage 4 sleep
- delta waves are present about half the time
REM sleep
- active EEG with small-amplitude, high-frequency waves, like an awake person
- muscles are relaxed (called paradoxical sleep)
human sleep patterns change with age
- amount of REM sleep severely declines after one is no longer an infant
- amount of non-REM sleep also decreases with age
several regions regulate sleep/its different parts
- lesion experiments showed that diff sleep systems originate in diff parts of the brain
- lesions between the medulla and spinal cord showed signs of sleep and wakefulness, providing evidence that the change of sleep to wake is in the brain
brain is responsible for sleep wake cycle
transection of lower brainstem produces an isolated brain, which exhibits signs of alternating between wakefulness, SWS, and REM sleep, showing that systems controlling sleep are found in the brain
SWS is produced by forebrain
transection of brainstem at midbrain produces an isolated forebrain, which exhibits signs of constant SWS, showing that a forebrain system promotes SWS and that brainstem promote wakefulness and REM sleep
pons
induces REM
SCN
initiates beginning of sleep through light
forebrain
produces SWS
universal facial expression of emotion
anger sadness happiness fear disgust surprise contempt embarrassment
universal facial emotions
- there is cross-cultural similarity in expression
- the extent of cultural influence in under debate
adrenal glands
corticosteroids and norepinephrine and epinephrine are stress hormones
HPA axis (draw)
–
how does the emotional and physiological tie into the brain?
- the neuroendocrine axes
- areas within brain that produce neurotransmitters known to increase or decrease on physiological/emotional state (example: dopamine is released from VTA when reward is encountered)
brain self stimulation of reward center
- rats have an electrode placed into the midbrain
- these electrodes target medial forebrain bundle (large bundle of axons)
- these axons stem from the VTA and the substantia nigra, the primary regions of the brain that produces the neurotransmitter dopamine
reward activation
- you get an unexpected reward (you win art contest)
- you interpret the info and find that winning an art contest is good
- you feel rewarded, relaxed, excited, happy, etc.
- your interpretation adds to these feelings and you are positively reinforced
- reinforcement occurs and leads you to repeat behaviors that got you to unexpected reward
drug addiction
- you get an unexpected reward (you smoke methamphetamine)
- you feel rewarded, excited, happy, physically satisfied, euphoric, etc.
- these physiological responses allow you to interpret this as very good
- the physiological reactions and interpretation add together
- reinforcement occurs and leads you to repeat behaviors that got you to unexpected reward
- repeat, repeat, repeat and drug addiction can occur
fear
classical conditioning can elicit fear:
- by pairing a stimulus with an aversive stimulus, like shock
- eventually the first stimulus by itself can produce fear, including freezing and autonomic changes
pavlovian conditioning/classical conditioning
CS - bell
US - meat
UR - salivation
CS+US –> CR
CR - salivation
tone fear conditioning
- a type of classical conditioning
CS - tone
US - shock
CR and UR - freezing
- this type of memory requires the amygdala because both shock and the time end at the same time
- however, if there is some time (30sec) between the end of the tone and the shock (trace), then this type of learning requires the hippocampus
amygdala
- important for emotional learning and memory
- stress is good but too much is bad
- chronic stress can lead to overactive amygdala
- overactive in general anxiety disorder (non threatening stimuli feel threatening)
- those with anxiety are often depressed
the circuitry of fear (draw)
–
process of fear response
- see scorpion
- visual info enters eyes, travels to LGN, via optic radiation it goes to V1 (visual/sensory info can travel straight from the thalamus to the amygdala)
- from V1 info is processed in the what and where pathways
- that info integrates in the hippocampus for memory formation
- hippocampus sends info to the amygdala about the environment
- amygdala integrates sensory info of fearful event with the context - classical conditioning
3 types of emotional responses are evoked
- central gray/periaqueductal gray pathway - emotional behaviors (freezing)
- lateral hypothalamus pathway - autonomic responses (blood is redirected to muscles)
- bed nucleus of stria terminalis pathway - hormonal responses (release of stress hormones)
stress
- stress includes stress stimuli, processing, and stress responses
- the alarm reaction is the initial response, followed by the adaptation stage
- the exhaustion stage is the reaction to prolonged stress
- chronic stress can lead to anxiety, depression, PTSD, weight gain/loss, illness
- under stress, the hypothalamus produces CRH
- CRH causes release of ACTH leading to cortisol release
- growth hormone, epinephrine, and norepinephrine are also released
autonomic activation during a jump
hormonal responses:
- thyroid, adrenal glands, testes
endocrine responses:
- cortisol, testosterone, epinephrine, norepinephrine, growth hormone
parasympathetic responses:
- heart, liver, testes, bladder, intestines
sympathetic responses:
- spleen, adrenal glands, pancreas, heart, liver, intestines
hormonal changes in humans in response to social stresses
epinephrine increases in crowds
facial feedback hypothesis
- several studies indicate that when people are manipulated into mimicking facial expressions of sadness or happiness, their emotional mood is actually affected
- so putting on a happy, cheerful expression may actually help you to feel better
brain self-stimulation sites in rodents
animals will work very hard pressing a bar to receive mild electrical stimulation at any of these sites:
- basal forebrain, nucleus accumbens, MFB, septum, ventral midbrain, VTA, substantia nigra, locus coeruleus, dorsal brainstem
- VTA sends dopaminergic axons to the nucleus accumbens
changes in dendritic spines during fear conditioning
decrease in dendritic spines during fear conditioning
factors that interact during the development and progression of disease
stressors:
- social stress, microbes, toxins, impaired nutrition
body defense system:
- immune system, genetic factors, endocrine factors, nervous system, memory and perception, coping/appraisal strategies
HM
- suffered from debilitating seizures
- underwent an operation to remove medial temporal lobe
- MTL contains crucial structure for memory consolidation (hippocampus)
hippocampus is necessary for episodic memory consolidation
- memories of the remote past remained with HM after his surgery
- memories of the past that were close in time to his surgery were gone (retrograde amnesia)
- working and short term memories are still intact
- STM did not become LTM (anterograde amnesia)
- the hippocampus is crucial in strengthening memories, which is also known as memory consolidation
anterograde amnesia
inability to create new long term memories
retrograde amnesia
inability to remember memories that occurred before the trauma
memory circuit
memory begins with sensory inputs; from vision to hippocampus
skill learning forms memory of movement, not of events
mirror-tracing task:
- by third day of doing task HM was making no mistakes but had no memory of doing the task previously
basal ganglia
necessary for procedural learning
taxonomy of memory (draw)
–
episodic memory
what did I eat for breakfast (requires hippocampus)
semantic memory
what is the capital of Spain
working memory
what did I just say
priming
subliminal advertising (repetition priming - change in stimulus processing due to prior exposure to the stimulus)
procedural memory/skill learning
how to ride a bicycle (learning to perform a task requiring motor coordination) - requires basal ganglia
conditioning
phobias
differentiation of memories
shows that:
- memory isn’t just one big storage area
- memories must rely on different brain regions
unification of brain to memory shows…
that complex cognitive functions rely on neuronal activity –> therefore we should be able to study sets of neurons within the hippocampus and how they underlie memory formation
time scale of memory
sensory: - time it takes for sensory info to travel to processed regions (milliseconds to seconds) working: - tens of seconds to a few minutes STM: - days, weeks, months LTM: - years, decades, your life time - 2 types: recent (months/years) and remote (decades)
hippocampus and memory consolidation
- memory consolidation is strengthening of newly learnt memories
- some memories are consolidated and others are not
- consolidation takes time and the process requires new DNA and protein production
- hippocampus undergoes memory consolidation and turns STM into LTM
- very old memories that were first created in hippocampus eventually move to cortex
- STM and recent LTM are in hippocampus and remote LTM is in cortex
- hippocampus transfers info slowly into cortex over years (while one is asleep probably)
synaptic plasticity
- studied extensively in rodent hippocampus
- LTP can be induced at the perforant path-dentate gyrus synapse and the CA3-CA1 synapse
LTP artificially induces synaptic plasticity
synapses in LTP behave like Hebbian synapses:
- tetanus drives repeated firing
- postsynaptic targets fire repeatedly due to the stimulation
- synapses are stronger than before
LTP
a stable and enduring increase in effectiveness of synapses
tetanus
brief increase of electrical stimulation that triggers thousands of axon potentials
mechanisms of synaptic plasticity
- low frequency stimulation causes presynaptic release of glutamate
- glutamate binds to glutamate receptors (AMPARs/NMDARs)
- AMPARs allow in Na+
- Mg2+ blocks NMDAR pore
- inside of postsynaptic neuron must be depolarized to electrostatically repel Mg2+
- AMPARs conduct Na+, causing Mg2+ to be repelled
- Na+ and Ca2+ enter through NMDARs
- high Ca2+ initiates protein kinases activation
- NMDARs are coincidence detectors
- pre and post synaptic neurons must overlap in activity - “coincidence”
- Ca2+ concentrations increase postsynaptically activating: PKC, PKA, CaMKII
- kinases activate CREB
- CREB enters nucleus to up-regulate plasticity related proteins, altering synaptic structure
- enhancement of postsynaptic response is due (in part) to endocytosis of AMPARs into the postsynaptic membrane, which can be due to CaMKII mediated phosphorylation
a mechanism for remote memory consolidation
- during sleep/rest hippocampus is reactivated so that episodic experiences are sent to cortex
- abstraction of rules/schemas are encoded by cortex and based on personal experiences encoded by hippocampus
- place cells’ replay and sychronization to cortex is a way to measure this phenomenon
place cells
- record place cells on linear but curved tack
- place cells in sequence based on position
- compare action potentials to theta rhythm (theta phase precession)
action potential
explain (lecture 18)
NMDAR is a coincident detector
- glutamate is released from neuron A axon terminals
- at the synapse, glutamate activates both AMPA and NMDA receptors
- NMDA can’t activate because Mg2+
- AMPARs can activate and allow in Na+
- Na+ causes depolarization, which then causes neuron B to become more positive
- positive charge causes Mg2+ to pop out of NMDA pore due to electrostatic repulsion
- once Mg2+ is out, glutamate can activate NMDARs fully
- NMDARs allow in both Na+ and Ca2+
- Ca2+ causes activation of protein kinases that result in transcription and translation of new genes/mRNA and proteins
synaptic plasticity underlies associative learning and memory
- learning occurs by changes in neuronal communication
- specifically, synapses change how they communicate with one another
- the process of changes in synaptic communication is synaptic plasticity
- not all synapses take part in learning, only some synapses will alter in response to learning
- if this change in synaptic communication is stable, then a new memory is formed
Hebb’s postulate
- when neuron A sends axon terminals to synapse onto neuron B and causes neuron B to fire action potentials repeatedly
- then there is production of new proteins by transcription, translation, and these new proteins go back to the synapses that were activated
- these new proteins go back to synapse and alter structure
- the change in structure makes it easy for neuron A to cause action potential in neuron B
- synaptic plasticity is the increased efficiency of neuronal communication
reverse replay
- occurs during periods of rest
- place cells fire in reverse order
- supports memory consolidation
sharp wave ripple complexes
- initiate place cell replay events
- fast 100-250 Hz EEG oscillation that occur during periods of rest
- such fast activity can result in long term potentiation of synapses, which may underlie learning and memory during sleep
- a form of unconscious learning
reverse replay of hippocampal place cells
- sharp wave ripples initiate the activation of place cells that were activated on a linear track
- this replay event can result in reverse or forward replay
- place cells encode where and when and theorized to generate a cognitive map
- cognitive map: the mental representation of space
LTP
- the enhancement of communication between neurons, that is, the efficacy
- LTP is a type of Hebbian plasticity
- LTP was first discovered at the perforant path-dentate gyrus synapse
- focus on CA3-CA1 synapse
- give test pulse with stimulating electrode along Schaffer Collaterals, the axons that synapse onto the CA1 dendrites
- record slope of EPSP
- after giving test pulse once a min every min for 30 min, give tetanus
- tetanus is 100Hz stimulation that occurs for 1 sec
- give test pulse after, which is same strength given before the tetanus, and measure slope of EPSP
- after tetanus the slope of field EPSP will be 50% greater
- plot abs value of EPSPs slopes before and after tetanus to observe “potentiation”
synaptic plasticity, amygdala, and fear conditioning
- synaptic plasticity underlies many aspects of learning and memory (like tone fear conditioning)
- one can break apart CS, US, CR, UR into distinct components of amygdala and it’s inputs
- sensory information, such as CS-tone and US-shock, will directly enter into the amygdala
- CS-tone will activate postsynaptic neuron, but postsynaptic response is minimal
- we can treat postsynaptic neuron as amygdala, as whole
- when amygdala neuron is only slightly activated there will be no overt fear response, which is what we would predict given CS-tone
- however, when US-shock is given, postsynaptic amygdala neuron will become highly activated, fire an action potential, and activate downstream targets, such as central grey, leading to UR-freezing
- when you pair CS-tone and US-shock, you are inducing synaptic plasticity at the CS-tone-amygdala-synapse
- now, after pairing, the tone will be able to activate the amygdala strongly, such that the amygdala neuron will activate downstream targets, such as the central gray, and result in freezing (CR)
physiology of systems consolidation
- remote LTM transfer from hippocampus to cortex
- this process occurs, in part, during sleep with reaction of place cells
- place cells are found in hippocampus CA1, CA3, DG subregions
- place cells activate/fire action potentials in specific regions of space
- when walking down path one place cell will increase in activity then decrease, as animal continues to move another place cell will begin to increase in activity then decrease as animal continues to move forward; this process occurs along entire pathway
- when animal takes a break and rests while on the track, but is still awake, the hippocampus will exhibit sharp wave ripples, which is an EEG signal between 100-250Hz
- this sharpe wave ripple causes reaction of the place cells that were active along track, this is called replay event
- replay is very fast, which means it can undergo synaptic plasticity
- synaptic plasticity supports hippocampal dependent memory consolidation of recent events
- a similar process occurs during SWS and REM sleep, which supports transfer of memories from hippocampus to cortex
- during REM reaction of place cells occur at 8-12x faster than when activated when animal is traveling across pathway, which supports synaptic plasticity
- during this time, this reaction the hippocampus is both consolidating recent LTM and transferring info to cortex
- over time, these recent memories transfer to cortex, that is, systems consolidation, where they become remote LTM
