Learning and memory

Question 1

Clive Wearing - Life without memory means no sense of existing across time

Answer 1

• Your memory is almost synonymous with your sense of self. (we see that in amnesia examples)
Example: Clive Wearing
• Viral encephalitis destroyd parts of brain
• Professional musician
• Developed amnesia from brain infection
• Unable to form lasting memories
(memory of ~30 sec)
- Waking up and feeling conscious for first time every day. And every moment of the day
- Crossing out entries in his diary all the time.

Question 2

Classical Conditioning and Pavlov’s explanation of learning

Answer 2

• Pioneered by Ivan Pavlov
• Pairing two stimuli changes the response to one of them
• Conditioned stimulus
• Unconditioned stimulus
• Unconditioned response
• Conditioned response

The experimenter
starts by presenting a conditioned stimulus (CS), which
initially elicits no response of note, and then presents the
unconditioned stimulus (UCS), which automatically elicits
the unconditioned response (UCR). After some pairings of
the CS and the UCS (perhaps just one or two, perhaps many),
the individual begins making a new, learned response to the
CS, called a conditioned response (CR).

Neural underpinning:
Likely, initially, unconditioned stimulus excites unconditioned response center. If you ring bell at same time, then only stimulates conditioned stimulus area initially. After pairing conditioned and unconditioned stimulus, conditioned stimulus area activity flows to unconditioned stimulus area, eliciting same response as unconditioned stimulus of unconditioned response area. = that classical conditioning reflects a strengthened connection between a CS center and a UCS center in the brain. That strengthened connection lets any excitation of the CS center flow to the UCS center, evoking a response just like the unconditioned response

We now know that this hypothesis does not fit all behavioral observations.

The primary difference
between classical and instrumental conditioning is that
in instrumental conditioning the individual’s response determines
the outcome (reinforcer or punishment), whereas in
classical conditioning the CS and UCS occur at certain times
regardless of the individual’s behavior. The behavior is useful,
however, in preparing for the UCS.

Question 3

Instrumental/operant Conditioning

Answer 3

• Individual’s response followed by reinforcer or punishment
• Reinforcers
• Events that increase the probability that the response will occur again
• Punishment
• Events that decrease the probability that the response will occur again

The primary difference
between classical and instrumental conditioning is that
in instrumental conditioning the individual’s response determines
the outcome (reinforcer or punishment), whereas in
classical conditioning the CS and UCS occur at certain times
regardless of the individual’s behavior. The behavior is useful,
however, in preparing for the UCS.

Question 4

Lashley’s Search for the Engram

Answer 4

• Lashley sought to understand where learning occurs in brain – involved lesioning cortex in many locations in rats, to search for “engram”, physical representation of what has been learned.
• Engram
• A physical representation of what had been learned
• Example: a connection between two brain areas
• Hypothesis: a knife cut between the two brain areas should abolish the newly learned response (from learning any new response)
• Hypothesis disproven (even if he made many lesions) – couldn’t find source of memory

Lashley also tested whether any portion of the cerebral cortex is more important than others for learning. Removed parts of the cortex. The lesions impaired performance, but the deficit depended more on the amount of brain damage than on its location  all cortical areas were about equally important for learning and memory.

Question 5

Lashley’s Principles

Answer 5

• Lashley’s experiments showed that learning and memory do not rely on a single cortical area
• Lashley’s principles about the nervous system
• Equipotentiality: all parts of the cortex contribute equally to complex functioning behaviors (e.g., learning) – and any part can substitute for another.
• Mass action: the cortex works as a whole, and more cortex is better
• Faulty Assumptions: only investigated cortex (we’ll see there are some work in cerebellum indicating we should look outside cortex), only investigated one type of learning (and assumed all had same physiological basis)

Question 6

Role of Cerebellum and Lateral interpositus nucleus (LIP) in learning/memory

Answer 6

• Richard F. Thompson and colleagues
• Suggested that the classical conditioning engram is located in the cerebellum, not the cortex
• Lateral interpositus nucleus (LIP) identified as central for learning (damage inhibits some kind of eye blink response)
• Responses increase as learning proceeds
• However, a change in a brain area does not necessarily mean that learning took place in that area
• PET scans on young adults led to the discovery that the cerebellum is critical for classical conditioning +People who have damage in the cerebellum show either no conditioned eyeblinks
• But only if the delay between onset of CS and UCS is short

Question 7

Types of Memory (short and long term, Hebb)

Answer 7

For much of the 20th century, most psychologists assumed that all memory was the same.
• Hebb (1949) differentiated between two types of memory:
• Short-term memory: memory of events that have just occurred
• Limited capacity
• Fade without rehearsal
• Short-term memories can be consolidated into long-term memory (strengthened, biological basis)
• Short term can be moved into LT
• Long-term memory: memory of events from times further back
• Can be stimulated with a cue
• They differ in terms of capacity; short term max 7 items, long term is vast – short term depends on rehearsal, you can reconstruct longterm memories that you haven’t thought about in years (but might not be completely accurate)
• Once you have forgotten something from short-term memory, it is lost. With long-term memory, a hint might help you reconstruct something you thought you had forgotten.

Question 8

Our Changing Views of Consolidation - not all memories transfer to long-term memory

Answer 8

Holding onto a memory for a long enough time does not automatically turn it into a permanent memory. (e.g. remembering where your car is parked for days doesn’t turn it into a long term memory)

• Consolidation time varies (e.g. for info on dangerous snake vs boring textbook)
• Emotionally significant memories form quickly = Flashbulb Memories
• Locus Coeruleus increases release of norepinephrine
• Emotion causes release of epinephrine & cortisol to activate amygdala and hippocampus—enhances consolidation of recent experiences
• = consolidation depends on more than the time necessary to synthesize some new proteins.
• Consolidated memories not permanent
• Reconsolidation – new experiences can modify the memory

“synaptic tag-and-capture” process: Your brain tags a weak new memory for later stabilization if a similar, more important event soon follows it

Question 9

Working Memory

Answer 9

• Proposed by Baddeley & Hitch as an alternative to short-term memory
• Emphasis on temporary storage of information to actively attend to it and work on it for a period of time
• Research points to the prefrontal cortex for the storage of this information
• Damage impairs performance on WM tasks
• Manner of impairment can be very precise (gives us lot of info on biological underpinnings of WM) – older individuals can have changes in WM, likely because of changes in PFC

A common test of working memory is the delayed response task

Question 10

Amnesia

Answer 10

• Amnesia is simply defined as memory loss
• Different kinds of brain damage result in different types of amnesia (damage to hippocampus often more severe amnesia)
• Two common types related to disorders:
• Korsakoff’s syndrome
• Alzheimer’s disease

Question 11

Korsakoff’s Syndrome

wernicke korsakoff syndrome

Answer 11

• Brain damage caused by prolonged thiamine (vitamin B1) deficiency (thiamine deficiency from insufficient nutrient consumption)
• Impedes brain’s ability to metabolize glucose
• Leads to a loss of or shrinkage of neurons in the brain (mammillary bodies in hypothalamus and dorsomedial nucleus of thalamus (book only says this one), projecting to frontal cortex)
• Often due to chronic alcoholism (not getting proper nutrition and vitamin b1, not because of alcohol, but intake leads one to not eat right diet – basically only drinks alcohol, not containing proper vitamins)
• Distinctive symptom: confabulation (taking guesses to fill in gaps in memory) – making up answer to a question.
• Also apathy, confusion, and memory loss
• Can experience both anterograde (unable to form new memories) and retrograde amnesia (can’t access old memories)

Question 12

Alzheimer’s Disease

Answer 12

• Dementia form occurring mostly in old people
• Associated with a gradually progressive loss of memory, confusion, depression, restlessness, hallucinations, delusions, sleeplessness, and loss of appetite., often occurring in old age, affecting almost 5 percent of people between ages 65 and 74 and almost half of people over 85
Their memory fluctuates from time to time, suggesting that part of their problem results from a loss of alertness or arousal
• Better procedural than declarative memory
• Better implicit than explicit memories (e.g. still able to do classical conditioning)
• Down’s syndrome usually get Alzheimer’s if they survive to middle age (gene on chromosome 21, which Down’s has 3 copies of, associated with early Alzheimer’s (before 60 years) but only accounts for 1 % of total cases)
• Affects 50 percent of people over 85 and 5 percent of people 65–74
• Early onset seems to be influenced by genes
• 99 percent of cases are late onset
• For the much more common late-onset condition, many genes increase or decrease the risk, but none has a large effect
• About half of all patients with late onset have no known relative with the disease
• No drug is currently effective
• New hope with Biogen’s aducanumab (might be hope for early stages)
• Often grey mater loss and atrophy, especially in temporal cortex.

Question 13

Alzheimer’s Disease and Proteins (biological causes)

Answer 13

• Alzheimer’s disease is associated with an accumulation and clumping of the following brain proteins:
• Amyloid beta protein
• Cause neuronal degeneration
• Creates plaques from damaged axons and dendrites
• The protein damages axons and dendrites, decreases synaptic input, and decreases plasticity
• Produces widespread atrophy of the cerebral cortex, hippocampus and other areas
many researchers are not convinced that amyloid-b by itself explains Alzheimer’s. Many old people have high levels of amyloid-b without Alzheimer’s disease, and some have Alzheimer’s disease without especially high levels of amyloid-b – no clinical trials of drugs that counteract amyloid-b have produced clear benefits for patients with Alzheimer’s

• An abnormal form of the tau protein (also accumulate abnormally)
• Creates tangles
• Part of the intracellular support system of neurons

High levels of amyloid-b cause more phosphate groups to attach to tau proteins. The altered tau cannot bind to its usual targets within axons, and so it starts spreading into the cell body and dendrites. The areas of cell damage in the brain correlate better with tau levels than with amyloid-b levels. The altered tau is principally responsible for tangles, structures formed from degeneration within neurons

• Though this combination of tau and beta plaques produce/implicated in AD – we don’t know if it is one, the other, something else, but we know it happens neurobiologically.
• Biogen’s aducanumab targets amyloid beta – developed from immune cells from older people without cognitive deficits, and used in AD trials. Many drugs targeting amyloid plaques don’t seem to work effectively
• Currently no drugs efficient – maybe because when AD is diagnosed, damage is too extensive for medication – one research goal is early diagnosis of AD.

Question 14

Infant Amnesia

Answer 14

• Early childhood amnesia—not a disorder like the previous two
• Universal experience—we don’t remember much from our first few years of life
• Children do form memories—the question is why they forget them
• Hypotheses:
• Learning language and complex reasoning abilities don’t develop until the child is older (but infant amnesia also demonstrated in animals without language)
• Changes in the hippocampus and growth of new neurons (hippocampus rapidly form new neurons, as new synapses and neurons replace old ones, they remove/weaken old ones (especially early in life) = might be why we have infant amnesia)
• In contrast to mice and humans, guinea pigs are relatively mature at birth, already walking around and eating solid food. They do not have rapid formation of new hippocampal neurons, and they do not tend to forget early memories the way rats and humans do.

Question 15

Hippocampus and the Striatum + patient HM and damage to hippocampus

Answer 15

two brain areas with contrasting functions in memory, the hippocampus and the striatum.
• Different areas of the hippocampus are active during memory formation and later recall
• Damage results in amnesia—and much of what we have learned about memory has been from patients with localized brain damage

• Person called H.M. is a famous case study in psychology
• Hippocampus from both hemispheres was removed to prevent epileptic seizures
• Afterwards, H.M. had great difficulty forming new long-term memories
• Short-term/working memory remained intact
• Suggested that the hippocampus is vital for the formation of new long-term memories
• H.M.’s short-term or working memory remained intact
• Was able to remember a number after 15 minutes without distraction
• When distracted, memory was gone in seconds
• Nothing new went into long term memory

Impaired Storage of Long-Term Memory
• H.M.’s memory impairments (could not learn new things – even new words in english language made after the surgery = were nonsense to him)
• Not being able to state the correct date or his current age
• Could read the same magazine or solve same puzzle repeatedly without losing interest
• Could recall only a few fragments of events in the recent past
• Did not recognize himself in a photo
• But did recognize himself in a mirror (largely comes from intact ability to have general knowledge, knowing what a mirror was, then knew it was him)

Semantic and Episodic Memory
Semantic memory
• Memories of factual information
• H.M. was able to form a few weak semantic memories
Episodic memory
• Memories of personal events
• H.M. could not describe any event since his surgery
• H.M. had severely impaired episodic memory
he could describe facts learned before operation, but could not remember personal events.
Also impaired his ability to describe the future

Question 16

Anterograde and Retrograde Amnesia

Answer 16

• Two major types of amnesia
• Anterograde amnesia: loss of ability to form new memory after the brain damage
• Retrograde amnesia: loss of memory of events prior to the occurrence of the brain damage
• H.M. showed both types of amnesia after the surgery (moderate amount of retrograde amnesia (could remember some events pre-removal – retrograde amnesia being most severe for the time leading up to the damage), and really severe anterograde amnesia)
H.M’s intellect and language abilities remained intact, and his personality remained the same except for emotional placidity

Question 17

Anterograde amnesia

Answer 17

Loss of ability to form new memory after the brain damage

Question 18

Retrograde Amnesia

Answer 18

loss of memory of events prior to the occurrence of the brain damage

Question 19

HM Working Memory

Answer 19

• H.M.’s short-term or working memory remained intact
• Was able to remember a number after 15 minutes without distraction
• When distracted, memory was gone in seconds
• Nothing new went into long term memory

Question 20

HM Impaired Storage of Long-Term Memory

Answer 20

• H.M.’s memory impairments (could not learn new things – even new words in english language made after the surgery = were nonsense to him)
• Not being able to state the correct date or his current age
• Could read the same magazine or solve same puzzle repeatedly without losing interest
• Could recall only a few fragments of events in the recent past
• Did not recognize himself in a photo
• But did recognize himself in a mirror (largely comes from intact ability to have general knowledge, knowing what a mirror was, then knew it was him)

Question 21

Semantic and Episodic Memory (and HM)

Answer 21

Semantic memory
• Memories of factual information
• H.M. was able to form a few weak semantic memories
Episodic memory
• Memories of personal events
• H.M. could not describe any event since his surgery
• H.M. had severely impaired episodic memory
he could describe facts learned before operation, but could not remember personal events.
Also impaired his ability to describe the future

Question 22

Implicit than Explicit Memory and Amnesia tendencies

Answer 22

Better Implicit than Explicit Memory = • Applies to nearly all patients with amnesia (can’t deliberately recall information)
• Memory loss impacts a person’s ability to imagine the future

Explicit memory
• Deliberate recall of information that one recognizes as a memory
• Also known as declarative memory – you can e.g. verbalize it.

Implicit memory
• The influence of experience on behavior even if one does not recognize that influence
• Another patient, not H.M., was tested with three nurses: one friendly, one neutral, one stern. He preferred the friendly nurse and avoided the stern nurse but couldn’t state why. (but he had some internal information that made him able to make a preferential choice)

Question 23

Procedural Memory and amnesia

Answer 23

• Procedural memory
• Development of motor skills and habits
• Special kind of implicit memory
• Examples of amnesia patients with intact procedural memory
• H.M. learned to read words written backward (as in a mirror)
• K.C. learned to use Dewey decimal system to sort books and is employed part-time at a library
• Can learn to play tetris, but don’t remember learning it.

Question 24

Normal/typical Pattern of Amnesia Patients

Answer 24

• Patient H.M. showed this pattern (as do many other amnesia patients):
• Normal working memory, unless distracted
• Severe anterograde amnesia for declarative memory
• Severe loss of episodic memories
• Better implicit than explicit memory
• Nearly intact procedural memory
• (could have some retrograde amnesia)

Question 25

The Hippocampus and Declarative Memory

Answer 25

• Research on hippocampus function suggests:
• Critical for declarative memory functioning (especially episodic memory)
• People with damage to it can often learn new skills, but not new facts

• Research with rats shows damage impairs abilities on two types of tasks:
• Delayed matching-to-sample tasks
• Subject sees an object and must later choose the object that matches
• Delayed nonmatching-to-sample tasks
• Subject sees an object and must later choose the object that is different from the sample
Used to test declarative memory

Here, monkey presented with sample object (key) – longer delay (so to not use WM) test phase, presented with original object – monkey has to learn that food is under object that differs (in non match to sample) or is the same (match to sample) – animal must remember where object was presented = declarative memory

If hippocampal lesions = impaired performance on the tasks.

Another hypothesis relates the hippocampus to memory for context - memory could not be
stored in a single location in the brain; it has to be spread over
many locations. Perhaps the hippocampus is a coordinator, a
director that brings together representations from various locations,
in the correct order. In short, it reconstructs the context.
 When people successfully retrieve an episodic memory, activity
in and around the hippocampus synchronizes with activity
in several parts of the cortex
 Recent episodic memories generally include much contextual
detail. Some older memories do also, but in most cases
the details fade and we remember only the gist of the event.
Memories with much contextual detail depend on the hippocampus,
but older, less detailed memories depend mainly on
the cerebral cortex with less contribution from the hippocampus

Question 26

The Hippocampus and Spatial Memory

Answer 26

Many hippocampal neurons are tuned to specific place and direction.
Taxi drivers: hippocampus activated when answering spatial questions (using PET scans). – cab drivers tend to have larger posterior hippocampus, likely because they have greater storage of spatial location info.
If hippocampus damaged – would impair one’s ability on spatial tasks.
• Navigation depends on your surroundings and your spatial memory – importance of hippocampus and surrounding areas.
• Damage to the hippocampus also impairs abilities on spatial tasks such as:
• Radial mazes: a subject must navigate a maze that has eight or more arms with a reinforcer at the end
• Morris water maze task: a rat must swim through murky water to find a rest platform just underneath the surface

Question 27

Cells Responsible for Spatial Memory

Answer 27

• Place cells: hippocampal neurons tuned to particular spatial locations, responding best when an animal is in a particular place and looking in a particular direction
• Time cells: some place cells also function as time cells that respond at a particular point in a sequence of time
• Place cells receive input from cells in the entorhinal cortex
• Recorded cells in the entorhinal cortex became active at locations separated from one another in a hexagonal grid. The cells are called grid cells. At a given level within the entorhinal cortex, different cells respond to different sets of locations, but always in a hexagon.

!!!!
Any episodic memory refers to events, occurring in a specific place, in a particular place in time – place cells represent many memories in many places/points in time. - A loss of place cells and time cells disrupts many types of memory formation.

Question 28

• Place cells:

Answer 28

hippocampal neurons tuned to particular spatial locations, responding best when an animal is in a particular place and looking in a particular direction.
• Place cells receive input from cells in the entorhinal cortex

Question 29

• Time cells:

Answer 29

some place cells also function as time cells that respond at a particular point in a sequence of time

Question 30

grid cells:

Answer 30

• Place cells receive input from cells in the entorhinal cortex
• Recorded cells in the entorhinal cortex became active at locations separated from one another in a hexagonal grid. The cells are called grid cells. At a given level within the entorhinal cortex, different cells respond to different sets of locations, but always in a hexagon

Question 31

The Striatum

Answer 31

to learn habits or learning what will or will not likely happen under a set of circumstances relies on part of the basal ganglia
• The striatum is the caudate nucleus + putamen

(compared to Episodic memory, dependent on the hippocampus, develops after a single experience.
• Many semantic memories also form after a single experience.
• Learning spatial location also develops quickly)

Question 32

Hippocampus vs. Striatum

Answer 32

division of labor between the striatum and other brain areas that include the hippocampus and cerebral cortex
• However, most tasks activate both systems
• Hippocampal learning at the beginning of a task, but once the task becomes “habitual” or “automatic,” more emphasis on striatum

Hippocampus:
Can learn in a single trial
Flexible responses
Sometimes connects information over a delay
Explicit
if damaged: Impaired declarative memory, especially
episodic memory

Striatum:
Learns gradually over many trials
Habits
Generally requires prompt feedback
Implicit
if damaged: Impaired learning of skills and habits

Question 33

Other Brain Areas (besides hippocampus and striatum) and Memory

Answer 33

• Most of the brain contributes to memory
• Amygdala associated with fear learning
• Parietal lobe associated with piecing information together – parietal lobe damage = problems associating different information pieces.
• Damage to the anterior temporal complex results in loss of semantic memory
• Semantic dementia – characterized by inability to match words/pictures with meaning – but can speak fluently and remember day to day events. Problems with permanent storage of info related to general world knowledge (might forget word hippopotamus, or lose knowledge about a hippopotamus) – unlike Alzheimer’s because memory of day to day events quite good.
• Prefrontal cortex involved in learned behavior and decision-making – damage disables ability to learn about rewards and punishments

Question 34

How does the Nervous System Store Information? The scientific journey and dead ends.

Answer 34

• Patterns of activity in the brain leave a path of physical changes
• Not every change is a specific memory
• Task of finding out how the brain stores memories is difficult
• Scientific progress is not smooth and straight, but more like exploring a maze with dead ends (many promising discoveries later refuted – e.g pennfield thinking each neuron stored info about specific stimuli, found not true. Or horridge thinking headless cockroaches could learn conditioning.) + several investigators proposed that each memory is coded as a specific molecule, probably RNA or protein. + attempt to transfer memories chemically from one individual to another. + an animal eating another learned some of its victims classical conditioning. + rats receiving extracts of other brains showed memory, but not replicable.

Question 35

Learning and the Hebbian Synapse

Answer 35

• Hebbian synapse (synaptic changes do correlate with memory)
• A synapse that increases in effectiveness because of simultaneous activity in the presynaptic and postsynaptic neurons
• “Cells that fire together, wire together”
• Such synapses may be critical for many kinds of associative learning

Consider how this process relates to classical conditioning.
Suppose axon A initially excites cell B slightly, and axon
C excites B more strongly. If A and C fire together, their combined
effect on B may produce an action potential. You might
think of axon A as the conditioned stimulus and axon C as
the unconditioned stimulus. Pairing activity in axons A and
C increases the future effect of A on B. A Hebbian synapse is
one that can increase its effectiveness as a result of simultaneous
activity in the presynaptic and postsynaptic neurons.

Question 36

A Slug’s Contribution to Learning

Answer 36

• Studies of how physiology relates to learning often focus on invertebrates and try to generalize to vertebrates
• The aplysia is a slug-like invertebrate that is often studied due to its large neurons (and fewer of them) (Vertebrate and invertebrate
nervous systems are organized differently, but the
chemistry of the neuron, the principles of the action potential, the neurotransmitters, and their receptors are the same)
• (gill withdrawal response behavior typically studied)
• This allows researchers to study basic processes such as:
• Habituation
• Sensitization

Question 37

Habituation

Answer 37

A decrease in response to a stimulus that is presented repeatedly and is accompanied by no change in other stimuli.
e.g. moved an apartment downtown – at first traffic and noise sounds really loud, but after a while, you stop noticing it = habituation.
Sea slug habituates – learn that waves are just there, stop “withdrawing” gills from them.
What we can demonstrate in sea slug is habituation to this kind of response – siphon, connected to sensory neuron, synapses to motor neuron, causing gill to withdraw – after touching slug many times, this behavior declines, because decreased transmission between sensory and motor neuron.
Calcium channel becomes less responsive to action potential = less NT released when AP generated.

Question 38

Sensitization

Answer 38

• Increase in response to a mild stimulus as a result to previous exposure to more intense stimuli (you become hypersensitive instead of accustomed to a stimulus (even familiar stimuli) = opposite of habituation) – explains likely some symptoms in PTSD (heightened response to stimuli)
• Changes at identified synapses include:
• Serotonin released from a facilitating neuron blocks potassium channels on PRESYNAPTIC terminal - potassium now flows more slowly out of the cell, the membrane repolarizes more slowly after an action potential. Therefore, the presynaptic neuron continues releasing its neurotransmitter for longer than usual.
• Prolonged release of transmitters from that neuron causes greater depolarization of post synaptic membrane, results in prolonged sensitization

Question 39

Long-Term Potentiation

Answer 39

• LTP reflects increased activity by the presynaptic neuron and increased responsiveness by the postsynaptic neuron

Repeated electrical stimulation of pathway enters hippocampus can increase EPSP size when recorded from hippocampal cells – increase in EPSP size can hold out for a long time.
• Long-term potentiation (LTP) occurs when one or more axons bombard a dendrite with stimulation
• Leaves the synapse “potentiated” (more responsive to new input of the same type) for a period of time and the neuron is more responsive

Properties of Long-Term Potentiation
• Specificity: only synapses onto a cell that have been highly active become strengthened
• Cooperativity: simultaneous stimulation by two or more axons produces LTP much more strongly than does repeated stimulation by a single axon
• Associativity: pairing a weak input with a strong input enhances later responses to a weak input (matches Hebbian synapse)

Long-Term Potentiation: how it occurs:
Simultaneous stimulation from axon 1 and 2 –> generate simultaneous stimulation, depolarizing post synaptic neuron with stronger
Dots in right diagram shows EPSPs –> increase in amplitude tells us LTP has occurred.

Simultaneous strong + weak makes stronger synapse for both axons to post synaptic dendrites

Question 40

• Specificity of LTP:

Answer 40

only synapses onto a cell that have been highly active become strengthened

Question 41

• Cooperativity of LTP:

Answer 41

simultaneous stimulation by two or more axons produces LTP much more strongly than does repeated stimulation by a single axon

Question 42

• Associativity of LTP:

Answer 42

pairing a weak input with a strong input enhances later responses to a weak input (matches Hebbian synapse)

Question 43

Long-Term Depression (LTD)

Answer 43

Instead of high frequency stimulation, low frequency stimulation  LTD
• A prolonged decrease in response at a synapse that occurs when axons have been less active than others
• Compensatory process: as one synapse strengthens, another weakens
• LTD might be mechanism to clear out old memories (and LTP might be mechanism for creating new ones)

Question 44

Biochemical Mechanisms of LTP (describe the chemical process of LTP)

Answer 44

• Studied most in the hippocampus
• LTP depends on changes at glutamate synapses
• Also GABA synapses, to a lesser extent
• Two types of glutamate receptors
• AMPA receptors
• NMDA receptors
• These are both usually excited by glutamate, but can also respond to drugs
• Both are ionotropic receptors. That is, when they are stimulated, they open a channel to let ions enter the postsynaptic cell.

What happens before LTP:
presynaptic neuron releases glutamate into synaptic cleft, glutamate can attach to both of the receptors – on ampa receptor, it is ionotrophic, sodium flows in. – on nmda, glutamate binds, fail to open channel because magnesium blocks this.

WHAT THEN HAPPENS:
• To activate nmda receptor and remove magnesium:
• Repeated glutamate excitation of AMPA receptors depolarizes the membrane of postsynaptic cell.
• The depolarization displaces magnesium molecules that had been blocking NMDA receptors
• Glutamate is then able to excite the NMDA receptors, opening a channel for calcium ions to enter the neuron (and sodium)
• Entry of calcium is key for LTP
• Entry of calcium through the NMDA channel triggers further changes
• (activation of genes that produce the protein caMKII) Activation of a protein (caMKII) sets a series of events in motion (e.g. dendrite able to build more AMPA receptors and move them into better positions + dendrites may make more branches to connect with same axons + AMPA receptors may become more responsive)
• More AMPA receptors are built and dendritic branching is increased
• These changes potentiate the dendrite’s future responsiveness to incoming glutamate

caMKII necessary for LTP: Because activated CaMKII remains at the stimulated synapse and does not diffuse elsewhere, it is responsible for the specificity aspect of LTP—the fact that only the highly activated synapses become strengthened

Extra:

CREB goes to the nucleus of the cell and regulates the expression of several
genes. In some cases, the altered gene expression lasts
for months or years, long enough to account for long-term
memory. It is an example of an epigenetic change, depending on histone modifications

The effects of CaMKII and CREB are magnified by
BDNF—brain-derived neurotrophic factor, a neurotrophin
similar to nerve growth factor. Persisting activity at synapses
leads to action potentials that start in axons but backpropagate
into the dendrites, which then release BDNF. The
formation and maintenance of LTP depends on all these
chemicals—CaMKII, CREB, and BDNF (and others) – those with with of these chemicals will have most LTP.

In some cases, LTP depends on mechanisms that increase
the responsiveness of AMPA receptors (Lauterborn et al.,
2016; Lisman et al., 2012). In many other cases it depends on
building new branches of dendrites and synapses with either
AMPA or NMDA receptors

Once LTP has been established, it no longer depends on NMDA synapses.

Question 45

Presynaptic Changes in LTP

Answer 45

• LTP also causes presynaptic changes
• Changes in the presynaptic neuron can also cause LTP
• Extensive stimulation of a postsynaptic cell causes the release of a retrograde transmitter (Often nitric oxide NO) that travels back to the presynaptic cell to cause the following changes:
• Decrease in action potential threshold
• Increase neurotransmitter release
• Expansion of the axons (axonal membrane)
• Transmitter release from additional sites

When both presynaptic and postsynaptic changes contribute to LTP, the result is greater precision and stability of learning

Question 46

Can We Improve Memory?

Answer 46

Understanding the mechanisms (chemicals) of changes that impact LTP may lead to drugs that improve memory
• Caffeine, Ritalin, and Modafinil enhance learning by increasing arousal
• Some herbs have doubtful effects
• Ginkgo biloba (mostly for alzheimer’s, over long time)
• Bacopa monnieri (removes b-amyloids, so theoretically it seems a reasonable candidate for improving memory, but after long time)
• Altering gene expression in mice
• Slight benefits to certain types of memory
• Improvements come with a cost: generally impair a different type of memory
• Example: NMDA receptors—faster learning but chronic pain
• In humans: electrical stimulation to parts of the parietal or prefrontal cortex could improve certain types of memory, but always at the cost of impairing a different type of memory
• tDCS: possibly helps people improve attention and memory (helps one function, impairs another)
• Behavioral methods best way to improve memory
• Study, rehearse, test yourself, get good sleep, and reduce stress!

Question 47

Intelligence

Answer 47

• Intelligence includes learning, memory, reasoning, and problem solving.
• Is a difficult concept to define
• Charles Spearman’s (1904) report (one of first attempts/discovery in psychology)
• All measures of cognitive performance correlate positively with one another.
• Idea: Factor of general intelligence = g
• General intelligence similar to general athletic ability
• BUT! Some people are good at one skill and others different skills

Question 48

Brain Size and Intelligence

Answer 48

Brain Size and Intelligence
• Bigger brain does not mean “smarter”
• All mammalian brains have the same organization, but they differ greatly in size.
• Within a family (e.g., rodents), larger species, which have proportionately larger brains, learn faster and retain their learning better than smaller species.
• This is not true if you compare species (e.g., human vs. whale)

Question 49

Body to Brain Ratio

Answer 49

• The species humans regard as most intelligent—ourselves—have larger brains in proportion to body size than do species we consider less impressive, such as frogs.
• Body to Brain Ratio
• Doesn’t make sense for certain species, for example, Chihuahuas, squirrel monkeys, and marmosets
• Human obesity is reducing our ratio!

Question 50

Total Number of Neurons

Answer 50

• Humans win!
• Total number of neurons may be a reasonable correlate of intelligence
• Whales and elephants have larger brains than humans, their neurons are larger and more spread out.
• Marmosets have a greater brain-to-body ratio than humans, but their bodies are smaller, and therefore their brains and neuron number are smaller.

Question 51

Human Data - brain size and intelligence

Answer 51

Human Data
• Moderate correlation between brain size and IQ
• Intelligence correlates with surface area of the cerebral cortex (dense with cell bodies) in the frontal and parietal lobes as well as with the caudate nucleus
• Intelligence also correlates with white matter
• = BOTH neurons and the connections among neurons are important
Limitations with the Human Data
• Men have larger brains but equal IQs
• Overall, males and females have equal intelligence
• women do somewhat better than men on certain aspects of language, including fluency, and on average men do somewhat better than women on certain spatial skills
• Hypotheses for why equal IQ, but not equal brains:
• Women have more and deeper sulci on the cortex  surface area almost equal to men
• Male and female brains organized differently possibly as an evolutionary mechanism to keep intelligence the same despite the relative size
• The correlation is not high enough to justify using brain measurements to make any decisions about an individual

Question 52

Genetics and Intelligence

Answer 52

• Genetics play a role
• Monozygotic twins resemble more alike than dizygotic twins on tests of overall intelligence, specific cognitive abilities, and brain volume
• Resemble each other even when reared in separate homes (gives some idea genetics must play a role)
• Heritability increases as people grow older
• Adopted children start more similar to adoptive parents but gradually become more like biological parents (might be because they with their genetic predisposition gravitate specific environments, e.g. academically challenging surroundings)
• Heritability of intellectual performance is lower for people raised in impoverished conditions and who attended lower-quality schools
•  so genetic predisposition to e.g. be more intelligent is not “expressed” if opportunity to use it isn’t there
• Overall: Significant heritability, contributions from many genes, but no common gene with a major effect

Question 53

Brain Evolution - how do we get such “better brains” through evolution?

Answer 53

Except for the specializations related to language, human
brains are organized the same way as those of other mammals,
especially other primates. We have the same types of
neurons, the same neurotransmitters, the same types of synapses,
approximately the same ratio of neurons to glia cells,
the same ratio of cortex to cerebellum, and so forth (Harris
& Shepherd, 2015; Herculano-Houzel, 2012). Nearly all the
differences between humans and other species are quantitative.
Just a few genetic differences between humans and
other primates are enough to cause more rapid and more
prolonged production of neurons during embryological development,
leading to a larger cerebral cortex and a larger
number of neurons

The brain is a metabolically expensive organ.

For our remote ancestors to evolve such large brains, they
needed to get a great deal of nutrition, but they also needed to
reduce the energy spent on other functions. Our upright walking
is efficient and saves energy – learning to cook food saves energy in digestion.
+ We have more of the protein that transports glucose
into the brain, and less of the protein that transports it into the muscles.

Our remote ancestors also decreased the energy required
for reproduction (fewer children, but better chances for survival)

cooperation reduced energy expenditure on caring for infans, hunting, etc.