21, 22: Learning and Memory

Declarative memory is said to deal with _______ questions.

"what"

LTM

An enduring memory that last from days to years and has infinite capacity

Classical conditioning

An initially neutral stimulus comes to predict an event. The famous experiment involves a dog learning to salivate when presented with a tone that came to predict the presentation of food. The unconditioned stimulus is the food, which evokes the unconditioned response of salivating. The tone is the conditioned stimulus and the learned response to the conditioned stimulus, salivation, is the conditioned response.

Priming

A change in the way you process a stimulus, usually a word or a picture, because you've seen it or something similar previously. It does not require declarative memory (i.e. HM can show priming). Priming is not impaired by basal ganglia damage. There are two types: perceptual (visual form of words) and conceptual (based on word meaning). It can occur in all types of sensory modalities

Short- term Habituation

A decrease in response to a stimulus as it is repeated due to less transmitter release

Hippocampus

A medial temporal lobe structure that is important for learning and memory.

Cognitive map

A mental representation of the relative spatial organization of objects and information. This is formed when rats learn a maze. They don't simply learn a series of turns

Patient N.A.

A miniature sword entered his nostril and injured his brain. He has profound anterograde amnesia. He has damage to the dorsomedial thalamus and mammillary bodies. He can gain nondeclarative memories.

Memory trace

A persistent chance in the brain that reflects the storage of memory. It doesn't deteriorate from disuse and the passage of time; instead, memories suffer interference from events before or after their formation

What is likely the function of the mammillary bodies in learning & memory?

A processing system connecting the hippocampus and nearby cortex to the thalamus, and from there, to other cortical sites

Amensia

A severe impairment of memory, usually as a result of accident or disease

Dentate gyrus

A strip of gray matter in the hippocampal formation

Hebbian synapse

A synapse that is strengthened when it successfully drives the postsynaptic cell. "Cells that fire together wire together". When a group of presyn neurons fire at the same time, they "gang up" on the postsyn cell, depolarizing it enough that the NMDA receptors are activated and connections are strengthened. The neurons that fired out-of-synchrony are pruned and the in-synchrony synapses create more connections

Delayed non-matching-to-sample task

A test of object recognition memory that requires monkeys to declare what they remember. Monkeys identify which of two objects was NOT seen previously. Monkeys with extensive damage to medial temporal, like HM, are severely impaired

Emotional affect on memory

Adrenal stress hormones that're released during an emotional event will enhance that memory, so emotional memories are actually more easily remembered. This enhancement disappears with beta-blockers which block the effect of epinephrine. Lesions to the amygdala incur a similar effect. However, injections of epinephrine into the amygdala will enhance memory formation.

Operant or instrumental conditioning

An associated is formed between the animal's behavior and the consequences of that behavior. For example, the Skinner box where pressing bar is rewarded with food.

Studies of brain-lesioned individuals, as well as imaging studies, indicate that the learning of sensorimotor skills, perceptual skills, and cognitive skills are all affected by lesions specific to the

Basal ganglia

What brain areas are involved in sensorimotor skill learning?

Basal ganglia, cerebellum, and motor cortex

Why are different brain regions activated when you're reading a story about yourself vs. someone else?

Because the story about yourself is episodic while the story about someone else is semantic. These memories are stored in separate locations. Episodic memory activates right frontal and temporal lobe regions

The most convincing evidence for a link between LTP and learning comes from

Behavioral LTP

NMDA receptors are gated by

Both A. the ligand glutamate. B. partial depolarization of the membrane.

What fact suggests STMs are more vulnerable to trauma than LTMs?

Brain trauma often causes retrograde amnesia without affecting older memories. Freshly consolidated LTMs may be lost as well, but older memories are more "secure"

The increase of cortical thickness with enriched experience is probably mainly due to the increased

Branching of dendrites

What brain structures store declarative memories?

Cerebral cortex

What showed the sea slug, Aplysia, learns to habituate?

Changes in the synapse between the sensory cell that detects a squirt of water and the motorneuron that retracts the gill occur as less and less transmitter is released at the synapse and the gill withdrawal response to the stimulation fades.

Hippocampal formation

Consists of the hippocampus and the dentate gyrus

What causes the denial and confabulation in Korsakoff's syndrome?

Damage to frontal cortex

Which of the following kinds of brain damage has not been associated with an inability to form declarative memories?

Damage to the anterior cerebral cortex

Episodic memory

Detailed autobiographical declarative memory. The ability to recall a specific episode in your life or relate an event to a particular time and place.

Subtypes of declarative and non-declarative memory and associated brain regions

Different forms of memory rely on different brain mechanisms. But, the same brain structure can be a part of the circuitry for several different forms of learning

The adage "cells that fire together, wire together" refers to a hypothesis proposed by

Donald Hebb.

3 processes of a memory system

Encoding Consolidation Retrieval

Retrieval

From stored info of LTM for use

Semantic memory

Generalized declarative memory. The ability to recall the meaning of a word without knowing where or when you learned the word.

AMPA receptor

Glutamate receptor that also binds that glutamate agonist AMPA

NMDA receptor

Glutamate receptor that also binds the glutamate agonist NMDA and is both ligand-gated and voltage-sensitive

Basal ganglia

Group of forebrain nuclei, including the caudate nucleus, globus pallidus, and putamen found deep within the cerebral hemispheres. They are crucial for skill learning

Long-term habituation

Habituation occurring over a series of days. Each successive day, habituation occurs quicker and quicker. This occurs by the reduction of the number of synapses between the sensory cell and motorneuron.

Patient H.M.

Had severe seizures, and underwent surgery to remove the anterior temporal lobe (including the amygdala and most of the hippocampus) on both sides of the brain. Cerebellum shrinked overtime due to loss of hippocampal inputs. The seizures stopped, but he had severe anterograde amnesia. He could recall immediately a list of 7 numbers, but could not recall a list of words when tested the next day, or even that there was a list. It was the first indication that short-term and long-term memory were separate

Adult mice living in enriched conditions produce new neurons in the

Hippocampus

What brain area is required for consolidation, but not encoding or retrieval?

Hippocampus

How do we know HM could still form nondeclarative memories?

His performance on mirror-tracing tasks improved, despite him not even remembering doing the mirror-tracing task the days before.

3 stages of memory

Iconic, STM or working memory, and LTM

What experiment shows the basal ganglia involved in response recognition memory?

In the 1st part of the trial, the rat is placed in a compartment of one side (2 or 5) and it finds food if it enters the compartment either to its right or left. When placed on the opposite side, it only finds food if it turn to the same side of its body as before. It therefore must remember if it made a right or left turn.

STM or working memory

In the absence of rehearsal, these last about 30 seconds. With rehearsal, they may last a few minutes. It is where we hold information while we're working with it to solve a problem. It can hold about 7 things.

What experiment showed the hippocampus involved in spatial location memory?

In the study phase of each trial, the rat can choose any of 8 arms in a radial maze. In the test phase, doors block al but 2 arms: one arm from the study phase and one not. The rat only receives a food reward if it enters the arm from the study phase. With hippocampal lesions, rats only guess correctly 50% of the time.

What experiment shows the cortex involvement in object recognition memory?

In the study phase, rat obtains food by displacing an object. In the test phase, the rat chooses between two object and only obtains food if it chooses the object that it has not seen before. This is also called non-matching-to-sample.

Patient K.C.

Incurred brain damage in a motor cycle accident. Damage occured in left frontoparietal and right parieto-occipital cerebral cortex (causing loss of episodic memory), as well as hippocampal and nearby cortical shrinkage (causing anterograde declarative amnesia). He can even gain more semantic memory, but not episodic memory. Showed these two types of memory are processed and stored in different locations

Nonassociative learning

Learning in which stimulus alters the strength or probability of a response according to the strength/timing of the stimulus. This includes habituation and sensitization.

Associative learning

Learning that involves relations between 2 events, i.e. a stimulus and a response. An example is classical conditioning

Dorsomedial thalamus

Limbic system structure connected to the hippocampus

Mechanism of LTD

Long-term depression occurs in the same cells. CA3 cells project to CA1 cells through Schaffer collaterals. Instead of high-freq stimulation, we give low-freq stimulation of about 1 Hz. You don't see LTP, you see LTD. This means the response of the post-syn cell is lower EPSPs than before. Mechanism is based on a decrease in influx of Ca. With low levels of Ca, instead of activating calcium-dependent phosphorylation pathways, pathways that dephosphorylate are activated. AMPA receptors are internalized and less receptors are synthesized. Basically, the opposite of LTP occurs. LTP is not necessarily remembering, and LTD is not necessarily forgetting. This is a way of changing synaptic relationships. The relationships between cells depend on whether they're excitatory or inhibitory. If you decrease the activity in an inhibitory pathway, then you get excitation, which is remembering! It's all about context of the cell.

LTP

Long-term potentiation; a stable and enduring increase in the effectiveness of synapses following repeated strong stimulation. Occurs in conscious, anesthetized animals and in tissue slices through at least 3 different pathways. It has been shown to be a kind of synaptic plasticity that underlies certain forms of learning and memory

Retrograde amnesia

Loss of memories that formed prior to an event. Often occurs for memories of the few hours or days prior to the accident

When inactive, NMDA channels are blocked by molecules of

Mg2+

Why does natural selection favor larger hippocampus in bird species?

Most bird species hide food in various locations. Larger hippocampus means more place cells to enhance spatial learning

Glutamate

Most common excitatory neurotransmitter

Mechanism behind most-studied for of LTP

NMDA channel is normally blocked by Mg2+ and only AMPA is functioning to allow Na+ in response to glutamate at CA1 synapses, but Mg2+ is kicked off with repeated AMPA receptor activation, allowing Ca2+ in as well. Ca2+ triggers second messenger systems increasing the number of AMPA receptors in the membrane and increases their sensitivity/conduction of ions, causing LTP. More AMPA receptors mean a stronger response to transmitter. Retrograde transmission occurs with NO often as well

What somatic evidence is there fore LTP as a mechanism in memory formation?

NMDA receptor blockade interferes with success on memory tests. Lack of functional NMDA receptors via knock-out causes impaired LTP in hippocampus and declarative memory. Overexpression of NMDA in hippocampus results in enhance LTP

Place cells

Neurons in the hippocampus that selectively fire when the animal is in a particular location. Are involved in spatial learning

What types of structural changes of synapses occur in learning?

New synapses form or old synapes die as a result of use (c), or reorganization of connections (d)

Retrograde transmitter

Often a diffusable gas released by the post-synaptic cell that acts on the presynaptic cell causing more glutamate to be released in LTP, thereby strengthening the synapse. So now the post-syn cell is causing the release of more glutamate from the pre-syn cell through retrograde transmission.

Repeated reconsolidation

One of the best ways to improve learning

Mammillary bodies

Pair of limbic system structures connected to the hippocampus

What experiment concluded there is no upper bound to memory capacity?

People viewed long sequences of color photos of various scenes. When showed these several days later, and asked to identify the images seen previously, subjects performed to a high degree of accuracy for up to 10,000 stimuli

What does an fMRI of priming show?

Perceptual priming shows reduced activity in occipitotemporal cortex, while conceptual priming shows reduced activation of the left frontal cortex

What happens to place cells when animal is in a new environment?

Place cells remap the new location

What types of physiological changes of synapses occur in learning?

Pre- and post- synaptic, such as amount of neurotransmitter (a), number or sensitivity of receptors (a), or changes in pre-synaptic inputs (b)

What will blockage of NMDA receptors cause?

Prevents new LTP in that region

Skill learning

Process of learning how to perform a challenging task simply by repeating it over and over, e.g. mirror tracing

What study showed environment is linked to changes in the brain?

Rats were set in one of three conditions: standard, impoverish, or enriched. EC had a heavier, thicker cortex, showed enhanced cholinergic activity, had more dendritic branches and spine, larger cortical synapses consistent with LTM storage, more neurons in the hippocampus, and enhanced recovery from brain damage.

Encoding

Raw information is moved from sensory channels into STM

U-shaped serial position curve

Results from learning lists of words or numbers and usually displays primacy and recency effects. If the delay prior to recall is extended, the recency effect disappears. Primacy effect only occurs if there is some delay in responding, suggesting time is needed to get items into LTM.

Imaging studies of episodic memory have revealed that listening to autobiographical information, relative to other types of information, produces increased activation of the _______ and _______.

Right frontal lobe; right temporal lobe

Consolidation

STM into LTM

3 kinds of skill learning

Sensorimotor (mirror tracing), perceptual (learning to read mirror-reversed text), and cognitive (planning and problem-solving)

Which of the following statements about plastic changes at the level of the synapse is false?

Synapses of less active neural pathways start competing for neurotransmitter by engulfing neighboring synapses.

What do the primacy vs recency effect illustrate?

The STM and LTM rely on different processes to store information.

Neuroplasticity

The ability of the nervous system to change in response to experience or the environment.

What brain region is associated with classical conditioning?

The cerebellum. Classical conditioning can only occur if the cerebellum is intact, and if only half of it is intact, then conditioning occurs only on the side of the body where the cerebellum is intact

What brain area is crucial for spatial learning?

The hippocampus

Which brain structures are important for declarative memory?

The hippocampus and surrounding cortex, especially entorhinal, perirhinal, and parahippocampal. You need at least one intact hippocampus to make new declarative memories. Lesions to just hippocampus won't completely impair declarative memory, lesions of surrounding cortex are needed as well

What brain structures form declarative memories?

The hippocampus, mammillary bodies, and dorsomedial thalamus

Anterograde amnesia

The inability to form new memories after an event

Iconic memory

The most brief type of memory. Stores the sensory impressions of a scene. Thought to be residual activity in sensory neurons--so-called sensory buffers

What do most theories of learning focus on?

The plasticity of the structure and function of synapses

Reconsolidation

The return of a memory trace to stable long-term storage after it has been temporarily made changeable during the process of recall. When returned to LTM, memories may be distorted or altered

Recency effect

The superior performance seen in a memory task for items at the end of a list. It is usually attributed to STM

Primacy effect

The superior performance seen in a memory task for items at the start of a list. It is usually attributed to LTM

Branch order

Their numbering is indicative of how far they've branched from the cell body. As they continue to branch, one number is added. Highly branched dendrites therefore have higher numbers. This method is able to quantify the complexity of the cells. The highest number on the branch is the "branch order."

Why did experimental bilateral hippocampal lesions in laboratory animals not produce widespread memory deficits?

There are different kinds of memories, and lesions of hippocampus like with HM affect declarative memory.

Why is Aplasia a good model for memory?

They have relatively few neurons that are arranged identically in different individuals

Korsakoff's syndrome

Thiamine deficiency that leads to brain damage in the limbic system causing a loss of a sense of familiarity with some items and confabulating, or filling a gap in memory with lies that they believe are true. These people deny there is something wrong. Often associated with alcoholism. Damage cannot be reversed but can be prevented with thiamine supplements.

Nondeclarative memory

Things you know that you can show by doing. Tests of this include performing specific tasks. It answers "how" questions.

Declarative memory

Things you know that you can tell others. Tests of declarative memory take the form of requests for specific information. It answers "what" questions.

What correlational evidence is there fore LTP as a mechanism in memory formation?

Time course of LTP and time course of memory formation are similar-- induced within seconds, lasts days to weeks, and even LTP resembles similar vulnerability as STM to accidents

What behavioral evidence is there fore LTP as a mechanism in memory formation?

Training an animal in a memory task induces LTP somewhere in the brain, especially with fear conditioning.

Describe the circuit involved in classical conditioning using the eye-blink response.

Trigeminal pathway carries information about the corneal stimulation to the cranial otor nuclei and also sends axons to the brainstem. The brainstem sends climbing fiber to cerebellar neurons, which also receive auditory information from the auditory nuclei. So, the US and CS information converge in the cerebellum. After conditioning, the ton has an enhanced effect on cerebellar neurons, triggering the eye blink in the absence of the air puff.

CA1 and CA3

Two areas of the hippocampus. Pyramidal neurons in CA3 send long axons called schaffer collaterals to CA1.

What are the drawbacks of exceptional memories?

Usually unimportant memories are pruned out, but continual perfect recall can become uncontrollable, exhausting, and distracting

What experiment showed LTP occurs on a synapse-by-synapse basis?

We are looking at the effect of stimuli given to Schaffer collaterals and how this changes CA1 neurons. We give a stimulus at pathway 1, and look at the size of EPSPs afterwards. . We see an EPSP of particular size on pathway 1 before tetanus. There is an increased size of EPSP after tetanus (b). If you are looking at the effect in pathway 2, there is none based on stimuli in pathway 1 (b). In pathway 2, a stimulus gives an EPSP, but there is no period of tetanus in pathway 2. So, there is the exact same EPSP before and after tetanus of pathway 1 in pathway 2. This means LTP occurs on a synapse-by-synapse basis. You can see in pathway 2 that the size of EPSP stayed the same over 60 minutes (c) and 360 days, while the size of EPSPs in pathway 1 is double or triple over 60 minutes (c) and even still occurs a year later (d).

What experiment showed evidence of LTP?

When a tetanus is applied to presyn neurons, causing them to produce more APs, the postsyn neurons have a greater response. In other words, the synapses appear to have become stronger or more effective

The main cause of Korsakoff's syndrome is

a lack of thiamine

Evidence indicates that working memory for one's own motor responses is related especially to the functioning of the

basal ganglia.

Which memory store holds the largest number of items?

long-term memory

Design studies in each category that would prove LTP involvement in memory in the cortex.

o Correlational • Amount of AMPA receptors in rodent primary motor cortex and correlating intelligence in different strains of mice. Do rodent species that are faster maze learners have more AMPA receptors in the primary motor cortex which may suggest LTP contributing to improved memory? • May need a more specific area than M1. o Somatic intervention • Administer a drug to the cortex that would inhibit the function of Camodulin Kinase II or PKC, and then have the animal take memory tests. This would disrupt the LTP pathway, while still allowing glutamate its normal important functions in the brain. If there is a significant drop in memory ability, then LTP is likely involved in cortical memory. • Make a knockout mouse without the NMDA receptor in a brain area and see if the mice couldn't learn things involved in that brain area. • Inject a drug that would increase the amount of NO gas in the cortical area of a rodent and observe behavior o Behavioral intervention • BAD EXAMPLE: Have business students and neuro students take neuro final and track LTP using EEG while they're taking the final. EEG cannot track LTP because LTP occurs at individual cell and individual synapses. This implies all your neuro knowledge is stored in one spot in the brain. This is too global—such as neuro vs. business knowledge. We need more specific pre- and post- synaptic regions. • Teach a person a new motor skill, such as how to draw a picture with their left hand. At various points throughout the training process, you would measure the EPSPs at the post-syn cell in M1 to see if LTP occurs as training proceeds and after training has finished. This needs further focus. Drawing a picture with your hand involves too many brain areas. • Observe changes in electrical responses at the synaptic level to faces when initially presented and then in subsequent presentations. This takes advantage of the FFA, fusiform face area. Measuring electrical response of pre and post-syn cells in initial presentation of a series of faces. After a short time, present another series of faces, some being ones from the previous set and some being novel.

In LTP formation, nitric oxide may serve as

retrograde transmitter

The eightarm radial maze is used primarily for tests of

spatial learning and memory