pbsi 235 learning and memory

what is learning?

is the process by which new information is acquired for storage.

what are the properties of learning?

• •It is initiated by experience

• It selects the information that enters into memory

  • Learning filters experience, separating out relevant stimuli for retention

Ebbinghaus tested his own retention of a series of nonsense syllables, and documented the ‘forgetting curve’:

He showed that most forgetting occurs right away and then continues at a slower rate over a longer period

In Principles of Psychology (1890), William James proposed a multi-stage process of memory, in which multiple, independent ‘traces’ are initiated simultaneously and last for a different period of time:

In Principles of Psychology (1890), William James proposed a multi-stage process of memory, in which

multiple, independent ‘traces’ are initiated simultaneously and last for a different period of time

Long term memory requires

consolidation

what is consolidation? 

the process by which a long-term memory stabilizes for storage over an extended period of time

consolidation beings with _________ (LE) and occurs in parallel with ______

original learning experience and short-term memory

Consolidation is why long-term memory endures in an

inactive state (while short term memory is always vulnerable to disruption)

, human memory can be divided into two broad categories: 

• declarative

• non-declarative

what is declarative memory?

• explicit – you can describe the contents of memory using language

  • includes learned motor skills (i.e. so-called muscle memory, known as procedural memory)

what is non-declarative memory?

• implicit – it is difficult to describe the contents using language

  • your conscious recollection of previous experience (i.e. what happened to you where and when, known as episodic memory) 

When accessing declarative memory, you are _____ of the fact that you are engaged in a process of remembering. Accessing implicit memory seems more ____, to the extent that you don’t feel as if you’re using memory at all

aware and automatic

what is amnesia

is a strong memory impairment

what is retrograde amnesia?

is a loss of previously acquired memories

what is anterograde amnesia?

is an inability to form new memories

The early stages of dementia are often categorized by anterograde amnesia, followed by retrograde amnesia that roughly follows Ribot’s Law:

• newer memories are less resistant to disruption than older ones.

  • So memories just prior to the onset of dementia are lost before childhood memories

Patient HM (Henry Molaison)

• Experienced debilitating seizures starting at 16, had surgery to remove epileptic foci (point of origin for his seizures) at 27

• Surgeon removed his medial temporal lobe, including the hippocampus

  • His epilepsy was cured, but he was left with profound memory impairments

Brenda Milner performed the neuropsychological assessments of HM

She found:

• Shallow retrograde amnesia with intact long-term episodic memory

  • HM’s memory of childhood and young adulthood remained in place

• Intact short-term episodic memory

  • HM could remember what happened to him a few moments ago

she found what pt2: 

• Profound anterograde amnesia: following surgery he couldn’t form new long-term episodic memories

  • She worked with him for years, and everyday she met him she had to introduce herself

HM’s problems are explained by a consolidation deficit.

• The surgery disrupted memories still in the process of consolidation, hence the shallow retrograde amnesia

• The surgery prevented the consolidation of new long-term memories

  • hence the inability to form anything other than a short-term trace

What is the role of the hippocampus in episodic memory according to the system consolidation model?

• The role of hippocampus in episodic memory is temporary.

  • Once a memory has been consolidated, hippocampus has no role.

• Permanent memory storage is distributed across cortex.

  • Hippocampus guides this process and drops out once it is complete.

How does the hippocampus help consolidate memory in the system consolidation model?

• Hippocampus is thought to do this by recreating patterns of brain activity that occurred during experience, called replay.

• Activation of hippocampal neurons during replay is thought to drive activity of cortical neurons, gradually strengthening the connections between them in order to consolidate a memory.

In animals, hippocampal and cortical replay have been observed in

REM and Non-REM (specifically slow-wave) sleep

Damage to the hippocampus prevents 

the formation of an episode

damage to the amygdala prevents

formation of an aversive association

HM’s Non-Declarative Memory

Unlike his episodic memory, HM’s procedural memory (ability to acquire new and complex motor skills) was completely intact

Thus, hippocampus does not play a role in

procedural memory

Procedural memory is acquired through

implicit, associative learning processes

The Law of Effect is an early description of how the consequences of an action change its likelihood:

• A given stimulus in the environment can elicit a variety of behavioral responses

  • If the outcome of one of those responses is ‘satisfying’ (Thorndike’s word), the connection between stimulus (S) and response (R) will be strengthened, making the response more likely to reoccur

  • if the outcome a particular response is ‘annoying’ (again, Thorndike’s word), the connection between stimulus (S) and response (R) will be weakened, making the response less likely to reoccur

Skinnerian Theory

BF Skinner built on Thorndike, introducing the terms ’reinforcement’ and ‘punishment’ to replace concepts of satisfaction and annoyance (Skinner was a pure behaviorist)

what is positive reinforcement ?

when behavior becomes more frequent because it results in the addition of an appetitive stimulus (i.e. something the animal will seek out or consume)

what is negative reinforcement?

when behavior becomes more frequent because it results in the removal of an aversive stimulus (i.e. something the animal will reduce contact with or avoid)

what is punishment?

when behavior becomes less frequent because of its results (can be positive, the addition of an aversive stimulus or negative, the removal of an appetitive stimulus)

What did Olds & Milner report in 1954 about electrical stimulation and reinforcement?

• Olds & Milner reported in ‘54 that electrical stimulation of the septum would positively reinforce a lever press

• Discovered accidently: they were aiming their electrode at a different part of the brain implicated in arousal.

  • They missed, hitting the septum

• They noticed that the rat kept returning to an area in an enclosure where electrical stimulation was delivered.

  • They then performed a lever-press experiment to formalize the reinforcing properties of septum stimulation

Rats will choose MFB stimulation over:

• food

• water

• sex

• their rat babies

Stimulation of the __________, on the other hand, is a powerful positive reinforcer

medial forebrain bundle (MFB)

How is a procedural memory acquired?

• The MFB is a fiber tract that carries the axons of dopamine neurons from the midbrain to the basal ganglia

What role do dopamine neurons play in reinforcement learning?

• Dopamine neurons will fire in response to the food early during training, when the animal is still learning, but not later, once the monkey knows the task.

  • This is called a reward prediction error (RPE), the dopamine neuron’s response to better-than-expected outcomes that plays an important role in reinforcement learning.

An RL algorithm needs only the following:

• The ability to produce an action

• The ability to detect key aspects of the environment

• The ability to produce a reinforcement signal when a goal state is detected (highly similar to a dopamine RPE)

• The ability to predict which actions will lead to the reinforcing goal state

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Synaptic plasticity hypothesis of memory

The prevailing hypothesis in the field is that memory is underpinned by synaptic plasticity:

persistent changes in the function of synapses

Synaptic plasticity hypothesis of memory

The hypothesis is that

some external event causes a change in the way neurons communicate, and that this change stores remembered information about that experience

In 1949, Don Hebb theorized the following form of synaptic modification:

If a presynaptic neuron repeatedly takes part in firing a neuron that is postsynaptic to it, then the connection between the two becomes strengthened 

Hebbian synapse allows:

“neurons that fire together to wire together”

Long-Term Potentiation (LTP)

Evidence for the Hebbian synapse was generated when Bliss & Lomo (1973) performed the following experiment in the hippocampus of rabbits:

• Placed a stimulating electrode in the preferent path, a major input to the dentate gyrus

• Placed a recording electrode in the dentate gyrus, to record the effects of performant path stimulation on the local field potential (LFP)

Long-Term Potentiation (LTP)

An excitatory LFP is a change in the

voltage of the extracellular fluid that occurs as positively charged ions enter neurons

Long-Term Potentiation (LTP)

An excitatory LFP indicates increased

synaptic stimulation and higher activity among the population of neurons around the recording electrode

LTP requires activation of

both NMDA and AMPA glutamate receptors

Bliss & Lomo, 1973

• Following strong stimulation, weak stimulation has a bigger effect on postsynaptic neurons

  • This demonstrates a ‘fire together, wire together’ synaptic mechanism

Spatial memory tasks like this one require the

hippocampus

Drugs that block NMDA or AMPA delivered directly into hippocampus can be used to test

whether LTP-like processes are important for hippocampal memory

What does blocking NMDA or AMPA receptors tell us about spatial memory?

Drug infusion right before rat finds food for the first time.
Bar graph is data from a later test of memory (after drugs wear off).
D-AP5 – NMDA blocker
CNQX – AMPA blocker
aCSF – artificial cerebrospinal fluid given to control subjects
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