Module 9: Learning and Memory

Stimulus-Response Learning

Learning refers to the process by which experience change our nervous system and behaviour

Memory refers to long-term changes in the nervous system following learning

Stimulus-Response Learning occurs when people respond in a certain way when shown a particular stimulus

Classical Conditioning

• Every time Joy sees ice cream, she salivates. The ice cream is an unconditioned stimulus that results in an unconditioned response (salivating)

• There is a food truck that drives past Joy’s house. Each time it passes the house, it plays a distinctive tune. The song is a neutral stimulus.

• For several weeks, every time the truck drives by the house, Joy’s parents buy her an ice cream. Here the neutral stimuli is paired with the unconditioned stimulus

• Eventually, whenever Joy hears the song played by the food truck, she automatically salivates. The song has become a conditioned stimulus that causes a conditioned response (salivation)

Eye-Blink Conditioning

In eye-blink conditioning, a puff of air (US) causes the eye to blink (UR). The puff of air is paired with a tone (CS) for several trials. After a number of pairings, the tone itself elicits a blink (CR).

What is happening at the neural level?

The somatosensory system detects the puff of air; The auditory system detects the audio tone; The motor system controls the eye blink response

• A tone presented alone will not cause the motor system to generate an eye blink because the connection between the auditory neuron and the motor neuron is weak

• An air puff alone will cause the motor system to generate an eye blink because the connection between the somatosensory neuron and the motor neuron is strong

Hebbian Rule of Learning: Neurons that fire together, wire together

• Therefore, the more simultaneous administrations of stimuli, the stronger the synapse between the auditory neuron and motor neuron.

Conditioned Emotional Response

Via classical conditioning, neutral stimuli can be paired with fear evoking stimuli to generate a Conditioned Emotional Response (CER). Physical changes for producing CERs likely occur in the lateral nucleus of the amygdala which then projects to the central nucleus.

Example:

US: aversive loud sound

Neutral Stimulus: train approaching

After several repetitions of a loud sound occurring when train approaches, develops CER

CS: train

CR: fear

Auditory neurons form strong synapses with the lateral nucleus neurons. Activated lateral nucleus neurons send information to the central nucleus to evoke an (un)conditioned, automatic emotional response.

After several repetitions of simultaneous occurrence of US and NS, the synapses between the visual neurons and lateral nucleus neurons become stronger and stronger, eventually generating its own conditioned response, which is sent to the central nucleus.

Long-Term Potentiation: the number of receptors on the post-synaptic cell increases

Long-term changes in glutamate system increase the EPSPs sent to post-synaptic cells in amygdala. Blocking long-term potentiation in the lateral nucleus stopped establishment of CERs.

Operant Conditioning

In operant conditioning consequences and outcomes shape behaviour

Reinforcers are consequences that increase the likelihood of repeating behaviour

Punishers are consequences that reduce the likelihood of repeating behaviour

Involves strengthening the connection between neural circuits that detect a particular stimulus and neural circuits that produce a particular response.

Reinforcement

In response to reinforcers and punishers, reinforcement mechanisms in the brain become active to establish long-lasting synaptic changes.

Dopaminergic neurons play a very important role in reinforcement via the mesolimbic system and the mesocortical system

The mesolimbic system begins in the Ventral Tegmental Area (VTA) of the midbrain and sends information to the amygdala, hippocampus, and Nucleus Accumbens (NAC) of the basal forebrain. The NAC sends information to the basal ganglia.

Dopaminergic activity in NAC is thought to shape reinforcement. Cocaine or amphetamine administration increases dopamine release in the NAC. Reinforcers such as water and food also increase dopamine release in the NAC

Role of Basal Ganglia

Circuits responsible for operant conditioning begin in the sensory association cortex (perception)and end in the motor association cortex (movements)

Two major pathways:

• Direct transcortical connections

• Connections via the basal ganglia and thalamus

Direct Transcortical Connections:

• Connections from one area in cerebral cortex to another

• Involved in acquiring episodic memories and complex behaviours that involve deliberation or instruction

• A memorised set of rules provides a script to follow

Basal Ganglia Pathway

• As learned behaviours become automatic and routine, they are transferred to the basal ganglia

• Frees up the transcortical circuits

• No longer need to deliberately think through each step

What is happening on the neural level?

• The neostriatum (caudate and putamen) of the basal ganglia receives sensory info from all regions of the cerebral cortex, as well as info about planned movements from the frontal lobes

• The neostriatum projects to another part of the basal ganglia called the globus pallidus.

• The globus pallidus projects to the premotor and supplementary motor cortex (movement planning) and then to the primary motor cortex (movement execution)

Motor and Perceptual Learning

Perceptual Learning

Refers to learning to recognise a particular stimulus. It is thought to occur via changes in sensory association cortex. For example, we learn to categorise different objects into different groups (furniture, people, family, etc.) Perceptual Learning is related to each of our senses.

The primary visual cortex receives information from the Lateral Geniculate Nucleus (LGN) of the thalamus and sends it to the extrastriate cortex (sensory association cortex)

• Ventral Stream projects to inferior temporal cortex (object recognition)

• Dorsal Stream projects to posterior parietal cortex (perception of object location)

Damage to inferior temporal cortex disrupts the ability to discriminate among visual stimuli, but also disrupts the memories of the visual properties of familiar stimuli

Specific kinds of visual information can activate specific regions of the extrastriate cortex

• MT/MST responsible for movement perception

Motor Learning

Refers to learning to make new response via motor circuits in the brain. Importantly when we are learning new responses, we usually do so in response to some sensory information (external stimulus). For example, when learning to drive, we must learn how to interact with a gearstick, the steering wheel, and the foot pedals.

• Supplementary motor area: helps individuals execute automatic movements that have previously been learned.

• Premotor cortex: helps motor learning that is informed by sensation.

• Ventral premotor cortex: contains mirror neurons which aid learning via observation. They fire when we watch another person execute a particular movement.

Basal Ganglia plays an important role in stimulus-response and motor learning, particularly where motor executions become automatic (Huntington’s)

Between Session Learning: after initial rapid increase in performance on a new learned skill, the motor memory for the movement will continue to improve even in the absence of practicing

Conditioning strengthens the connection between Perceptual and Motor learning!

Memory and Relational Learning

Relational learning refers to learning about the relationships between different stimuli

Episodic learning involves remembering sequences of events that we witness (e.g. each thing we did on a given day)

Types of Memory

Sensory Memory

• A brief period of time that the initial sensation of the environmental stimuli is remembered

• Length varies from fractions of a second to a few seconds

• Occurs in each of the senses

Short-Term Memory

• Contains information from sensory memory only if its meaningful or salient enough

• Length ranges from seconds to minutes - rehearsal

• Capacity is limited to a few items (4-7) - chunking

Long-Term Memory

• Contains information from short-term-memory that is consolidated

• Relatively permanent

• Lasts for minutes, hours, days, or decades

• Strengthened with increased retrieval

• Two major categories: Declarative and Non-Declarative

Non-Declarative (Implicit): memories that we are not necessarily conscious of, operated automatically, and controls motor behaviours

Declarative (Explicit): memory of events and facts that we can think of and talk about, includes episodic memories (context), and semantic memories (facts)

Semantic Memory: involves facts, but not information about the context in which the facts were learned - stored in neocortex - anterolateral temporal lobe

    Semantic Dementia: semantic information is lost, but episodic memory for recent events may be spared

Spatial Memories: people with anterograde amnesia are unable to consolidate information about locations of things in their environment; can occur bilaterally (medial temporal lobe), but also when only right hemisphere is affected

    Right hippocampal formation becomes active in navigation tasks

Hippocampus and Memory

Based on H.M.'s case (Henry Molaison), when the hippocampus is removed:

• Severe anterograde amnesia: He couldn't form new explicit (declarative) memories after surgery.

• Intact procedural memory: He could learn new motor skills (e.g. mirror drawing) but didn’t remember learning them.

• Old memories mostly intact: Memories from before the surgery were mostly preserved.

• Showed that the hippocampus is crucial for forming new long-term declarative memories, but not for storing old memories or procedural learning.

• Hippocampus receives information about what is happening from sensory and motor association cortex, as well as basal ganglia and amygdala

• Via efferent connections with the same regions, the hippocampus modifies the memories that are being consolidated, linking them together in ways that will permit us to remember relationships among the elements of the memory

• Evidence shows that retrieval of younger long-term memories uses hippocampus more, than older long-term memories

Animal research, especially in rodents, shows that the hippocampus is critical for relational learning—the ability to form associations between multiple elements of an experience.

Key findings:

• In Morris water maze experiments, rats with hippocampal lesions can’t learn the spatial relationship between cues in the room and the hidden platform’s location. This shows the hippocampus helps link different pieces of information to form a cognitive map.

• In object-place or contextual fear conditioning tasks, animals with hippocampal damage struggle to associate objects with locations or contexts with aversive events, showing impaired relational learning.

• The hippocampus allows animals to flexibly use relationships between stimuli rather than just learning simple stimulus-response patterns.

In short, animal studies demonstrate that the hippocampus supports learning that involves linking multiple cues, places, or events into a meaningful whole.

Anterograde Amnesia

Anterograde amnesiacs cannot remember things after lesion to the brain

Retrograde amnesiacs cannot recall events before the lesion took place

Based on HM’s case Milner has found that the hippocampus is involved in converting immediate short-term memories into long-term memories. However it was not the location of either of those, nor was it necessary for retrieval of long-term memories.

Anterogarde amnesiacs are spared in terms of Perceptual, Stimulus-Response, and Motor types of learning. Declarative memory is completely absent, whereas non-declarative memory is present.

Long-Term Potentiation

Long-Term Potentiation (LTP) is a long term increase in the excitability of a neuron to a particular input caused by repeated high frequency activity of that input.

• Requires activation of synapses

• Requires depolarisation of the post-synaptic neuron

Hippocampal formation inlcudes:

• The hippocampus (which contains CA3 and CA1
  neurons pictured)

• The perforant path

• The dentate gyrus

• The entorhinal cortex

• The subicular comple

• The primary input to the hippocampal formation comes from the entorhinal cortex

• Axons from entorhinal neurons pass through the perforant path and form synapses with cells in the dentate gyrus

• Dentate gyrus cells then project to region of the hippocampus called CA3.

• The CA3 neurons then synapse with CA1 neurons which then project back to the entorhinal cortex and make a loop

Long-Term Potentiation (LTP) is a long-lasting increase in the strength of synaptic transmission and is widely considered a key mechanism underlying learning and memory, especially in the hippocampus.

NMDA receptors are blocked by magnesium ions unless the dendritic spines of the postsynaptic cell are already depolarized. This can occur via high frequency action potentials causing increased release of glutamate from the presynaptic cell, and, subsequently, more sodium ions entering into the cell via AMPA receptors.

Key Features of LTP:

• Triggered by high-frequency stimulation of a synapse (e.g., tetanus).

• Specific to activated synapses—only the stimulated connection is strengthened.

• Associative—if a weak input is active at the same time as a strong input, it can also become potentiated (Hebbian learning).

Cellular Mechanism (typical in hippocampus, e.g., CA1 region):

1. Glutamate release from the presynaptic neuron.

2. Glutamate binds to AMPA and NMDA receptors on the postsynaptic neuron.

3. AMPA receptors allow Na⁺ influx, causing depolarization.

4. If depolarization is strong enough (e.g., due to high-frequency input), Mg²⁺ block is removed from NMDA receptors, allowing Ca²⁺ to enter.

5. Ca²⁺ influx activates intracellular signaling cascades (e.g., CaMKII, PKC).

6. These signals:

   • Insert more AMPA receptors into the postsynaptic membrane (increasing sensitivity).

   • Strengthen synaptic structure and function.

   • May trigger gene transcription for long-term changes (via CREB activation).

Effects:

• Increased synaptic strength and efficacy.

• Can last hours to weeks or longer, depending on conditions and reinforcement.

• Thought to underlie memory consolidation and associative learning.

Summary:

LTP strengthens synapses based on activity patterns, following the principle that "neurons that fire together, wire together." It depends heavily on NMDA receptor activity and calcium signalling, and it's crucial for forming long-term memories.