Learning and Memory

Nature of Learning

Associative Learning: Typically includes most forms of stimulus-stimulus and stimulus-response learning.
Probably is responsible for all learning.
Basically, when you perceive a stimulus, it either makes you more likely to think of something else (stimulus-stimulus) or it makes you more likely to respond in some way (stimulus-response)

Non-Associative Learning: Often refers to the phenomena of habituation and sensitization, which are when you start to respond differently to a stimulus just because you have perceived (seen it, smelled it, etc) some number of times before.
(E.g. if a stimulus is neutral and without predictive value, animals habituate to it)

Synaptic plasticity = changes in the structure or biochemistry of synapses that alters the strength of the synaptic connections.

LTP (Long-Term Potentiation) = the phenomenon by which EPSPs become stronger in a long-term, stable manner.

We can induced LTP if we stimulate the perforant path with high intensity, high frequency stimulation

Hippocampal formation = Forebrain structure of temporal lobe, constituting an important part of limbic system.
Includes the CAI, II, III, as well as dentate gyrus and subiculum.

Mechanisms of Synaptic Plasticty

NMDA receptor: Inotropic glutamate receptor that is blocked by Mg2+ ions when a cell is hyperpolarized.
It only opens when both glutamate binds to it and the voltage of the cell is depolarized.
It lets in both sodium and calcium.

Calcium is key to synaptic plasticity

CaMKII: Type II calcium-calmodulin kinase.

It is an enzyme that is activated by calcium influx through NMDA receptors.

It plays a role in the intracellular signaling cascade that establishes long-term potentiation, which is typically an increase in the number of AMPA receptors in the synapse.

AMPA receptor: Inotropic glutamate receptor that depolarizes neurons when glutamate binds by letting sodium ions in

When open, it produces EPSP

Pre-synaptic Plasticity

NO (Nitric oxide synthase): Enzyme responsible for the production of nitric oxide (often released from a post-synaptic synapse)
Several experiments suggest that NO may be retrograde messenger that contributes to formation of LTP.

LTD (Long-term depression): Long-term decrease in the strength of the connection between 2 neurons (synaptic strength). Low-frequency activity in the inputs to a quiet neuron (in the synapses) can decrease the strength of the active synapses. LTD is often mediated by endocannabinoid signaling, from postsynaptic neuron to presynaptic neuron.

Associative Long-term potentiation: The increase in synaptic strength that occurs in weak synapses when they are active right around the time when stronger inputs caused the postsynaptic neuron to spike.

Hebb's rule: Hypothesis proposed by Donald Hebb that the cellular basis of learning involves the strengthening of synaptic connections that are active when the postsynaptic neuron fires an action potential.

This is known as: "Fire together, wire together... more strongly than before. The synaptic connection does have to initially exist"

Four basic forms of Learning

Declarative (Explicit) Memory: a memory that can be verbally expressed such as facts and personal events. Memory that can be consciously accessed

Declarative Memory Tasks: remembering past experiences, learning new words, finding way new environment

Non-declarative (Implicit) Memory: unconscious memory whose formation does not depend on the hippocampal formation; a collective term for perceptual, stimulus-response, and motor memory.

Nondeclarative Memory Tasks:
- Perceptual Learning: Broken drawings, Recognizing Faces (also stimulus-response learning), recognizing melodies
- Stimulus-response learning: Classical conditioning (eye blink), Instrumental conditioning (choose circle)
- Motor learning: Sequence of button presses

Relational Learning (stimulus-stimulus learning)
Def: learning relationships among individual stimuli.

it's the basis of declarative memory. both episodic and semantic
largely dependent on the hippocampus and neocortex
linked to spacial memory: the Morris water maze requires relational to navigate around the maze

Perceptual Learning (e.g. associative learning)
Def: learning to recognize particular stimulus. The ability to recognize stimuli that have been perceived before.

Largely dependent on neocortex-sensory association areas
The basis of recognition and categorization
enables us to recognize and identify objects or situations, which improves our to respond appropriately
allows us to recognize changes or variations in familiar stimuli and respond to those changes
One of 1st perceptual learning is Language
Spared learning ability when hippocampus damage and anterograde amnesia.

Motor Learning (procedural learning)
(similar to perceptual learning but has to do with motor part)
Def: learning to make skilled movements

the basis of motor skills (bike riding, ball throwing, etc..)
Involves different brain areas involved in movement
- we get feedback from our movement from out joints, vestibular system, eyes, ears and everything else --> we use this information to improve our movements
Spared learning ability when hippocampus damage and anterograde amnesia
Example for motor learning: Sequence of button presses

Stimulus-Response learning (implicit and explicit memory)
Def: learning to automatically make a particular stimulus.

The basis of Classical (Pavlovian) & Instrument (Operant) conditioning

Involves different brain areas depending on the stimulus and response
Example of Nondeclarative Memory tasks: Classical conditioning (eye blink), Instrumental conditioning (choose circle & maybe recognizing faces)

Psychology terminology

UR (unconditioned response):a behavior that spontaneously, naturally occurs in response to a U.S.

CS (Conditioned Stimulus): an initially meaningless, neutral stimulus that becomes associated with an unconditioned stimulus (e.g. a bell or light that can be used to predict food delivery)
E.g. the CS can be a tone

CS leads to CR

US (Unconditioned Stimulus): something that has inherent value to an animal, like a food reward or an electric shock. There is no learning (conditioning) involved with an unconditioned stimulus. It is what it is. (US = aversive)

CR (Conditioned Response): a behavior that occurs in response to a CS.
This behavior is often (but not always) similar to the UR that follows the US that was associated during the training with the CS.

Spatial Perception and Learning

Place Cells = different neurons have different receptive fields; for example, they fire when the rat was in a specific place.

EPSPs = Excitatory postsynaptic potentials and membrane depolarizations used by evoked activity in some number of inputs (synapses).

Lesion to hippocampus and Amnesia

Retrograde amnesia: inability to remember events that occurred 'before' the brain injury.

Complete amnesia: in either direction is rare

Anterograde amnesia: refers to the inability to learn new information 'after' brain injury. Memory for events that occurred before the injury remain intact.

Korsakoff's syndrome: Permanent anterograde amnesia caused by brain injury, usually resulting from chronic alcoholism.
Korsakoff's patients are unable to form new memories but can still remember old ones efore the brain damage occurred.

Confabulation: reporting of memories of an event that did not take place without the intention to deceive. (usually, brain tries to fill in the gap)

Seen in people with Korsakoff's syndrome.

Instrumental Conditioning (Operant conditioning): learning that occurs in response to reinforcement, in response to consequences. The likelihood of you repeating an action depends on whether oy was [trviously punished or reinforced.
Requires that animal moves, make decisions (unlike classical conditioning).
In contrast to classical (Pavlovian) learning, operant conditioning requires that the animal can move and make decisions. It promotes learned and thought processing

Reinforcement

Reinforcing stimulus: Appetitive stimulus that follows particular behavior and makes behavior and makes behavior become more frequent.

Simple Neural Model of Instrumental Conditioning:
stimulus --> neural circuit that detects a particular stimulus (Perceptual System) --> Neural circuit that controls a particular behavior (Motor System) --> Behavior (e.g. lever press) --> reinforcing stimulus (e.g. food) --> reinforcement system --> back again to neural circuit that controls a particular behavior (Motor System) through a reinforcement system which strengthens this connection

Punishing stimulus: Aversive stimulus that flows particular behavior and makes behavior become less frequent.

Role of the Basal Ganglia

there are two major pathways between sensory association cortex and motor association cortex

Direct Transcortical Connections: connections from one area of the cerebral cortex to another (from one cortical to another one)

Connections via Basal Ganglia and Thalamus: Synaptic strength is the basal ganglia is heavily dependent on the dopaminergic reinforcement learning signal, so this area is the primary location for instrumental conditioning.

Neural circuits involved in Reinforcement:

VTA (Vental tegmental area):

group of dopaminergic neurons in the midbrain whose axons primarily project to the ventral striatum (nucleus accumbent)
Dopamine release is a reinforcement signal

Nucleus accumbens:

Nucleus of ventral striatum (basal forebrain) near PFC
Receives dopaminergic inputs from the ventral segmental area and is thought to be involved in goal selection

Episodic memory: personal experiences associated with a time and place. Autobiographical memory.

Semantic memory: a memory of facts and general information. This knowledge doesn't need to be associated with time or place in which we learned the information

Grid cells = the size of each grid-based hotspot and the distance between these spots is a stable feature of grid cells.
However, the neural activity of neurons located deeper and deeper in the hippocampus (along with the dorsoventral extent of some hippocampal areas) corresponds to larger and larger location-based grids.

Border Cells: fire when an animal is near one or more boundaries of environment, such as walls of a box.

Hippocampal lesions: disrupt the ability to keep track of and remember spatial locations.

For example, the Morris water maze requires relational learning to navigate around the maze.
- Animals get their bearings from relative locations of stimuli located outside the maze - furniture, windows, doors, and so on
  - Mazes can also be used for non-relational, stimulus-response learning

Basal Ganglia dependent learning: has to do with implicit learning, also thought to be a movement selection filter (whether the movement is worth it or not)
Without dopamine, the animal can move but choses not to (still engages in reflexive movement and swimming to prevent drowning) so the animal moves randomly and doesn't't reach the platform

Head direction Cells

Memory encoding: Maybe for every new envenom every new moment in your life, presumably, there is a somewhat unique collection of active grid cells and place cells (or at least a unique pattern of activity in these cells) in your hippocampal structures.

Memory encoding pathway:
Cortical sensory systems --> Hippocampus

Memory retrieval event:
Partial cue (thing about many memories come in) --> Hippocampus (here you think about more specific things) --> cortical sensory systems (you think about a lot of things associated with this memory)