Exam 3: Learning and Memory

Synaptic Plasticity

Synaptic Plasticity

100 trillion snapses

• can be weak or strong

synaptic connectivity constantly changes in response

to activity and other factors

During development: synaptic connections

provides the basic “wiring” of the brain’s circuits

Throughout rest of life: synaptic connections

basis of “learning

Synaptic plasticity

may last from milliseconds to years

•short-term plasticity

change in the amount of NT released by the presynaptic neuron in response to an AP

• ability to change it's funciton •related to altered Ca++ levels in the axon terminal

• facilitation, augmentation, and potentiation

all forms of enhanced NT release -the neuron is releasing more NT than it would

• depression

a decrease in NT release •related to a decrease in the available NT vesicles

long-term plasticity

(~30 min to lifetime) -Long-term potentiation (LTP) / Long-term depression

• initially caused by post-translational modifications of existing proteins • e.g., upregulating glutamate receptors

long-term plasticity later sustained by.....

changes in gene expression creating new proteins

• • physical changes, including growth of new synapses etc (“structural”)

Learning

the process of acquiring new information

Memory

the process by which we store and retrieve / recall information

3 types of memory

sensory / short-term / long-term

3 processes of memory

encoding, storage, retrieval

• Encoding / Consolidation:

information from the environment is transduced into neural “codes” within the brain (sensation)

• Storage

retaining the information over time

• Retrieval

pulling the information out of storage

Encoding process

is a big mass of “interconnected” biological tissue • parallel and serial networks within massively parallel networks • sensations cause changes in spatiotemporal activity patterns of the cortex – we experience this as our “perception” of reality

Neurons and other areas that are active at the same time tend

to become more strongly connected (and vice versa)

Donald Hebb

"fire together / wire together” via functional and structural changes -• activity in 1 area is more likely to induce activity in connected areas

• Encoding/ Consolidation

transduction into neural code (spatiotemporal patterns of cortical activity)

Storage (biological basis or learning) -

long-term synaptic changes in cortical connections -• the biological basis of learning depends upon the ability of neurons to modify their synaptic connections within neural circuits based on experience

Storage involves the retention of....

Involves the retention of “information” through networks of associations –Connections between cortical areas –Auto-associative neural networks

Retrieval

• Gaining access to and being able to use information stored in memory • Reactivating cortical patterns

• Retrieval (memory) happens when

we re-experience similar spatiotemporal patterns in cortical activity

• Retrieval cue

any stimulus that is used to activate retrieval • Multiple cues work best • State (internal) and context (external) are important cues

Retrieval

• a neural network can process large amounts of information with only a small group of viable neurons • will yield output based on partial input • Many stimuli will induce memory of a person • One stimuli will elicit many memories

• Sensory (immediate)

artifact of sensory processing

• Short-term / working memory

functional changes (reverberating circuits, more / less NT)

• Long-term

physical changes (more / less terminals and dendrites) -• a behavioral continuum, but with distinct physiological processes

Sensory (Immediate) memory

• Holds incoming sensory information for very brief periods of time (seconds or less) • Artifact of sensory processing and the elicited patterns of cortical activity –“iconic” = visual sensory register –“echoic” = auditory sensory register

iconic

visual sensory register

echoic

auditory sensory register

Characteristics of Short term memory

duration, capacity

• Duration

• Duration = information only remains in STM for a short period of time (seconds to minutes)

Capacity

amount of information that can be held in STM is limited -Depends on the type of stimulus and the number of meaningful units, called chunks • ~5-7 chunks of info

Working memory (a type of STM)

• Small amounts of information held in memory for short periods of time – until distracted

Visual encoding (Working memory)

an image is formed in the mind • Activity in visual cortex

Phonological encoding (working memory)

auditory; based on sound • Activity in auditory cortex

Working memory

– higher order cognition - math etc • we can be consciously aware of the information, actively “keeping” it in STM (“working memory”)

working memory components

central executive, visual spatial memory, auditory memory

• “Central executive

Prefrontal cortex is directly connected to sensory areas, controlling these processes and directing activity within the brain

– Visual-spatial memory:

visuo-spatial sketchpad” involves forming mental images.

Auditory memory

phonological loop” involves repeating information to yourself

long term memory

Vast “library” of stored information and memories (patterns of cortical activity) •Unlimited capacity and duration •distinct cellular processes from STM

ways to get info into the LTM

Exposure and Rehearsal -Simple exposure to information, even many times, does not guarantee that it will get stored in LTM

Levels of Processing

Information that is processed more deeply will be remembered more easily later on

Declarative (Explicit) memories

relational knowledge –“explicit” - conscious, intentional memory retrieval –Divided into episodic and semantic memory.

Episodic memory (Declarative)

where and when info was learned

Semantic memory (Declarative)

general knowledge

1 trial learning

• Declarative memory

• something you can remember for the rest of your life a single event remembered forever

Procedural (implicit) memory (LTM)

skills and actions –“implicit” – memory can influence behavior without conscious awareness • - generally requires several trials to acquire

Forgetting.. this that can cause

• Encoding failure –Decay theory - not accessing on a regular basis –Interference –Motivated forgetting
 “Active” forgetting

Retrograde amnesia

memory loss for events prior to onset.

anterograde amnesia

memory loss for events after onset.

• inability to learn new things after injury

infantile amnesia

loss of childhood memories before the age of 2 or 3 years

• hard time remembering things before the hippocampus is wired up

• Neurons that fire together wire together (Hebb)

Multiple reactivation of spatiotemporal cortical patterns cause neuroplastic (functional / structural) changes to reinforce these patterns

• Different types of info are encoded by

different brain regions / processes:

procedural” info encoded by....

direct, multiple reactivations of sensory cortical patterns • along w/ basal ganglia & cerebellum

declarative info encoded by

by the sensory cortical patterns + hippocampus • “emotional” info from a declarative memory by the amygdala

the hippocampal formation

can be thought of as the highest level of association cortex -receives convergent inputs from all sensory areas

Hippocampus in Humans

S-shaped curved structure in the medial temporal lobe

Hippo campus in rodents

follows the curve of the lateral ventricle (more dorsal)

Areas of the cortex incluse

cortex, dentrate gyrus, ammon's horn (areas CA1-CA4), subiculum/presubiculum/parasubiculum, output pathways frorm the fimbria-forniz

Job of the Hippocampus

• inputs from the neocortex alter its circuitry to set up an “index” of cortical locations (long-term synaptic change) for the combined perceptual patterns that may make up a given memory

Role of the Hippocampus

• role of hippocampus is to initially “tie together” specific stimuli (“relationships” / context)

just like procedural memories, consolidation of perceptual associations into long-term memories in the cortex requires....

requires multiple activations -repeated or continual activation of a particular hippocampal index gradually strengthens the associations of cortical areas making up a memory

consolidation of perceptual associations in the hippocampus

probably takes place during sleep - rapid, looped replay -hippocampus is relaying the experiences -relaying the day you had over and over again

eventually, the cortex can generate the appropriate spatiotemporal patterns....

generate a memory without the hippocampus

bilateral hippocampal damage....

disrupts learning, memory formation and retrieval of recent “declarative” memories -severe / global anterograde amnesia, presumably for the rest of the individuals life • temporally graded retrograde amnesia, at some point they can recall stuff

what is spared with damage to the hippocampus

remote memories • immediate memory • perceptual / motor / cognitive functions (“procedural” memories) • may not remember learning the task, but when prodded to continue, they can perform at normal levels

Lateralized hippocampal damage: left

verbal material such as story content

lateralized hippocampal damage: righ

spatial tasks (localization of objects), facial recognition

memories older than about three years are not affected by hippocampectomy because....

the hippocampus is not necessary for retrieval or storage of older memories -those patterns have been activated enough that they don't need the hippocampus

Eric Kandel’s research with Aplysia shows...

• learning is a physiological process -gill withdrawal reflex (“reflex arc”) • siphon is an organ that takes in sea water • lightly brushing siphon causes gills to withdraw

snail model of habituation (Eric Kandel)

-40 BIG sensory neurons in siphon > 6 motor neurons in gill muscles (excitatory / glu)

• plus some excitatory / inhibitory interneurons

Kandel notices in the snail model of habituation

• continued stimulation causes this withdrawal reflex to habituate (response stops); demonstrates learning by stopping doing stuff

how is the animal learning that it does not need to be concerned?

-stimulation still produces APs in sensory neurons -BUT synaptic structures responsible for vesicle release are inactivated

• mobilization of transmitter vesicles is decreased -voltage dependent Ca++ channels become inactivated with repeated stimuli -• each sensory neuron AP releases fewer NT vesicles

decrease in response is learning

produces smaller EPSP in motor neurons & interneurons (functional change) • less likelihood of generating APs (and therefore gill withdrawal)

transient functional change in neural circuit =

short term memory

doing habituation repeatedly results

n a structural change of the axon terminals • some terminals totally retract

long term memory

• change in protein synthesis mediated by genes that maintain axon terminal structures loss of input causes postsynaptic dendritic arbor to shrink • reduced numbers of synaptic connections

forgetting

after several weeks of no stimulus, terminals start to grow back and system returns to baseline

sensitization

an increase in reflex magnitude -shock tail > brush siphon > stronger gill -involves same set of neurons with addition of modulatory interneurons from tail (more complex)

sensitization results in

release of more excitatory transmitter from sensory neurons onto the motor neurons (opposite of habituation)

Serotonin (aka 5-HT) from facilitating interneurons

binds to receptors on siphon sensory neuron axon terminals and creates changes inside the neuron that increase release of NT vesicles

At first: transient functional change (STM)

• repeated initiates a cascade of intracellular enzymatic events -CREB activates genes to synthesize proteins • neurotrophic factors (BDNF, NGF, etc )

more NT and/or receptors

structural changes - more axon terminal branches, neural connections, etc. (LTM)

for habituation and sensitizations -

LONG-TERM MEMORY REQUIRES MAKING NEW PROTEINS (prevented by drugs that inhibit protein synthesis)

Back to human model - tri-synaptic pathway

essentially a one-way avenue through the hippocampus • widespread cortical inputs and outputs • hippocampal circuits set up an “index” of activity patterns that initially “assists” in the cross-cortical association process

hippocampal circuits set up an “index” of activity patterns

that initially “assists” in the cross-cortical association process; now you can start to recall things easier and easier

How to study the hippocampus and it' s changes

placing the hippocampus in a Petri dish and electrically stimulating axons in the pathway will produce EPSPs in the CA1 pyramidal neurons (output cells)

• a high frequency (tetanic) burst of stimulation produces a long-lasting increase in EPSPs to subsequent, “normal” stimuli

• so, efficacy of synapse is enhanced (“potentiated”) by a single “experience

long term potentiation

the functional and structure of the neuronal synapses are changing in response to the EPSPS

LTP in general

occurs between neurons that use the “excitatory” amino acid glutamate (glu) • several types of postsynaptic glu receptors: • N-methyl-d-aspartate (NMDA) receptor-channels • non-NMDA

NMDA-type receptors

open ion channels BUT they are usually blocked by Mg++, so they don’t participate in EPSPs • NMDA receptors are “doubly-gated” ion channels (“associative”)

To pop Mg++ pug out and open Glutamate channel requires

requires EPSP of a high enough level allowing Ca++ (among other ions) into the dendrite • requires both NT and voltage (EPSP)

to avoid "saturation"

the opposing mechanism also exists (LTD)

• synaptic strength being depressed/ weaken