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....
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