PSY290 - Lecture 6: Learning and Memory

learning

is a relatively permanent change in behavior resulting from experience

neuroplasticity

capacity of the nervous system for change

neuro

pertaining to the nervous system

plasticity

the quality of being easily shaped or molded

sequence of events

learning stimulus —> neuronal activity —> intracellular signaling pathways —> gene expression —> protein expression —> structural & functional changes

neuroplasticity is…

ubiquitous

neuroplasticity timeline

baseline —> brain activity during experience —> long-term result

what types of changes occur?

neuronal changes —> changes visible on the whole brain, the structure of neurons that is affected

changes in the strength of

synapses might be important for many behaviors

synapses are

modifiable

Hebb’s Postulate

when an axon of cell A is near enough to excite a cell B and repeatedly takes part in firing it, some growth process takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increases

synaptic strengthening

cell A gets better at activating cell B

Bliss + Lomo (1973)

showed that high-frequency stimulation of synaptic connections lead to a persistent increase in their strength

long-term potentiation (LTP)

model of learning thats favored, created by Bliss + Lomo within the hippocampus

features of long term potentiation

• experimentally induced by high-freq stimulation

• long-lasting, which makes it a suitable candidate for long-term memories

• correlated with memory in many animal models

• many forms (though post-synaptic is most studied)

long term potentiation is a widespread phenomenon

activity-dependent variations in synaptic strength such as LTP may be a fundamental mechanism by which we acquire and modify all behaviors

LTP is seen in

many parts of the nervous system including the cortex, striatum and spinal cord

long-term depression (LTD)

opposed process of LTP, also linked to memory, persistent reduction in synaptic strength and is generally induced by very prolonged weak stimulation

LTD in the cerebellum

has been proposed as a mechanism to explain motor learning

importance of LTD

• may also be an ‘erasure’ mechanism allowing for the resetting of synapses

• by resetting synapses, this may prevent saturation of excitation and allow for more flexibility in how neurons change over time

• may also help eliminate less useful synapses

beyond LTP

rather than focus on the stimulation itself, we can instead focus on the result of stimulation: the firing of action potentials

rate remapping

certain neurons change their firing rate w/ experience

population remapping

the neurons that fire will change w/experience

does neuroplasticity affect gray matter?

if the group of neurons thats being changed is large enough, we might see a visible change in gray matter when doing an imaging scan

taxi drivers

a study was conducted in London with taxi drivers to see if learning all the information of the streets effect the brain in a lasting way, the posterior hippocampus got larger

are functional differences possible?

• some people are introduced to music at an early age

• in musicians, areas of the somatosensory cortex that represent digits respond more strongly to stimulation

• effect is related to age of musical training

what is memory?

process whereby info is stored, consolidated and retrieved

diff types of memory

sensory, short term, long term, working

memory is not a

thing, it is a process

recreating a mental representation

(re)constructing memory

• memory is not passively retrieved but actively assembled

• we are not “seeing the past” but instead building a mental representation of it

• this process is influenced by our goals, expectations, knowledge and schemas

• this process is inaccurate

memory over time

memories for everyday + emotionally arousing events become inaccurate over time, through confidence arousing memories remains high

false memories

interventions can create memories that never happened (Loftus car accident experiment)

the interim period

inconsistent info can alter our memories while other interventions can create memories that never happened

memory in the brain

any one memory may be represented in a few cells

memory trace/engram

• a subset of cells representing a memory

• the engram is believed to include the cells that were active during the original experience

• the cells in the engram are interconnected; if you activate one cell you might activate them all

why only some cells in the engram?

• cells vary in excitability and plasticity, with some being highly excitable and highly plastic

• the excitability and plasticity at the time of experience is critical

• cells more excitable/plastic at the time of experience are more likely to be included in the engram

• “winner takes all” model (very competitive)

if the engram theory is correct…

then varying neuronal excitability and plasticity should affect the composition of the engram

how do we test the engram theory?

learning evoked changes in genes

learning evoked changes in genes

• events that change behavior (ie induce learning) due so by altering gene expression

• gene expression is regulated by transcription factors, which are activated by events associated w/ learning

• one transcription factor of interest is CREB

• cellular events associated w/ learning activate CREB

• CREB then activated other genes, altering overall protein expression

• if we artificially increase CREB expression, we might affect the chance a neuron is included in the engram

experimental support for learning evoked changes

• neurons overexpressing CREB are more active during fear memory training

• killing CREB-overexpressing neurons after the fear training impairs the fear memory

if two memories are accumulated at the same time…

the same set of neurons is likely to be highly excitable and plastic

linked and non linked memories

this may explain other phenomena, recall memories that are lumped closely together or related in time

if two memories involve the same cells…

may recall both at once or one after another

updating linked memories

change in one memory may lead to a change in the other

the search for engram

• Lashley measured memory in animals w/ cortical lesions

• memory impairment was correlated w/ extent of cortical damage

• no specific cortical region was important

where is memory stored?

• Lashley’s results suggested all of the cortex was important (not one area is key)

• Lashley missed important things that later proved the hippocampus to be a key part of memory

Lashley’s experimental flaws

did not address subcortical areas or consider multiple types of memory (long vs short vs working)

HM and the hippocampus

• hippocampus and adjoining areas surgically removed to treat epilepsy

• had anterograde amnesia from the point of injury

• proved the hippocampus was very much involved in memory

  • cannot create new declarative memories w/out hippocampus

amnesia

no new declarative memories

declarative memory

show by telling

episodic memory

a persons unique memory of an event from their perspective

semantic memory

knowing (facts)

standard memory consolidation

memories go through the hippocampus to long term storage, ability to form new memories is impacted when hippocampus is hurt

problems with standard memory consolidation

• recent data conflicts with the central proposal of SCT (that remote memories reside in the cortex)

• other patients with hippocampal damage (not HM) showed retrograde amnesia (sometimes ~3 years before injury)

• why would this retrograde memory loss occur if all remote memories were in the cortex?

• the multiple trace theory was proposed to address these issues

multiple trace theory

each time a rich, detailed (eg episodic) memory is recalled, the hippocampus lays down a new trace of it

hippocampus in memory

• the HPC is critical for memory acquisition, but is likely a gateway site rather than a storage site

• hippocampal involvement changes over time

• the hippocampus is not required for all forms of memory

hippocampus and consolidation theory

the hippocampus is involved in recent but not remote memories

hippocampus and multiple-trace theory

the hippocampus is important every time a remote episodic memory is reactivated if that memory is rich in detail

conditioning in animals

pairing a unconditioned stimulus with a neutral stimulus, then the neutral stimulus will evoke a conditioned response

conditioning in humans

conditioned stimulus + unconditioned stimulus = conditioned response

recognition memory processes

• linked to the perirhinal cortex

• recognition vs recall

• multiple choice is familiarity based

• perirhinal cortex is connected with recognition and familiarity

• perirhinal cortex lesions impair recognition

visual versus spatial memories

perirhinal cortex → recognition

hippocampus → space

depending upon the type of memory and the age of the memory…

different brain regions might be involved

improving acquisition

• activation of certain brain areas (eg entorhinal cortex) using electrodes can facilitate spatial memory

• neuroprosthesis

• related is the use of non-invasive measures of brain (eg TMS) to improve memory recall

• focus need not be limited to memory networks, but could target other systems that influence memory indirectly (eg attentional networks)

neuroprosthesis

the use of direct electrical stimulation (via implanted devices) to affect behavior and perhaps enhance memory

erasing a fear memory engram

we know how to delete a memory, but it is hard to find those specific cells that encode that memory + it could lead to long lasting effects if those cells do other stuff as well

creating false memories

• one study used a transgenic mouse model where active (ie engram) cells will express light-sensitive receptors

• first, animal is placed in context A (safe)

  • afterward, Engram A cells express light-sensitive receptors

• second, animal is placed in fear context B (unsafe)

  • during this time, Engram A cells activated with light

• finally, animal is returned to Context A

• animal now freezes in Context A (even tho context A was safe)

• weve turned the ‘safe memory’ of Context A into a ‘fear memory’ by manipulating the engram cells

modifying memories

• our memory for aversive experiences is generally good (certain details anyway)

• however, aversive memories can be highly disruptive to our lives (as in PTSD)

• can we treat PTSD by altering our aversive memories?

• if we appreciate how memory processing works, there may be an opportunity for intervention

• the amygdala adds ‘emotional valence’ to memories

• this effect is eliminated when the amygdala is damaged or beta-adrenergic receptors are pharmacologically blocked

beta-adrenergic receptor blocker

applied during reactivation of memories reduces PTSD symptoms