Learning and Memory

• LEARNING = acquisitions of new knowledge or skills (adaptive)
• MEMORY = retention of learned information, linked to storage and retrieval
• BASIC CONCEPTS

  • decalritive (explicit)  facts + events
  • non-declarivtive (implicit)  habits/skills and associtative
  • hippocampus stores explicit memory

  1.  neurons --> place cells 
  2. fire at a high rate whenever the animal is in a specific location in the environment (place field)
  3. taxi driver had greater gray matter in the hippocampus compared to bus drivers and their no of years on the job correlated to it

  • cerebellum + basal ganglia (striatum, putamen) stores procedural memory
  • amygdala stores emotional responses
  • many regions of the cortext stores short and long-term explicit memory
• COGNITIVE MAP = an internal neural representation of the landscape in which an animal travels (birds + mammals)
• HOW MEMORY FORMS

  • SHORT TERM MEMORY

  1. last for seconds to hours
  2. repeition promotes retention
  3. limited capcity
  4. ‘labile’ --> sensitive to disruption
  5. does not require new ran or protein synthesis

  • LONG TERM MEMORY

  1. last for days to years
  2. unlimited capacity
  3. consolidated --> insensitive to disruption
  4. does require new RNA or protein synthesis

  • WORKING MWMORY --> used to hold info in mind

  1. sensory stimulus --> brain receives information
  2. encoding --> brain stores information
  3. storage --> brain retains information
  4. retrieval --> brain receives information + utilizes 
• HEBBIAN PLASTICITY = neurons that fire together wire together
• HOW LONG DOES LONG-TERM POTENTIATION WORK (lot)

  • ltp : persistent streghtening of synapses following high frequency stimulation of a chemical synase
  • long-lasting increase in signal transmitssion between two neurons 
  • one mechanism of synaptic plasticity
  • principal model of mechanisms underlying learning and memory
  • induction of ltp  artificial
  • carried out in slices of the hippocampus 
  • tetanus is applied onto the ca1 region of the hippocampus --> ltp is induced 
  • induced ltp requires tetanus stimulation + synapses undergone ltp have stronger responses to stimuli
• GLUTAMATE RECEPTORS

  • ampa receptors --> requires glutamate to open and allows sodium to influx
  • lmda receptors --> requires glutatmate, glycine and a depolarized cell to open and allows sodium and calcium to influx
  • increased ca --> acts as a second messenger 
• LTP MECHANISM

  • ampa and nmda receptors involved
  • presynaptic changes occurs --> neurotransmitter vesicle increases == increase in neurotransmitter release
  • post-synaptic changes --> increased dendritic are and sines --> increase sensitivity --> increase ampa receptors
• POSTSYNAPTIC MECHANISM

  • diverse signalling pathway involved
  • pka is also incolved
  • different converge on common targets
• LTP OR LEANING INDUCES MORPHOLOGICAL CHANGES IN DENDRITIC SPINES

  • level of dendritic spines + synase futon increased with ltp
  • increase in spine head volume and widening and shortening of spine neck
• LONG-TERM DEPRESSION (LTD)

  • synaptic transmission occurring at the same time as strong depolarization of the post synaptic neurons causes ltp of the active synapse
  • both are types of synaptic plasticity 
  • synaptic transmission occurring at the same time as a weak or modest depolarization of the postsynaptic neurons causes ltd of the actin synapses
  •  ltd is expressed by a long-lasting decreases in the fficiency of synaptic transmission
• LONG-TERM DEPRESSION (LTD)

  • weak stimulation --> ltd 

  1. amplitude will be lower than the start of the experiment

  • calcium influx through nmda receptor 
  • in ltp strong depolarization will lead to high levels of calcium
  • in ltd, weak depolarization will lead to small calcium influx

  
• PHYSIOLOGICAL FUNCTIONS OF LTD

  • hippocampus-dependent learning and memory (working and episodic memory, novelty detection)
  • fear conditioning in amygdala
  • recognition memory in perirhinal cortex
  • cerebellar learning 
• PATHOLOGICAL STATES LTD IS INVOLVED IN:

  • psychiatrics disorders (depression,schizophrenia)
  • drug addiction
  • mental retardation (fragile x syndrome)
  • neurodegenerative disease (alzheimers)
• MEMORY ISSUES- AMNESIA

  • loss of memories
  • often results form trauma
  • can be transient or permanent 
  • can be causes by damage to parts of the brain that are vital to memory processing

  1. concussing blow to the head

  • no cure
  •  retrograde and anterograde 

  1. antegroade --> difficulty learning new informatin
  2. retrograde --> diffifuclty remembering past information 

  • most famous --> atient hm
  • had a bilateral medial temporal lobe resection  led to anterograde amnesia
• MEMORY ISSUES- AMNESIA cont.

  • couldn’t remember anything after the operation 
  • could remember things pre surgery
  • helped discriminate between short vs long term memory and declarative vs non-declaritive
• DEMENTIA

  • group of symptoms affecting memory, thinking and social abilities
  • different causes 
  • alzheimers --> most common
  • more common in older people
  • progessive --> symptoms gets worse with time
  • different types of dementia 
  • different causes 
  • vascular dementia 
• APLYSIA

  • gastropod mollusk --> sea snail
  • lives on the coastal waters of California
  • only have 20000 neurons --> make it easy to study neuro
  • reddish brown snail, 15-30cm in length
  • breathes through the gill
  • have been used to study simple forms of learning due to their withdrawal reflect

  1. tactile stimulus 
  2. protective reflex protects the animals from predators

  • 2 types of leaning:

  1. non-associative learning
  2. associative learning
• NON-ASSOCIATIVE LEARNING IN APLYSIA

  • change in an animals behaviour as a function of ecpeirence with a particular kind of stimuli
  • no temporal stimuli with stimulus and response
  • habituation : loss of response because of repeated stimulus
  • dishabituation : recovery of innate response 
  • movement of gill is recorded in response to a specific stimulus
  •  respond was habituated when stimuli was given after 6 times 
  • when a strong stimulus is given between the 13-14 stimuli, gill response is storng again (dishabituation)
• SENSITIZATION = response is stronger than normal
• ASSOCIATE LEARNING IN APLYSIA

  • classical conditioning- pavlova experiments

  1. dog associates hearing the bell and food --> salivating (when they heard the bell --> it starts to salivate)
  2. food is unconditioned stimulus (dogs showed unconditioned response)
  3. bell is conditioned stimulus --> new stimulus we are trying to link (dog showed conditioned response)

  • In applysia:

  1. tail shock is used as unconditioned stimulus
  2. siphon stimulus was used as a conditioned stimulus
• LONG TERM MEMORY IN APLYSIA

  • short term --> hours
  • long term memory --> days, week
  • distributed training and massed training 
  • distributed --> 10 trials every day for 4 days
  • massed --> all 40 trials in one day
  • distrubted > massed
  • aplysia showed long-term memory for habituation 
  • aplysia showed long term memory for sensitization 
• APLYSIA NERVOUS SYSTEM

  • consists of fanglia 
  • ganglia communicate through connectives (anatomical pathway)
  • ganglia arranged in bilaterally symmetrical pairs abdominal ganglion is unpaired

  1. controls heart rate, blood circulation and repsiratoin
  2. contains primary sensory neruons, interneurons and motor neurons involved in the gill + siphon withdrawls reflex
• SYNAPTIC ANALYSIS OF LEARNING

  • Presynaptic facilitation

  1. influx of calcium --> release of transmitter --> epsp is formed
  2. tail shock induces a spike broadening --> more ca + more transmmitters --> increases epsp

  • importance of serotonin

  1. critical role in sensitization --> presynaptic facilitation
  2. serotonin induces facilitation --> increases sensory neuron excitability, motor nueorn epse and reflect amplitude
• BIOPHYSICAL ANALYSIS OF LEARNING

  • serotonin temporarily closes potassium channels (s-current) in sensory neurons
  • outward potassium current is slowed --> net effect is prologation of the action potential or spike broadening 
  • repolarization of membrane is slowed --> spike broadening
  • increases calcium influx --> increase transmitter release --> enhance excitability
• MOLECULAR ANALYSIS OF LEARNING

  • camp acts as a second messenger
  •  camp activates pka
  • active pka phosphorylates substrates protein 
  • serotonin increases camp in the sensory neurons 
  • inhibition of pka caused inhibition despite broadening and decreseed excitability 
• MECHANISTIC ANALYSIS OF LONG TERM MEMORY

  • repeated serotonin or camp in the sensory neuron leads to ersistent phosphorylation of pre-existing proteins + synthesis of new prtines
  • causes long term increase in synaptic facilitation
  • causes long term increase in synaptic transmission
  • causes dramatic growth of sensory neuron processes  long term memory for senstisation
• SYNAPTIC FACILITATION REQUIRES POSTYSYNAPTIC PROTEIN SYNTHESIS

  • serotonin added to dish --> size of the moto neurons increases
  • if gellin (protein inhibitor) --> long term response is decreased

  1. short term facilitation does not require post-synaptic protein synthesis