Learning_2

Learning_2

1. Scoville & Milner 1957 patient HM no new declarative (episodic, spatial) LTM

   • Important for spatial learning (type of relational learning) (Morris water maze, 1982), (Kolb & Whishaw, 1996)
     • O'Keefe &Dostrovsky (1971) Cognitive mapping pyramidal cells in hippocampus make up map fire in familiar enviroment
       • Oltons & Samuelsons radial arms maze test- remove cues and they remember where they are
         • Sherry et al, hippocampus lesioned spatial task distrupted, Maguire taxi drivers larger hippocampus
           • Hippocampus important for spatial learning, evidence its consolidated to LTM by hippocampus

2. Amygdala

   • Intergrates components of fear as an emotional response: behavioural, autonomic and hormonal
     • Monkeys w/ damage to medial temporal lobe cease to show normal aggression or fear responses (Kluver & Bucy 1939) MTL damage affects our ability to feel emotion
       • Lesion just amygdala in rhesus monkeys no fear response (Dicks,1969)
         • Adolphs et al (1994) patient SM amygdala damaged most abilities intact trouble understanding facial expressions and emotional info
           • Bechara (1999) humans can be fear conditioned but amygdala damage blocked ability to acquire CR to CS
             • Adolphs et al (2005) patient SM does not look at eyes but when instructed to do so could then recognize fear. Need to see eyes to recognize fear.
   • Fear: Darwin (1872) innate, involuntary action, survival
     • Born deaf and blind can still laugh and cry
       • Elkman & Fruesen (1971) remote new guinea tribe able to recognise facial expressions
   • Shown to have primary role in memory and emotional (fear, aggression) reaction. Part of limbic system. Located in medial temporal lobe.
   • Role of amygdala in fear conditioning to study neural mechanisms of learning, you can LEARN a particular stimulus is threatening. Occurs quickly, long lasting
     • Conditioned stimulus in mice eg tone on its own no responses, unconditioned stimulus eg shock paired with CS, when CS presented alone fear response. learnt to fear tone. Philips and Le Doux (1992)
       • Galili et al (2011) even in drosophila they voluntairly go to less appealing odor not associated with shock, shows it has learnt lesson about odor conditioned with shocked
         • Can habituate fear conditioning, go back to no fear is CS keeps appearing with no shock (extinction). Can also just fear a context where US happened.
     • Philips and Le Doux (1992) if lesion hippocapmus in rats normal fear conditioning but less fear in contextual. If lesion amygdala no learning, important for fear conditioning
       • Pare, Quirk and Le Doux (2004) research indicates that the physical changes responsible for the classical conditioning of fear take place in the lateral nucleus of the amygdala
         • Morris et al (2001) Patient GY right cortically "blind", both sides of amygdala still activate when shown fearful face but couldn't say he saw a fearful face, damage to output from central nucleus?
           • Le Doux (1995) Amygdala recieves info into because sensory areas of thalamus project to lateral nucleus (LA) which passes it to BN and central nucleus, CE projects to hypothalamus, if you lesion thalamus animal cannot undergo fear conditioning
             • Campeau et al (1991) central nulceus most important for emotional response, when threatening stimuli percieved neurons in the CE are activated. Coover et al (1992) lesion to just CE animals take longer to learn possible shock is not worth pressing lever for food
               • HR increases neurons in amygdala firing more = changes in behaviour reflect changing in the cells
                 • Cells of the amygdala undergo LTP, pyramidal cells (neurons) in LA important for LTP
                   • Roagan & Le Doux (1995) Transmission of sensory (auditiory) info from thalamus to LA (thalamus and LA synapse with each other) is enhanced by high frequency stimulation strengthing the synapse or LTP, example of plasticity.
                     • Shinnick-Gallagher et al (1997) when fear conditioned, pryamidal cells are more responsive more firing synaptically (thalo-amygdala synapse)
                       • Maren (2006) with NMDA receptors blocked (preventing LTP) no fear conditioning, synaptic plasticity/LTP involved in forming new emotional memories or in other words LTP = learning.

3. Hippocampus

   • LTP mainly produced in CA1 region, on the dendritic spines of many pyramidal cells which contain high numbers of NMDA and AMPA receptors
     • Ca ion entering NMDA receptor activates CAMKII in dendrite which migrates to synapse resulting in more AMPA receptors. More AMPA receptors increase reponse to glutamate (neurotransmitter) = larger EPSP's = stronger synapse.
       • CAMKII critical for LTP. Silvia et al (1992), No LTP in CA1 field of mice with mutation of gene responsible for CAMKII
   • Role in memory. Part of limbic system. Located in medial temporal lobe.

4. Neurobiology of learning

   • Synaptic plasticity hypothesis: Strength of synaptic connections is modifiable by neural activity and learning may make use of this synaptic change
     • Hebb: cells associate over large brain areas to represent info/memory, caused by strengthtening of connections between neurons
       • Synaptic plasticity is foundation of learning
         • Alpysia 20,000 neurons. Kandel & Schwartz (1982) sensitization and habituation condition (learning) also change in synapse
           • Lomo (1966) intense stimulation of axons caused a long-term increase in strength of EPSP's in post-synaptic neuron. EPSP's must summate to depolarise the dendtrite spine. Synaptic strengthening/LTP occurs only when synapses are active while the post-synaptic cell is depolarised, Kelso et al (1986)
             • This is LTP, which appears to underlie synaptic plasticity, esp as a weak synapse is strengthened by a strong one if they are activated stimultaneously.
               • (1973) Bliss & Lomo LTP formed in hippocampus and other parts of brain

5. LTP learning?

   • Zola-morgan et al (1986) patient RB had missing CA1 hippocampal region, no to ability to form LTM (couldn't learn) is this because LTP couldn't happen?
     • Hippocampus dependent task (Morris water maze 1989) rats with D-AP5 NMDA receptor agonist (prevents some forms of LTP by blocking Ca ion passage) learned more slowly, may have relied on procedural learning rather than spatial (still learning). not sufficient proof LTP is neuro basis of learning
       • Complexity of hippocampal based learning has been unable to demonstrate directly that learning causes change in synaptic connections as a result of LTP. Move to simplier form of learning to test LTP fear conditioning

6. Memory consolidation in humans can takes years (Squire et al, 1975)