Part VII LEARNING

A. Pavlov's Cortical Model

B. Lashley's Cortex Lesion tests
	1. Mass action & equipotentiality
	2.  Redundant cortical specialization

C. Cerebellar & Hippocampal Lesions
	1. Cerebellum and simple S-R conditioning
	2.  Hippocampus
		a. Failure on spatial and higher order conditioning
		b. Human anterograde amnesia

D.  Learning in simple neural systems
	1. Headless spines and ganglia
	2. Cellular mechanisms in aplysia
	3. Hippocampal long term potentiation:
		a cellular model for learning in mammals	
	
READING : : Kalat Chapt 13 

Pavlov posited that the formation of associations created new cortical connections.  In this way, he thought a CS could actually trigger UCS neurons in the cortical area that corresponded to it (e.g., taste of food).
Some evidence for his position comes from cortical electrophysiology.

However, as Lashley demonstrated, no area of the cortex is not needed for basic learning of classical or instrumental responses.  Instead, Lashley suggested the cortical principles of equipotentiality (all regions can mediate learning equally) and mass action (ability to learn is proportional to amount of cortex available).

Although Lashley was wrong  about cortex specialization, he was right that most learning and memory seems to involve subcortical mechanisms rather than cortex.  Two subcortical structures are especially important.
1  CEREBELLUM   Nucleus Interpositus 
2  HIPPOCAMPUS

Evidence:
-cerebellar lesions block simple  s-r conditioning and motor learning
- Hippocampal lesions block learning of stimuli correlations (as opposed to simple contiguity), conditional discriminations, and spatial relations in animals.  In humans, hippocampal lesions also produce anterograde amnesia for declarative forms of learning (H.M., Korsakoff's syndrome).

Damage to a circuit involving the hippocampus may also be responsible for the memory deficits of Alzheimer's disease.  Cortical plaques and damage to the basal forebrain nucleus (which contains acetylcholine) disrupt a hippocampus-mamillary body - basal nucleus - cortical system, in which loss of any component produces similar symptoms

How do neurons learn?
The persistence of learning in 'decapitated cockroaches' and isolated Aplysia nervous systems demonstrates that relatively few neurons are needed for a system to show basic learning.  In Aplysia, we can see the actual synaptic and neural mechanisms that mediate three kinds of simple learning: habituation, sensitization, and classical (Pavlovian) conditioning.
1. Habituation:  
	Repeated innocuous stimulus elicits diminished presynaptic neurotransmitter release from sensory neuron on later presentations.  The decline in response is specific to the eliciting stimulus.
2. Sensitization
	A noxious stimulus releases serotonin onto the original sensory (innocuous stimulus) neuron.  Serotonin blocks K+ gates, and prolongs action potential in the original sensory neuron.  This allows more CA++ to enter the neuron, which increases neurotransmitter release.
3. Conditioning
	Requires correlation of the CS (innocuous stimulus) and UCS (noxious stimulus).  If UCS serotonin arrives immediately following a CS-elicited action potential, there is a synergy in the effect on K+ gates.  An even greater potentiation of Ca++ influx and neurotransmitter release occurs. 

Neuronal learning in the mammalian hippocampus.
Long term potentiation (LTP)
	Primary postsynaptic mechanism:
	a.  A burst of action potentials elicited by a conditioning stimulus (glutamate) increases cell Ca++ concentration
	b. [Ca+] concentration activates calpain protein (a second messenger system)
	c. cascade changes membrane to expose NMDA glutamate receptors 
	d. the next release of glutamate has a larger effect on the postsynaptic neuron
Thus both hippocampal LTP and aplysia learning involve Ca++ mediated changes in intra-neuronal responsiveness, and enhancement of neurotransmitter effects.