I. What is this phenomenon of Plasticity?
Plasticity is a change in behavior, anatomy or electrophysiological response. For the sake of simplifying our discussion we will limit ourselves to the case of synaptic plasticity that is  induced by activation of inputs. This form of plasticity is referred to as activity dependent synaptic plasticity   and  is generally measured as a change in a evoked electrophysiological response.  It is contrasted by developmental plasticity, behavioral plasticity, injury induced plasticity and chemically induced plasticity which may be measured using behavioral or histological techniques.  We should note that non-activity dependent plasticities may in fact, after investigation, be fundamentally due to activity dependent synaptic plasticity and be subserved by the mechanisms uncovered in the investigation of activity dependent plasticity.

Evoked electrophysiological response -

• Transmitter release - Calcium regulation & various second messengers - refer back to discussion on Aplysia and the cerebellum
• extracellular space/synaptic cleft- neurotransmitter diffusion, removal of active compound from cleft
• binding to postsynaptic receptor and opening of channels
• change in relative electrical potential - measured either outside the cell (extracellular - population response - many cells) or inside the cell (intracellular - single cell- population of receptors). Responses that are depolarizing are excitatory postsynaptic potentials (EPSPs) those that are hyperpolarizing are referrred to IPSPs.  If they were recorded extracellularly they would be or shall I say should be denoted as population I/EPSPs (pEPSP, pIPSP)
• Interpretation of intracellular and extracellular responses. What do the upward and downward deflections represent? Remember that in extracelluar recordings IPSPs can be ignored and that most of the change in potential reflects the activation of EPSPs.  Diagram.

III.   Why do we think it might be occurring in the neocortex and hippocampus.
A. Synapses form in response to behavioral experinces likely to induce memories such as rearing in a complex environment.  This is shown as an increase in neocortical gray matter and while it relects a change  in many non-synaptic structures such as blood vessels and glia there definately seems to be more contacts onto neurons  (25% more).
B. Adult rats trained on a maze or motor task show increases in the number of synaptic contacts made onto a cell.  This effect can be lateralized suggesting that the phenomenon is not a general increase due to increased activity but a specific one related to the task that was learned.
C. Similar effects of rearing and training are seen across various species suggesting a common process that has been conserved over evolution.
D. Changes in response to rearing/occur rapidly and follow a time course similar to the behavioral phenomenon.
E.Developmental Plasticity is seen in these regions as a change in the width of ocular dominance column when visual input to one eye is interupted.
F.Activity dependent plasticity is seen in invertebrates (Aplysia) and subcortical regions in mammals (NMR).

IV. Since we already covered synaptic plasticity in the red nucleus corticorubral pathway, cerebellum parallel fibers - Purkinje cells, and Aplysia sensory - motor neuron why revisit?
A. All of the previous studies that demonstrated activity dependent plasticity  showed this phenomenon in subcortical regions and were using implicit/procedural tasks.
B. The most recent studies investigating more complex memory formation (explicit/declarative) suggest that   cortical not subcortical structures are involved.
 

V. Does the Hippocampus  show activity dependent plasticity?
Hippocampus- Not formally published and recognized until 1973 when Bliss and Lomo demonstrated increases in synaptic strength were elicited in response to either a 10-15 second,10-20 Hz  conditioning stimulation or a 3-4 sec, 100Hz conditioning. This work was done in anesthetized rabbits.  Test and Conditioning stimulation were delivered through the same electrode which was implanted in the Perforant Path.  Recordings were obtained from electrodes placed in the dentate gyrus.  This procedure was then replicated in the awake rabbit. Key features were the brief induction protocol, and the long-lasting nature of the change (10 hrs - 3days). The long-lasting nature of the change separated this phenomenon from augmentation, facilitation and short term potentiation and has since been named long-term enhancement, long-term potentiation (LTP) , long-lasting potentiation (LLE). Furthermore, this is a case of homosynaptic LTP because activity in the test pathway is critical for the induction of the plasticity.
 

IV. What have we learned since then?

A. Both increases (long-term potentiation - LTP ) and decreases (long-term depression-LTD) can be elicited in hippocampal tissue by physiologically relevant stimulation..

1. theta rhythms

200 Hz bursts at 200 msec intervals
2. low frequency <2 Hz

C. Co-operativity -

Nov 21
D. Associativity -

E. heterosynaptic effects -

Activity of presynaptic cell		Activity of post synaptic cell
		depolarization	hyperpolarization
	action potential	homosynaptic LTP	homosynaptic LTD
	no action potential	heterosynaptic LTP  (doesn't seem to occur)	Heterosynaptic LTD  (does occur)

 
 

F. Order Dependence  (pg93) - in line with classical and instrumental conditioning studies.

1. in vivo Levy & Steward, 1983 crossed weak pathway paired with strong stimulation of ipsilateral input.  If interval was over 200msec or if order was reversed there was  a slight depression.
2. in vitro Kelso & Brown, 1986- 2 weak inputs and 1 strong inputs stimulating a separate set of  Schaffer collaterals.
3. Dudai makes a point to discuss the reasons for not taking the idea of order dependency in the induction of activity dependent plasticity too far (pg 94).

 
H. Effects of different frequencies of presynaptic activity on homosynaptic activity dependent synaptic plasticity.  

1. Frequency - 200,100,50 LTP
5-20 no change
3- 1  LTD