Long-term potentiation (LTP)

Demonstration of LTP in hippocampal neurons

Perforant path, mossy fibers

Properties of LTP

Induced by brief stimulation, input specificity, cooperativity, associability

Neurochemical mechanisms (review)

Long-term depression (LTD)

Low freq. stim.-->LTD, high freq. stim-->LTP

May prevent saturation

Long-term mechanisms yield structural modifications

Pharmacological studies

Antagonists: APV (AP5) and MK-801

Affect induction, not expression

Impact on spatial learning

Impact on fear conditioning (Fanselow)

Genetic manipulations

Techniques

Gene targeting

Making a knock-out mouse

Making a transgenic mouse

Evidence

Impact of knocking out CaMKII (alpha subunit) or CREB (Silva)

Disrupts hippocampal LTP and spatial learning

Impact of knocking out the NR1 subunit of the NMDA receptor (Tsien)

Mutation was not expressed till 3 wks after birth

Disrupted spatial learning

A conditional knockout for CaMKII

Controlled by the tetO promoter & tTA

Disrupted LTP and spatial learning

Expression of the mutation could be blocked with deoxycycline

Restored LTP and spatial learning

Making a smarter mouse: Doogie

Created mice that made the NR2B subunit of the NMDA receptor into adulthood

Exhibited enhanced LTP and learning