Week 7 Flashcards
(9 cards)
Long Term potentiation Properties
Temporal: Summation of inputs reaches a stimulus threshold that leads to the induction of LTP. e.g. Repetitive stimulation (HFS)
Input Specific: LTP at one synapse is not propagated to adjacent synapses (input specific).
Associative: simultaneous stimulation of a strong and weak pathway will induce LTP at both pathways. (Spatial summation)
Morris Water Maze
Rat in a tub of water with a platform somewhere to stand on
Rat with hippocampus legion doesn’t learn where platform is after 10 trials
What’s happening at synapse during this
Glutamate release onto inactive cell (membrane at resting potential) :
AMPA receptor activated to create EPSP
NMDA receptor blocked by Mg2+ ion
Depolarization from AMPA activation not sufficient to expel Mg2+
Glutamate release onto an active cell (membrane depolarized):
AMPA receptor activated
Mg2+ block on NMDA receptor relieved
Na+ through AMPA and NMDA channels
Ca2+ influx through NMDA channel
Ca2+ entry through the NMDA receptor leads to:
Activation of Calcium calmodulin-dependent protein kinase II (CaMKII) - Molecular switch which maintains increased excitability of neuron for minutes to hours
1) phosphorylates existing AMPA receptors increasing their effectiveness
2) stimulates the insertion of new AMPA receptors into the membrane
Presynaptic events in LTP:
Long term potentiation can also involve presynaptic events.
Postsynaptic neuron can feed back to presynaptic neuron by retrograde neurotransmitter - Nitric Oxide (NO)
1) Ca2+ through the NMDA channel activates Nitric oxide synthase
2) NO diffuses from site of production and activates guanylyl cyclase in the presynaptic terminal
3) Guanylyl cyclase produces the second messenger cGMP
4) Signal transduction cascade leads to increased glutamate release from the synaptic bouton
Early vs late phase LTP (short vs long term events)
Early phase LTP lasts a minute to an hour… explained by the actions of Ca2+ through the NMDA receptor and subsequent enhancement of AMPA receptor efficiency, presynaptic events etc.
Late phase LTP lasts hours, days or months… requires new protein synthesis and can involve morphological changes and the establishment of new synapses (tetanic stimulation)
Ca2+ activated signal transduction cascades:
- activate new protein synthesis
(dendritically localized mRNAs)
signal to cell body… new gene transcription
(CREB –mediated)…protein synthesis and
recruitment of new proteins to the synapse
Always an opposite - Long Term Depression
Long Term Potentiation - High frequency stimulation
Low frequency stimulation - decrease in EPSP amplitude decrease
Long Term Depression (LTD)
Same players involved:
NMDA dependent process
AMPA receptors are dephosphorylated and
removed from the membrane
(low level rises in Ca2+ activate phosphatase rather than kinase)
Tetanic stimulation is artificially high, is there a biological equivalent?
Theta rhythms: The hippocampal theta rhythm,a neural oscillation with a frequency of 4-12 Hz
Key brain signal implicated in memory, spatial navigation, and coordinating brain-wide neuronal networks, particularly during active exploration and REM sleep.
disruption in theta waves causes deficits in learning tasks that are similar to those caused by hippocampal lesions
Enhancing Memory:
Living in enriched environment improves cognition
Decreases with Age
Genetics: Increased amounts of a particular type of the NMDA receptor (NR2B receptor) leads to enhanced LTP