Neuroscience

1. Long term potentiation and
depression
Domina Petric, MD

2. Plasticity
It is capacity of the nervous system
to change.
Plasticity can be short term
(seconds to minutes) or long term
(minutes to day to life-time).

3. Plasticity occurs at:
synapses
within the
structure and
function of
neuron
within glial
cells
(astrocytes)

4. Plasticity
Plasticity affects the structure and
function of neural circuits and
systems.
Plasticity affects the organization
of functional representations
(cortical maps).

5. Plasticity is the basis of:
• memory
• acquisition of motor skills
• acquisition of cognitive skills (learning,
language...)
• adaptation and recovery from injury or
disability

6. Cellular mechanisms of
synaptic plasticity
• Neural activity triggers the
activation of postsynaptic, second
messenger systems.
• Trigger is usually an alteration in
the level of intracellular calcium in
the postsynaptic neuron.

7. Cellular mechanisms of
synaptic plasticity
Calcium-dependent second messenger
systems alter the activity of :
• protein kinases (phosphorylate
target proteins)
• phosphatases (dephosphorylate
target proteins)

8. Plasticity
Alterations in
protein
phosphorylation
mediate the early
stages of long-
term synaptic
plasticity.

9. LTP (long term potentiation)
Specificity
In order for a
pathway to be
potentiated, it
must be
active.
Associativity
If the weak pathway
is concurrently
activated with a
strong pathway then
the weak pathway is
strengthened (the
weak synapse can be
potentiated).

10. LTP and silent synapses
• Silent synapse is a synapse that might be
capable of function, but it lacks AMPA
glutamate receptors.
• In developing brain there are silent
synapses with NMDA glutamate
receptors and not enough AMPA
receptors for normal function of
synapse.

11. LTP and silent synapses
• In the presence of stimulations that can
induce LTP there is insertion of AMPA
receptors close to the NMDA receptors.
• LTP awakens silent synapse that turns
to functional synapse that contains both
AMPA glutamate and NMDA glutamate
receptors.

12. AMPA and NMDA receptors
• AMPA glutamate receptors can
respond to a milder postsynaptic
depolarisation, but NMDA glutamate
receptors respond only to significant
depolarisation, strong enough to
evacuate magnesium ions that block
the opening of the channel.

13. LTP
https://sites.google.com/site/mcauliffeneur

14. LTD (long term depression)
When there is a period of
low frequency stimulation,
there is a 50% decrease in
synaptic strength and even
more decrease during a
long period of time.

15. LTD
• When there is slower and lower level
increase in postsynaptic calcium, protein
phosphatases are activated.
• Protein phosphatases dephosphorylate
target proteins.
(In LTP higher level increase in postsynaptic
calcium activates protein kinases that
phosphorylate target proteins.)

16. LTD
Activation of protein phosphatases leads
to the internalisation of AMPA receptors
(AMPA receptors are removed).
Activation of protein kinases in LTP
leads to the mobilisation of new AMPA
receptors.

17. LTD in the cerebellum
The principal cell in the cerebellum is
the Purkinje cell.
Brittanica.com

18. LTD in the cerebellum
• Main synapse in the cerebellum is the
synapse between the parallel fiber and
Purkinje cell.
• Climbing fibres (axons) from Inferior
olivary nucleus make also a very
important and strong synaptic
connection with the dendrites of the
Purkinje cell.
The strongest known synapse in the human CNS.

19. LTD in the cerebellum
The pairing of the activity
between the climbing fiber and
the parallel fiber is what causes
the depression in the strength
of the connection between the
parallel fiber and Purkinje cell.

20. LTD in the cerebellum
• In the synapse between parallel fiber and
Purkinje cell there are AMPA glutamate
receptors and metabotropic glutamate
receptors (mGluR).
• Climbing fibers open voltage gated
calcium channels in the Purkinje cells
dendrites.

21. LTD in the cerebellum
• Because of a sudden and high-level rise of
intracellular calcium in dendrites there is
internalisation of AMPA receptors.
• In the cerebellum protein kinase C
phosphorylates target proteins that leads
to the internalisation of AMPA glutamate
receptors and LTD.

22. Role of calcium levels
In the cerebral cortex high
levels of calcium lead to long
term potentiation, BUT in
the cerebellar cortex high
levels of calcium lead to long
term depression.

23. Literature
• https://www.coursera.org/learn/
medical-neuroscience/lecture:
Leonard E. White, PhD, Duke
University
• https://sites.google.com/site/mcauliffeneur
• Brittanica.com