Lecture 11: Synaptic plasticity

Question 1

Define PLASTICITY:

Dunlop, TINS 2008

Answer 1

“Plasticity is the ability of NEURONS TO REARRANGE THEIR ANATOMICAL AND FUNCTIONAL CONNECTIVITY in RESPONSE to ENVIRONMENTAL INPUT, thereby achieving NEW or MODIFIED OUTPUTS, NAMELY BEHAVIOURS.

DEVELOPMENTAL plasticity has long been recognised and plasticity in normal adults is now well
established, being the foundation of memory, learning and acquisition of new behaviours.

FUNCTIONAL plasticity includes changes in neuronal excitability and inhibition, conduction velocity and synaptic
efficacy.” - Dunlop, TINS, 2008

Question 2

Definition of PLASTICITY BY Dunlop, TINS, 2008 OMITS WHAT…?

Answer 2

This definition omits GLIA which also undergo functional and structural plasticity

Question 3

Synaptic plasticity: pre vs post synapse

Answer 3

1. action potential
2. Calcium influx
3. Vesicles bind to membrane and release neurotransmitters
4. Neurotransmitter/Ligands bind to receptors.
   ION CHANNEL OPENS
5. POST synaptic potential

Question 4

Define Plasticity (Hebbian)

Answer 4

‘NEURONS THAT FIRE TOGETHER, WIRE TOGETHER’

When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased. - DONALD HEBB 1949

Question 5

Hebbian Plasticity KEY FEATURES = 4

Answer 5

1. TIMING of neural activity is CRUCIAL for strengthening synaptic connections.
2. When two neurons FIRE SIMULTANEOUSLY, or nearly simultaneously, the connection between them is STRENGTHENED.
3. This results in increased SYNAPTIC STRENGTH and EFFICACY.
4. Hebbian plasticity is key for LEARNING, MEMORY, and the ADAPTATION of neural circuits based on experience.

Question 6

Implications of Hebbian Plasticity: 2

Answer 6

HIGH FREQUENCY synaptic activity leads to STRONGER SYNAPSES.

LOW FREQUENCY synaptic activity leads to WEAKER SYNAPSES.

Question 7

Measuring synaptic plasticity with electrophysiology: 2

Answer 7

1. Patch clamp electrophysiology
2. Local field potentials

Question 8

what is Patch-Clamp Electrophysiology: 3

Change in Amplitude of the Postsynaptic Potential: 3

Answer 8

1. INJECT CURRENT into the PRESYNAPTIC NEURON to INDUCE AN ACTION POTENTIAL (AP).
2. RECORD the size of the POSTSYNAPTIC POTENTIAL.
   Local Field Potentials:
3. ## SINGLE CELL RESOLUTIONChange in Amplitude of the Postsynaptic Potential

4.Used to measure ‘SYNAPSE STRENGTH’:

5. INCREASE = FACILITATION/POTENTIATION
6. DECREASE = SUPPRESSION/DEPRESSION

Question 9

What is Local Field Potentials: 3

Change in Amplitude and Slope of the Field Potential: 3

Answer 9

1. Use a STIMULATING ELECTRODE to ACTIVATE PRESYNAPTIC INPUTS.
2. RECORD the FIELD POTENTIAL around the POSTSYNAPTIC NEURONS.
3. NETWORK RESOLUTION (e.g., CA3 and CA1 regions).

——————————————Change in Amplitude and Slope of the Field Potential:

4. Used to measure CHANGE IN SYNAPSE STRENGTH:
5. INCREASE = FACILITATION/POTENTIATION
6. DECREASE = SUPPRESSION/DEPRESSION

Question 10

Synaptic Plasticity: Time Scales = 7

Answer 10

1. Changes to SYNAPTIC PLASTICITY can last from MILLISECONDS to HOURS and DAYS.
2. Changes to synapses that last MILLISECONDS to MINUTES are termed SHORT-TERM PLASTICITY:
   …3. ‘SHORT-TERM POTENTIATION’
   …4.’SHORT-TERM DEPRESSION’
3. Changes to synapses that last >30 MINUTES are termed LONG-TERM PLASTICITY:
   …6. ‘LONG-TERM POTENTIATION’
   …7. ‘LONG-TERM DEPRESSION’

Question 11

Discovery of Synaptic Plasticity: Long-Term Potentiation (LTP) = 5

Answer 11

1. First described in 1973 by BLISS AND LOMO.
2. Used FIELD RECORDINGS in the RABBIT HIPPOCAMPUS.
3. HIGH FREQUENCY STIMULATION of presynaptic inputs led to an INCREASE in the AMPLITUDE of the field potential at the postsynaptic region.
4. High-frequency stimulation of presynaptic inputs led to a LONG-LASTING POTENTIATION of the postsynaptic field potential.
5. LTP could be further increased with additional bouts of stimulation and eventually SATURATED.

Question 12

Long-Term Depression (LTD) = 3

Answer 12

1. First described in 1977.
2. Used FIELD RECORDINGS in the RABBIT HIPPOCAMPUS.
3. LOW FREQUENCY STIMULATION of presynaptic inputs led to a LONG-LASTING DEPRESSION of the postsynaptic field potential.

Question 13

Synaptic Plasticity: AMPA and NMDA Receptors = 4

Answer 13

1. NMDA RECEPTORS play a LARGE ROLE in the INDUCTION of synaptic plasticity.
2. NMDA RECEPTOR BLOCKERS prevent synaptic plasticity.
3. Synaptic plasticity is controlled by the NUMBER/DENSITY of AMPA RECEPTORS at the synapse.
4. ADDING OR REMOVING AMPA RECEPTORS to the synapse is a process that follows the INDUCTION of synaptic plasticity.

Question 14

Induction of Plasticity to Expression of Plasticity: 5

Answer 14

1. Induction of Plasticity:
   SYNAPTIC ACTIVITY leads to changes in the POSTSYNAPTIC DENSITY (PSD) and Ca²⁺ influx.
2. PROTEIN PHOSPHORYLATION
   – Activation of kinases leading to phosphorylation of various proteins.
3. AMPAR PROPERTIES AND TRAFFICKING
   – Changes in the properties and movement of AMPA RECEPTORS at the synapse.
4. CYTOSKELETAL REORGANISATION
   – Reorganization of the CYTOSKELETON to support changes in synaptic structure.
5. LOCAL PROTEIN SYNTHESIS
   – Synthesis of new proteins at the SYNAPSE to support plastic changes.
   Expression of Plasticity:
6. LONG-TERM CHANGES in synaptic strength, including LONG-TERM POTENTIATION (LTP) and LONG-TERM DEPRESSION (LTD).

Question 15

Cortical Ensembles: Hebbian Plasticity = 4

Answer 15

1. DONALD HEBB’S theory, “CELLS THAT FIRE TOGETHER WIRE TOGETHER,” has inspired research on SYNAPTIC PLASTICITY for approximately 70 YEARS.
2. NEURONAL ENSEMBLES are COACTIVE GROUPS of neurons that may represent the BUILDING BLOCKS of neural circuits.
3. Neuronal ensembles are COMMON in SENSORY and MOTOR CIRCUITS, where SENSORY INPUTS or MOTOR BEHAVIOURS form groups of cells that represent sensory or motor information in the brain.
4. NEURONAL ENSEMBLES are thought to arise from HEBBIAN PLASTICITY, where the CONNECTIVITY between coactive neurons becomes STRENGTHENED.

Question 16

Cortical Ensembles: Hebbian Plasticity… EXPERIMENT

Answer 16

STRONG EXPERIMENTAL EVIDENCE in favour of Hebbian plasticity comes from an OPTOGENETIC EXPERIMENT conducted in 2016.

Question 17

understanding Anti-Hebbian Plasticity = 2

Answer 17

1. HEBBIAN THEORY predicts that if one cell directly causes another to spike, the synapse between them will be POTENTIATED.
2. ANTI-HEBBIAN PLASTICITY occurs in instances where a PRE-SYNAPTIC NEURON causes the POST-SYNAPTIC NEURON to spike, but the synapse between them is DEPRESSED.

Question 18

Hebbian vs Anti-Hebbian

Answer 18

% change in synapse strength

Synchronous spiking between neurons

DIAGRAM ON SLIDE 18

Question 19

What is STDP?

Answer 19

STDP is a COMPLEX PHENOMENON as the rules for STDP vary with SYNAPSE LOCATION on the DENDRITES.

Spike Timing Dependent Plasticity (STDP)

Question 20

Spike Timing Dependent Plasticity (STDP) IMPORTANAT FEATURE?

Answer 20

TIMING of pre and postsynaptic firing is crucial for SYNAPTIC PLASTICITY

Question 21

Spike Timing Dependent Plasticity (STDP)

POSSIBILITIES = 3

Answer 21

1. PRE-SYNAPSE SPIKES before the POST-SYNAPSE:
   — Typically leads to LONG-TERM POTENTIATION (LTP).
2. PRE and POST-SYNAPSE SPIKE at the same time:
   — Can lead to NO SIGNIFICANT CHANGE or MILD PLASTICITY.
3. POST-SYNAPSE SPIKES before the PRE-SYNAPSE:
   — Typically leads to LONG-TERM DEPRESSION (LTD).

Question 22

Understanding Synaptic Weight Scaling = 4

Answer 22

1. For NORMAL BRAIN FUNCTION, SYNAPTIC PLASTICITY must be BALANCED.
2. WEIGHTS/STRENGTHS of synapses must be DYNAMIC and able to SWITCH between LONG-TERM POTENTIATION (LTP) and LONG-TERM DEPRESSION (LTD) (and vice versa) as needed.
3. The BIENSTOCK, COOPER, AND MUNRO THEORY (1982) describes a concept of how synapses SCALE THE THRESHOLDS for LTP and LTD to ADJUST THEIR STRENGTHS.
4. The theory suggests that the THRESHOLD FOR SYNAPTIC PLASTICITY SLIDES depending on the PREVIOUS ACTIVITY of the synapse.

Question 23

What is the role of metaplasticity in safeguarding against the saturation of synaptic plasticity? =

Answer 23

1. SYNAPTIC PLASTICITY is crucial for many functions, requiring SAFEGUARDS to prevent:

…2. SATURATION of synaptic plasticity (i.e., to allow for more LTP/LTD).
…3. EXCITOTOXICITY.

4. METAPLASTICITY is essentially the PLASTICITY OF SYNAPTIC PLASTICITY, with “META” reflecting the higher-order nature of this plasticity.
5. METAPLASTICITY occurs through PHYSIOLOGICAL or BIOCHEMICAL CHANGES to the neuron or synapse that ALTERS its ability to generate synaptic plasticity.

Question 24

How do metaplasticity mechanisms overlap with conventional synaptic plasticity mechanisms,

and what role does synaptic plasticity play in inducing metaplasticity?

Answer 24

1. METAPLASTICITY MECHANISMS overlap with conventional SYNAPTIC PLASTICITY MECHANISMS, making the distinction DIFFICULT.
2. SYNAPTIC PLASTICITY itself can INDUCE METAPLASTICITY

Question 25

Metaplasticity process: 4

Answer 25

1. PRIMING ACTIVITY: Includes neurotransmitters, paracrine signals, hormones, etc.
2. METAPLASTICITY: Can occur over MINUTES TO DAYS.
3. HFS/LFS LEARNING: High-Frequency Stimulation (HFS) or Low-Frequency Stimulation (LFS) can influence learning processes.
4. SYNAPTIC PLASTICITY: The result of metaplasticity and learning processes, leading to changes in synaptic strength.