HUF 2-42 Synaptic integration, neural circuits and plasticity

Question 1

Generation of post-synaptic potentials

Answer 1

• EPSP: Na+ influx
• IPSP: K+ efflux
• Cl-: eqm. potential equal to or more -ve. than RMP
  => IPSP or shunting inhibition
  (Cl- channel opens => ↑ postsynaptic resistance)

Question 2

Spatiotemporal summation of synaptic potentials

Answer 2

• Real-time integration of all synaptic inputs to decide timing of AP
• Dendritic spines: major sites of synaptic inputs
• Aberrations in dendritic spines structure and functions
  => brain disorders e.g. dementia in Alzheimer’s disease

Question 3

Microcircuits

Answer 3

• Building blocks for complex neuronal circuits

1. Feedforward excitation
2. Feedforward inhibition
3. Convergence / Divergence
4. Lateral inhibition
5. Feedback / Recurrent inhibition
6. Feedback / Recurrent excitation

Question 4

Feedforward excitation / inhibition

Answer 4

Stretch reflex

• maintain ms. length
• sensory neuron synaptically connected with motor neuron
• feedforward excitation to flexor
• feedforward inhibition to extensor

Question 5

Convergence / Divergence

Answer 5

• many-to-1 vs. 1-to-many

- integrate functions of multiple sensory receptors and multiple ms.

Question 6

Lateral inhibition

Answer 6

• enhance perception of contrast
• enable visual system to detect contours more easily (↑ signal-to-noise ratio)
• not limited to visual functions

Question 7

Feedback inhibition

Answer 7

• prevents over-excitation of neuron
• allows generation of rhythmic activities
• reciprocal inhibition (e.g. walking)

Question 8

Neuroplasticity

Answer 8

1. Brain growth and development
2. Regain functionality
3. Learning and memory

• Changes in synaptic strength (esp. long term)
  => develop, learn, adapt
• Aberrant synaptic plasticity
  => brain disorders (e.g. chronic pain, OCD)
• Intense activities (i.e. use-dependent)
  => ↑ connection strength
  => bigger EPSP amplitude
  => Short-term potentiation (transient) OR LTP

Question 9

Long term potentiation (LTP)

Answer 9

• Early phase: protein synthesis-independent
  => short term memory
• Late phase: protein synthesis-dependent
  => long term memory
• Bidirectional change under stimulation:
  high-freq. (50-100Hz) => LTP
  low-freq. (1-3 Hz) => LTD (long term depression)

Question 10

Studying LTP in hippocampus

Answer 10

• Field potentials: reflect synaptic activity of thousands of neurons
• Bigger the amplitude, stronger the connection
• High-freq. stimulation to incoming pathways
  => ↑ amplitude of field EPSP (long-lasting: > 1 hr)

Question 11

Mechanism of LTP

Answer 11

- Intense presynaptic activity
=> ↑ glutamate release
=> bind to AMPA receptors
=> depolarisation (Na+ influx)
=> unblocking of NMDA receptor channels (Mg2+)
=> Ca2+ influx
=> LTP induction (↑ synaptic strength)

• Conditional deletion of NMDA receptor in CA1 => X LTP
• Smart mice: genetically engineered with extra copies of NMDA receptor genes

Question 12

Role of AMPA receptors in synaptic plasticity

Answer 12

AMPA receptors:

• upon GLU binding => Na+ influx
• dynamic eqm. between cell surface and intracellular recycling vesicles
• High-freq stimulation
  => rapid and big rise in Ca2+
  => phosphorylation of AMPA receptor subunits
  => stabilise AMPA receptors at postsynaptic membrane (and more are inserted)
  => LTP

- Low-freq stimulation
=> small and slow Ca2+ rise
=> dephosphorylation of AMPA receptor subunit
=> endocytosis of AMPA receptors
=> less responsive to GLU
=> LTD