Synapse

Synapse

• Communication between neurons (or astrocytes) by electrical or chemical signaling
• Presynaptic neuron: axon terminal (or also dendrite or soma)
• Post synaptic neron: dendritic spines
• On average, each of the $10^{11}$ neurons in the human brain receives and makes ~ 10,000 synaptic contacts

Synapse & Dendrite

A. Pyramidal cells in CA3 region of the hippocampus from synapses on the dendrites of CA1 cells in the stratum radiatum B. The dendrites of pyramidal cells in the CA1 region of the hippocampus bear a variety of spines

Synapse & Astrocyte

Glia - more than just brain glue

Astrocytes also exchange infromation with the synaptic neurons, responding to synaptic activity and regulating neurotransmission

Synaptogenesis

• Calcium signaling (CREST, CaMKs, MAPK)
• Neurotrophic factors (BDNF)
• Regulatory proteins (Notch, Wnt, Sema3A, Slit1, Rho GTPase) and Transcription factors

Synaptic plasticity

• Synaptic transmission: Electrical (rapid) or chemical

• Synaptic plasticity

  Functional and structural changes of synapses and neurons in response to increase or decrease in their activity.

  Neurochemical foundations of learning or memory.

• Long-term potentiation (LTP)

• Long-term depression (LTD)

  Two major forms of long-lasting synaptic plasticity. A long-lasting increase in synaptic strength, respectively

Long-Term Potentiation

• A long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously

• Classical NMDA-LTP

  Calcium influx through NMDA receptors

  Activation of $Ca^{2+}$-dependent kinase

  (PKC, $\rm{Ca}$/Calmodulin kinase, tyrosine kinase)

  Inducing functional and structural change of synapse

• Early phase

  Presynaptic receptor sensitivity $\uparrow$

  Possynaptic transmitter release $\uparrow$

• Late phase

  Adenylyl cyclase $\uparrow$

  cAMP - PKA - MAPK - CREB signaling pathway

  mRNA, protein synthesis

  Formation of new synapse

Long-term Depression

• selectively weaken specific synapses in order to make constructive use of synaptic strengthening caused by LTP

• if allowed to continue increasing in strength, synapses would ultimately reach a ceiling level of efficiency, which would inhibit the encoding of new information

• LTD and LTP coincide with metaplasticity and synaptic scaling to maintain proper neuronal network function.

• Why

Neurovascular unit

• Neuron
• Astrocyte
• Vascular endothelial cell
• Vascular smooth muscle cell
• Pericyte

Synaptic degeneration

• Alzheimer’s disease
  • Hippocampus, entorhinal cortex
  • Amyloid toxicity
  • Development of drugs enhancing synaptogenesis
• Stroke
  • Loss of dendritic spines
  • Gradual improvement of higher cortical functions after stroke: cortical plasticity
• Depression
  • Decreased synaptic plasticity, reversed by antidepressant

Adult Neurogenesis

• Generation of neurons from neural precursor cells

• Immature precursor cell, Microenvironment

• Two neurogenic regions in adult mammalianbrain

  • Subgranular layer (SGL)
  • Subventricular zone (SVZ)

Neurogenesis: Adult vs fetus