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. 2022 Apr 19;23(9):4508. doi: 10.3390/ijms23094508

Table 4.

Summary of the principal findings of the cited literature on α-synuclein-dependent effects on SNpc DAergic neuron functional properties.

α-Synuclein-Related Manipulation Specie Methodological
Information
Age Modified Parameters in SNpc DAergic
Neurons
Molecular Mechanisms Reference
BAC-induced overexpression of human Snca Mice
(C57/Bl6 background)
In vivo single-unit extracellular recordings in urethane-anesthetized mice 3–4 months
18–22 months
No alterations
Reduced spontaneous firing rate
[80]
Overexpression of mutated A53T-Snca Mice
(C57BL6 background)
In vivo single-unit extracellular recordings
in urethane-anesthetized mice
3–4 months
7–10 months
  • -

    Increased spontaneous firing;

  • -

    Reduced CV-ISIs;

  • -

    Increased spontaneous firing frequency;

  • -

    Increased action potential (AP) repolarization phase.

Age-dependent impairment of voltage-activated K+ channels due to redox species [82]
Spontaneous overexpression of α-syn Rat In vivo single-unit extracellular recordings
in urethane-anesthetized mice
21–30 days
  • -

    No alterations in spontaneous firing;

  • -

    No alterations in evoked excitability;

  • -

    Normal D2-activated currents;

  • -

    Normal GABAB-activated currents;

  • -

    Reduced Ih.

[8]
BAC-induced overexpression of human Snca Rat (backgroud SD) Ex vivo patch-clamp recordings in horizontal acute midbrain slices 5 months Decrease in spontaneous and evoked firing; increase in CV Increase of IAHP [86]
Intrastriatal injection of α-syn-PFF Wistar Rat Ex vivo patch-clamp recordings in horizontal acute midbrain slices from 4–6 months-old rats subjected to in vivo intrastriatal α-syn-PFF injections (6 or 12 weeks before recordings) 6 weeks after α-syn-PFF injection
  • -

    Increased frequency of spontaneous firing;

  • -

    Increased intrinsic excitability;

  • -

    Normal Ih;

  • -

    Normal D2-activated K+ currents.

[87]
12 weeks after α-syn-PFF injection
  • -

    Increased frequency of spontaneous firing;

  • -

    Increased intrinsic excitability;

  • -

    Normal Ih;

  • -

    Normal D2-activated K+ currents.

Acute injection of α-syn aggregates (oligomers and small fibrils) in single DAergic neurons C57/BL6 mice Ex vivo patch-clamp recordings in coronal acute midbrain slices 2–3 weeks
  • -

    Reduction in Rm;

  • -

    Reduced spontaneous firing;

  • -

    Reduced excitability.

α-syn-induced activation of KATP [89]