| Js memo | Aim to see >?% KD of SNCA |
MEDI-1341→ ↓(~50%) aSyn spreading -→ cosequence? Eg. Neuroprotection? Behavior? Aim to see >?% KD of SNCA : p-aSyn 이 주축이 되어야 하지 않나? {Lue, 2012 #1372} 에 보면 p-aSyn 이 olf bulb only stage 에선 0 인데... 우리가 할 수 있나? Methods: -Atuka: p-aSy 확실히 생기는데, SZ 의 Update 요청하자. - patient postmortem: paper 더 찾s 아보자. -rodent: PFF model 로 가능한가? 大 characterisation 한 논문을 찾아보자 (motor symptom , 등도 같이 본 논문이 있긴 하나, 이것 neurodegeneration 정도와 같이 temporal characterisation 한 논문을 찾는 것이 도움 들 듯) - to work with Jonghun ? | ||
Electrophysiology
Anatomy of a neuron
- Myelinated section: no action potential generated due to the lack of channels on the surface of axons
- Node of ranvier: antion potential generated
- Axon terminal : action potential generated → neurotransmitter released
Methods
| protocol | Disadvantage | subtype | |||
|---|---|---|---|---|---|
| Membrane channel function | Artificial membrane-channel preparation | ||||
| Single-channel patch clamp | |||||
| Whole-cell clamp | |||||
| Cellular electrical fundtion | Voltage and Ion-Sensitive Dyes and Resins | ||||
| Isolated Neurons and Neuronal Cultures | |||||
| brain slices to study neural circuit function |
Neurons in the slide lack normal afferent inputs and efferent targets, and circulating influences like hormens or steroid, results may be heavily biased by the particular experimental conditions employed in an individual lab ( | Hippocmapl slide | LTP, postsynaptic effects of various transmitters at the membrane level, | ||
| in vivo single-cell electrophysiology to study neural circuit function |
microelectrodes in anesthetized animals, impulse activity of neurons is typically recorded extracellularly, eg) 2007 Yoshiyama (PS19 mice), j | Iontophoresis and Local Drug Application | Locus coeruleus | Opiates effect | |
| Stimulation Recording | |||||
| Local Synaptic Decoupling | |||||
| Antidromic Activation | |||||
| Single-Cell Recording in Behaving Animals | |||||
| Behavioral Electrophysiology |
extracellular recordings from a metal microelectrode held in a miniature micropositioner on the animal's head | Acute Manipulation of Specific Neurons and Neural Groups in Behaving Animals |
Resting potential (Inactive state)
- 평소엔
- All Na v-gated channels are closed
- Most K v-gated channels are closed
- Na/K pumps are open
- Na⁺/K⁺-ATPase (sodium-potassium pump) transports 2 potassium ions inside and 3 sodium ions outside at the cost of 1 ATP molecule.
- Thus , within a cell
- K high
- Na low (Na 를 계속 cell 밖으로 내보내고 있으므로)
- Thus , within a cell
- Na⁺/K⁺-ATPase (sodium-potassium pump) transports 2 potassium ions inside and 3 sodium ions outside at the cost of 1 ATP molecule.
- the respective reversal potentials (equilibrium) are +60 mV for sodium (ENa) and −80 mV for potassium (EK).
In a healthy animal cell Na⁺ permeability is about 5% of the K⁺ permeability or even less,
Thus, the cell’s resting potential will be about −73 mV.
Process
| Presynaptic cell | Synaptic cleft | Postsynaptic cell | ||
|---|---|---|---|---|
| Resting potential (Inactive state) | sodium-potassium pump 보다는 diffusion through Leakage channels 이 역할이 크고, 또 이중 K 의 (나가기만 하는) 비중이 크기 때문에 negative charge | 결국 : 평소엔 K 이 drive 하고, Action potential 은 Na 이 주로 drive 하는 것이구나. | ||
| Action potential | (Action potential 이 presynaptic terminal 에 도착하면 →) presynaptic terminal 에서 ca influx ↑ → vesicle 내의 neurotransmitter 가 released → | Neurotransmitter from presynaptic cell bind the receptors on the postsynaptic cell → ion channels open 되면서 action potential |
Synaptic input to a cell → ↑ memb potential ('depolarization') → 일부 Na channels open / ↑ Na influx, 직후 K channels open / ↑ K outflux → −55 mV (threshold potential) 도달하면 → 모든 Na channels open / ↑ Na influx → at the peak of memb potential, Na channels close while K 은 계속 나가고 있고 → {Zampese 2022} in SN DA neurons, ↑ caldium entry through Cav1 channels → calcium release from ER → mitochondrial oxidative phosphorylation) → ↓ memb potential ('repolarization') and K channels open → ↑ K outflux 시작 → (아마도 어느 ion 의 channel 이 open 되느냐에 따라)
| 근데 heart 에선 Na 후에 Ca 의 주가적인 역할이 있구나 (m contraction 하려고, & 그래서 AP 길어짐) |
Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
Process / Action potential / 직후 K channels open / 1 K outflux | 1 here represents ↑ (the OCR substitutes 1 for the up-arrow glyph); visual confirmation reads it as ↑ K outflux. | the ↑ glyph is small and partially merged with surrounding text. |
Process / Action potential / Cav1 channels | reads as Cav1 channels (Cav1, voltage-gated calcium channel type). | reads as written; Cav1 may be CaV1.x-style notation in the source. |