3.1 GABAergic inhibitory function

GABA¶

Glutamic Acid Decarboxylase, GAD 是一种重要的酶，催化谷氨酸转化为GABA
GABA get into vesicle via GABA transporter, VGAT
GABA released to clef
GABAergic Synapses的分布：
- all excitatory synapses on spines
- but inhibitory synapses on spines, dendritic shafts and soma (even on axon)

GABA_A receptor¶

几个本课重要的离子通道
- $Na+$-K+ ATPase：将3个$Na+$泵出细胞外，同时将2个K+泵入细胞内
- KCC2：K+-Cl+公允题
- GABA_A Receptor
Concept of reversal potential:反转电位是指离子通道开放时，离子净流动方向改变的膜电位值
- Three steps of reversal potential
  - Leaving: negative charge repels negative ions: more ions leave than enter
  - Balance: negative charge balances the concentration gradient
  - Entering: negative charge too small to overcome the concentration gradient
Inhibitory postsynaptic potential (IPSP)
- 表现为：hyperpolarization
- 通过voltage clamp 测量
Inhibitory postsynaptic current (IPSC)
- GABA等抑制性神经递质激活Cl离子通道时候，产生的Cl内流电压等
- Current clamp测量

GABA_B receptor¶

A kind of G_linked GCPRs
can cause hyperpolarization, and slower IPSP than GABA_A
the beta and gamma of GABA_B receptor can cause the open of inward rectifying potassium channel, and thus K+ move outwards

¶

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和inhibition类似，但是表现形式是分流的形式
从直觉上来说，GABA的开放同时促进了正电荷向外
When postsynaptic receptors area activated, membrane conductance increases
This incraese in conductance reduces membrane resistance
分流抑制，表现为local drop in membrane resistance or membrane hyperpolarization

Model of GABAergic Neurons¶

Principal cells(black): main output of a brain area
- including in striatum and cerebellum
Interneurons(red): connect between cells in the same area

Forms of inhibition¶

- Feedforward - Information --> inhibitory cell - At the same time: information --> postsynaptic targets - soon: inhibitory cell --> postsynaptic - Feedback - Postsynaptic targets --> inhibitory cell --> postsynaptic targets - 这样的抑制性神经元有利于防止过度兴奋，维持网络稳定 - Tonic inhibition - 持续的抑制，这种抑制通常通过细胞外GABA（γ-氨基丁酸）作用于高亲和力的extrasynaptic GABAA受体亚型实现 - Lateral inhibition - 同一个population中，活跃的神经元抑制其邻近神经元，增强对比度并提高信号的空间或时间分辨率