IPSP

抑制性シナプス後電位

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/09/02 21:00:04」(JST)

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シナプス（Synapse）は、神経細胞間あるいは筋繊維（筋線維）、神経細胞と他種細胞間に形成される、シグナル伝達などの神経活動に関わる接合部位とその構造である。化学シナプス（小胞シナプス）と電気シナプス（無小胞シナプス）、および両者が混在する混合シナプスに分類される。シグナルを伝える方の細胞をシナプス前細胞、伝えられる方の細胞をシナプス後細胞という。

神経細胞の構造図 en:Dendrites=樹状突起、en:Rough ER (en:Nissl body)=粗面小胞体（ニッスル小体）、en:Polyribosomes=ポリリボソーム、en:Ribosomes=リボソーム、en:Golgi apparatus=ゴルジ体、en:Nucleus=細胞核、en:Nucleolus=核小体、en:Membrane=膜、en:Microtubule=微小管、en:Mitochondrion=ミトコンドリア、en:Smooth ER=滑面小胞体、en:Synapse (Axodendritic)=シナプス（軸索樹状突起） en:Synapse=シナプス、 en:Microtubule en:Neurofibrils=微小管ニューロフィラメント、en:Neurotransmitter=神経伝達物質、en:Receptor=受容体、 en:Synaptic vesicles=シナプス小胞、en:Synaptic cleft=シナプス間隙、 en:Axon terminal=軸索末端、en:Node of Ranvier =ランヴィエの絞輪 、en:Myelin Sheath(en:Schwann cell)=ミエリン鞘（シュワン細胞）、en:Axon hillock=軸索小丘、 en:Nucleus (en:Schwann cell)=細胞核（シュワン細胞）、en:Microfilament=マイクロフィラメント、en:Axon=軸索

化学シナプス

シナプス前細胞(A)からシナプス後細胞(B)への化学シナプスを経由した神経伝達の様子 (1)ミトコンドリア、(2)神経伝達物質が詰まったシナプス小胞、(3)自己受容体、(4)シナプス間隙を拡散する神経伝達物質、(5)後シナプス細胞の受容体、(6)前シナプス細胞のカルシウムイオンチャネル、(7)シナプス小胞の開口放出、(8)神経伝達物質の能動的再吸収

化学シナプスとは、細胞間に神経伝達物質が放出され、それが受容体に結合することによって細胞間の情報伝達が行われるシナプスのことを指す。化学シナプスは電気シナプスより広範に見られ、一般にシナプスとだけ言われるときはこちらを指すことが多い。

構造と機序

化学シナプスの基本的構造は、神経細胞の軸索の先端が他の細胞（神経細胞の樹状突起や筋線維）と20nm程度の隙間（シナプス間隙）を空けて、シナプス接着分子によって細胞接着している状態である。シナプス間隙は模式図では強調されて大きな隙間をあけて描かれることが多いが、実際にはかなりべったりと接合している。

情報伝達は一方向に行われ、興奮がシナプスに達するとシナプス小胞が細胞膜に融合しシナプス間隙に神経伝達物質が放出される。そして拡散した神経伝達物質がシナプス後細胞に存在する受容体に結合することで刺激が伝達されて行く。

化学シナプスにおける典型的な情報伝達機序は以下のように進む。

1. 前シナプス細胞の軸索を活動電位が伝わり、末端にある膨らみであるシナプス小頭に到達する。
2. 活動電位によりシナプス小頭の膜上に位置する電位依存性カルシウムイオンチャネルが開く。
3. するとカルシウムイオンがシナプス内に流入し、シナプス小胞が細胞膜に接して神経伝達物質が細胞外に開口放出される。
4. 神経伝達物質はシナプス間隙を拡散し、後シナプス細胞の細胞膜上に分布する神経伝達物質受容体に結合する。
5. 後シナプス細胞のイオンチャネルが開き、細胞膜内外の電位差が変化する。

分類

化学シナプスは、興奮性シナプス、抑制性シナプス（シナプス後抑制性とも呼ばれる）、シナプス前抑制性の3つに分けられる。

• 興奮性シナプスは信号を受け取ると、興奮性シナプス後電位（EPSP; Excitatory PostSynaptic Potential）という信号を発生させる。EPSPは神経細胞の分極状態が崩れる電位となるため、脱分極と呼ばれる。
• 抑制性シナプスは信号を受け取ると、抑制性シナプス後電位（IPSP; Inhibitory PostSynaptic Potential）という信号を発生させる。IPSPは神経細胞の分極状態が強化される電位となるため、過分極と呼ばれる。
• シナプス前抑制性は、興奮性シナプスが起こす興奮性シナプス後電位（EPSP）を減少させる働きを持つ。

可塑性

シナプスの活動状態などによってシナプスの伝達効率が変化するシナプス可塑性は、記憶や学習に重要な役割を持つと考えられている。

シナプス前細胞とシナプス後細胞がともに高頻度で連続発火すると、持続的なEPSPによりシナプスの伝達効率が増加する。これを長期増強（LTP; Long Term Potentiation）という。また、低頻度の発火や、抑制性シナプス後細胞の連続発火によるIPSPの持続によって、シナプスの伝達効率が低下する現象を長期抑圧（LTD; Long Term Depression）という。近年では、シナプス前細胞とシナプス後細胞の発火時間差のみによっても結合強度に変化が見られることが分かっている。これをスパイクタイミング依存シナプス可塑性（STDP; Spike Timing Dependent Plasticity）という。

また、一旦LTPやLTDを起こしたシナプスに対して適切な刺激を与えると、そのLTPやLTDが消失する事も知られており、それぞれ脱増強 (Depotentiation)、脱抑圧 (Dedepression) などと呼ばれる。

電気シナプス

電気シナプス（ギャップ結合）の模式図

電気シナプスとは、細胞間がイオンなどを通過させる分子で接着され、細胞間に直接イオン電流が流れることによって細胞間のシグナル伝達が行われるシナプスのことを指す。網膜の神経細胞間や心筋の筋繊維間などで広範に見られる。 化学シナプスのように方向づけられた伝達はできないが、それよりも高速な伝達が行われ、多くの細胞が協調して動作する現象を引き起こす。

電気シナプスは無脊椎動物の神経系では一般的にみられるが、長らく脊椎動物の中枢神経系では見出されておらず、脊椎動物の脳での神経伝達は化学シナプスのみによるものと考えられていた。 後になって海馬や大脳皮質の抑制性介在神経細胞の樹状突起間で発見され、重要な伝達手段となっていることが見出された。

構造と機序

電気シナプスは一般に、コネクソンというタンパク質6量体が2つの細胞の細胞膜を貫通し、ギャップ結合と呼ばれる細胞間結合を形成している構造を持つ。コネクソンはコネキシンというタンパク質が六角形に配列した6量体構造で、中央に小孔が存在する。この小孔はカルシウムイオン濃度によってコネクソンが変形することで開閉する。小孔が開いているときには分子量が1000程度以下の分子を通過させ、濃度勾配圧などによって拡散する。 化学シナプスが数十 nm の間隔を持つのに対して、電気シナプスではコネクソンが両細胞膜の間隔を数 nm まで接近させており、極めて近接している。

形成

発生過程でのシナプスの形成は、伸長する軸索の先端に存在する成長円錐が標的に到達した時に開始する（軸索誘導、シナプス形成、神経回路形成）。

分布等

神経筋接合部 (1)運動ニューロンの軸索、(2)神経筋接合部、(3)筋線維、(4)筋原線維

神経筋接合部の拡大図 (1)神経終末と神経終末球、(2)筋形質膜、(3)アセチルコリンを含んだシナプス小胞、(4)アセチルコリン受容体、(5)ミトコンドリア。

神経終末の末端（神経終末球）に神経インパルスが到達すると、神経伝達物質であるアセチルコリンが、筋形質膜と神経終末球の間に広がるシナプス間隙に放出される。筋形質膜の凹凸部を運動終板と呼ぶ。運動終板上にはアセチルコリン受容体が位置し、アセチルコリンを受け取ると、ナトリウムイオンチャネルが開き、ナトリウムイオンが流れ込む。すると筋活動電位が発生し、筋肉が収縮する。アセチルコリンはアセチルコリンエステラーゼによって急速に分解される。

関連項目

• 神経科学
• 神経解剖学
• ニューラルネットワーク
• ヘッブの法則

外部リンク

• シナプス - 脳科学辞典
• シナプス小胞 - 脳科学辞典
• 神経筋接合部 - 脳科学辞典　運動神経と筋肉との間のシナプスについての解説。
• 放出可能プール - 脳科学辞典　神経伝達に関わるシナプス顆粒のうち、即座に放出できるプールについての解説。
• 遅いシナプス後電位 - 脳科学辞典　神経伝達のうち代謝型受容体に担われるおそい成分についての解説。
• FM1-43 - 脳科学辞典　シナプス顆粒の放出を可視化する色素であるFM1-43についての解説。
• シナプス前終末 - 脳科学辞典　

wiki en

[Wiki en表示]

An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a postsynaptic neuron less likely to generate an action potential. The opposite of an inhibitory postsynaptic potential is an excitatory postsynaptic potential (EPSP), which is a synaptic potential that makes a postsynaptic neuron more likely to generate an action potential. They can take place at all chemical synapses, which use the secretion of neurotransmitters to create cell to cell signalling. Inhibitory presynaptic neurons release neurotransmitters that then bind to the postsynaptic receptors; this induces a postsynaptic conductance change as ion channels open or close. An electric current that changes the postsynaptic membrane potential to create a more negative postsynaptic potential is generated. Depolarization can also occur due to an IPSP if the reverse potential is between the resting threshold and the action potential threshold. Another way to look at inhibitory postsynaptic potentials is that they are also a chloride conductance change in the neuronal cell because it decreases the driving force.Microelectrodes can be used to measure postsynaptic potentials at either excitatory or inhibitory synapses.

In general, a postsynaptic potential is dependent on the type and combination of receptor channel, reverse potential of the postsynaptic potential, action potential threshold voltage, ionic permeability of the ion channel, as well as the concentrations of the ions in and out of the cell; this determines if it is excitatory or inhibitory. IPSPs always want to keep the membrane potential more negative than the action potential threshold and can be seen as a “transient hyperpolarization”. EPSPs and IPSPs compete with each other at numerous synapses of a neuron; this determines whether or not the action potential at the presynaptic terminal will regenerate at the postsynaptic membrane. Some common neurotransmitters involved in IPSPs are GABA and glycine.

Flowchart describing how an inhibitory postsynaptic potential works from neurotransmitter release to summation

Components

Types

This system IPSPs can be temporally summed with subthreshold or suprathreshold EPSPs to reduce the amplitude of the resultant postsynaptic potential. Equivalent EPSPs (positive) and IPSPs (negative) can cancel each other out when summed. The balance between EPSPs and IPSPs is very important in the integration of electrical information produced by inhibitory and excitatory synapses.

Graph displaying an EPSP, an IPSP, and the summation of an EPSP and an IPSP. When the two are summed together the potential is still below the action potential threshold.

Factors

The size of the neuron can also affect the inhibitory postsynaptic potential. Simple temporal summation of postsynaptic potentials occurs in smaller neurons, whereas in larger neurons larger numbers of synapses and ionotropic receptors as well as a longer distance from the synapse to the soma enables the prolongation of interactions between neurons.

Inhibitory Molecules

GABA is a very common neurotransmitter used in IPSPs in the adult mammalian brain and retina. GABA receptors are pentamers most commonly composed of three different subunits (α, β, γ), although several other subunits (δ,ε, θ, π, ρ) and conformations exist. The open channels are selectively permeable to chloride or potassium ions (depending on the type of receptor) and allow these ions to pass through the membrane. If the electrochemical potential of the ion is more negative than that of the action potential threshold then the resultant conductance change that occurs due to the binding of GABA to its receptors keeps the postsynaptic potential more negative than the threshold and decreases the probability of the postsynaptic neuron completing an action potential. Glycine molecules and receptors work much in the same way in the spinal cord, brain, and retina.

Inhibitory Receptors

There are two types of inhibitory receptors:

Ionotropic receptors

Ionotropic receptors (also known as ligand-gated ion channels) play an important role in inhibitory postsynaptic potentials. A neurotransmitter binds to the extracellular site and opens the ion channel that is made up of a membrane-spanning domain that allows ions to flow across the membrane inside the postsynaptic cell. This type of receptor produces very fast postsynaptic actions within a couple of milliseconds of the presynaptic terminal receiving an action potential. These channels influence the amplitude and time-course of postsynaptic potentials as a whole. Ionotropic GABA receptors are used in binding for various drugs such as barbiturates (Phenobarbital, pentobarbital), steroids, and picrotoxin. Benzodiazepines (Valium) bind to the α and δ subunits of GABA receptors in order to improve GABAergic signaling. Alcohol also modulates ionotropic GABA receptors.

Metabotropic receptors

Metabotropic receptors, or G-protein-coupled receptors, do not use ion channels in their structure; they, instead, consist of an extracellular domain that binds to a neurotransmitter and an intracellular domain that binds to G-protein. This begins the activation of the G-protein, which then releases itself from the receptor and interacts with ion channels and other proteins to open or close ion channels through intracellular messengers. They produce slow postsynaptic responses (from milliseconds to minutes) and can be activated in conjunction with ionotropic receptors to create both fast and slow postsynaptic potentials at one particular synapse. Metabotropic GABA receptors, heterodimers of R1 and R2 subunits, use potassium channels instead of chloride. They can also block calcium ion channels in order to hyperpolarize postsynaptic cells.

Significance

There are many applications of inhibitory postsynaptic potentials to the real world. Drugs that affect the actions of the neurotransmitter can treat neurological and psychological disorders through different combinations of types of receptors, G-proteins, and ion channels in postsynaptic neurons.

For example, studies researching opioid receptor-mediated receptor desensitizing and trafficking in the locus cereleus of the brain are being performed. When a high concentration of agonist is applied for an extended amount of time (fifteen minutes or more), hyperpolarization peaks and then decreases. This is significant because it is a prelude to tolerance; the more opioids one needs for pain the greater the tolerance of the patient. These studies are important because it helps us to learn more about how we deal with pain and our responses to various substances that help treat pain. By studying our tolerance to pain, we can develop more efficient medications for pain treatment.

In addition, research is being performed in the field of dopamine neurons in the ventral tegmental area, which deals with reward, and the substantia nigra, which is involved with movement and motivation. Metabotropic responses occur in dopamine neurons through the regulation of the excitability of cells. Opioids inhibit GABA release; this decreases the amount of inhibition and allows them to fire spontaneously. Morphine and opioids relate to inhibitory postsynaptic potentials because they induce disinhibition in dopamine neurons.

IPSPs can also be used to study the input-output characteristics of an inhibitory forebrain synapse used to further study learned behavior, to be specific song learning in birds in a study performed at the University of Washington. Poisson trains of unitary IPSPs were induced at a high frequency to reproduce postsynaptic spiking in the medial portion of the dorsalateral thalamic nucleus without any extra excitatory inputs. This shows an excess of thalamic GABAergic activation. This is important because spiking timing is needed for proper sound localization in the ascending auditory pathways. Songbirds use GABAergic calyceal synaptic terminals and a calcyx-like synapse such that each cell in the dorsalateral thalamic nucleus receives at most two axon terminals from the basal ganglia to create large postsynaptic currents.

Inhibitory postsynaptic potentials are also used to study the basal ganglia of amphibians to see how motor function is modulated through its inhibitory outputs from the striatum to the tectum and tegmentum. Visually guided behaviors may be regulated through the inhibitory striato-tegmental pathway found in amphibians in a study performed at the Baylor College of Medicine and the Chinese Academy of Sciences. The basal ganglia in amphibians is very important in receiving visual, auditory, olfactory, and mechansensory inputs; the disinhibitory striato-protecto-tectal pathway is important in prey-catching behaviors of amphibians. When the ipsilateral striatum of an adult toad was electrically stimulated, inhibitory postsynaptic potentials were induced in binocular tegmental neurons, which affects the visual system of the toad.

Studies

Inhibitory postsynaptic potentials can be inhibited themselves through a signaling process called “depolarized-induced suppression of inhibition (DSI)” in CA1 pyramidal cells and cerebral Purkinje cells. In a laboratory setting step depolarizations the soma have been used to create DSIs, but it can also be achieved through synaptically induced depolarization of the dendrites. DSIs can be blocked by ionotropic receptor calcium ion channel antagonists on the somata and proximal apical dendrites of CA1 pyramidal cells. Dendritic inhibitory postsynaptic potentials can be severely reduced by DSIs through direct depolarization.

Along these lines, inhibitory postsynaptic potentials are useful in the signaling of the olfactory bulb to the olfactory cortex. EPSPs are amplified by persistent sodium ion conductance in external tufted cells. Low-voltage activated calcium ion conductance enhances even larger EPSPs. The hyperpolarization activated nonselective cation conductance decreases EPSP summation and duration and they also change inhibitory inputs into postsynaptic excitation. IPSPs come into the picture when the tufted cells membranes are depolarized and IPSPs then cause inhibition. At resting threshold IPSPs induce action potentials. GABA is responsible for much of the work of the IPSPs in the external tufted cells.

Another interesting study of inhibitory postsynaptic potentials looks at neuronal theta rhythm oscillations that can be used to represent electrophysiological phenomena and various behaviors. Theta rhythms are found in the hippocampus and GABAergic synaptic inhibition helps to modulate them. They are dependent on IPSPs and started in either CA3 by muscarinic acetylcholine receptors and within C1 by the activation of group I metabotropic glutamate receptors. When interneurons are activated by metabotropic acetylcholine receptors in the CA1 region of rat hippocampal slices, a theta pattern of IPSPs in pyramidal cells occurs independent of the input. This research also studies DSIs, showing that DSIs interrupt metabotropic acetylcholine-initiated rhythm through the release of endocannabinoids. An endocannabinoid-dependent mechanism can disrupt theta IPSPs through action potentials delivered as a burst pattern or brief train. In addition, the activation of metabotropic glutamate receptors removes any theta IPSP activity through a G-protein, calcium ion–independent pathway.

Inhibitory postsynaptic potentials have also been studied in the Purkinje cell through dendritic amplification. The study focused in on the propagation of IPSPs along dendrites and its dependency of ionotropic receptors by measuring the amplitude and time-course of the inhibitory postsynaptic potential. The results showed that both compound and unitary inhibitory postsynaptic potentials are amplified by dendritic calcium ion channels. The width of a somatic IPSP is independent of the distance between the soma and the synapse whereas the rise time increases with this distance. These IPSPs also regulate theta rhythms in pyramidal cells. On the other hand, inhibitory postsynaptic potentials are depolarizing and sometimes excitatory in immature mammalian spinal neurons because of high concentrations of intracellular chloride through ionotropic GABA or glycine chloride ion channels. These depolarizations activate voltage-dependent calcium channels. They later become hyperpolarizing as the mammal matures. To be specific, in rats, this maturation occurs during the perinatal period when brain stem projects reach the lumbar enlargement. Descending modulatory inputs are necessary for the developmental shift from depolarizing to hyperpolarizing inhibitory postsynaptic potentials. This was studied through complete spinal cord transections at birth of rats and recording IPSPs from lumbar motoneurons at the end of the first week after birth.

Glutamate, an excitatory neurotransmitter, is usually associated with excitatory postsynaptic potentials in synaptic transmission. However, a study completed at the Vollum Institute at the Oregon Health Sciences University demonstrates that glutamate can also be used to induce inhibitory postsynaptic potentials in neurons. This study explains that metabotropic glutamate receptors feature activated G proteins in dopamine neurons that induce phosphoinositide hydrolysis. The resultant products bind to inositol triphosphate (IP3) receptors through calcium ion channels. The calcium comes from stores and activate potassium conductance, which causes a pure inhibition in the dopamine cells. The changing levels of synaptically released glutamate creates an excitation through the activation of ionotropic receptors, followed by the inhibition of metabotropic glutamate receptors.

See also

• Excitatory postsynaptic potential
• GABA
• Glycine
• Nonspiking neurons
• Postsynaptic potential

References

English Journal

• VvPIP2;4N aquaporin involvement in controlling leaf hydraulic capacitance and resistance in grapevine.

• Vitali M1, Cochard H2,3, Gambino G4, Ponomarenko A2, Perrone I4, Lovisolo C5,2.
• Physiologia plantarum.Physiol Plant.2016 Nov;158(3):284-296. doi: 10.1111/ppl.12463. Epub 2016 Jun 8.
• Hydraulic capacitance (C) in a plant tissue buffers the xylem tension, storing and releasing water and has been highlighted in recent years as an important factor that affects water relations such as drought tolerance and embolism formation. Aquaporins (AQPs) are well known to control leaf hydraulic
• PMID 27137520

• Differential regulation of spontaneous and evoked inhibitory synaptic transmission in somatosensory cortex by retinoic acid.

• X Yee A1,2, Chen L3,4.
• Synapse (New York, N.Y.).Synapse.2016 Nov;70(11):445-52. doi: 10.1002/syn.21921. Epub 2016 Jul 12.
• Retinoic acid (RA), a developmental morphogen, has emerged in recent studies as a novel synaptic signaling molecule that acts in mature hippocampal neurons to modulate excitatory and inhibitory synaptic transmission in the context of homeostatic synaptic plasticity. However, it is unclear whether RA
• PMID 27348405

• Active integration of glutamatergic input to the inferior olive generates bi-directional postsynaptic potentials.

• Garden D1, Rinaldi A1, Nolan MF2.
• The Journal of physiology.J Physiol.2016 Oct 21. doi: 10.1113/JP273424. [Epub ahead of print]
• The inferior olive plays a critical role in motor coordination and learning by integrating diverse afferent signals to generate climbing fibre inputs to the cerebellar cortex. While it is well established that climbing fibre signals are important for motor coordination, the mechanisms by which neuro
• PMID 27767209

Japanese Journal

• Ethylene-di-urea (EDU), an effective phytoproctectant against O3 deleterious effects and a valuable research tool

• 農業気象 71(3), 185-195, 2015
• NAID 130005098163

• Ethylene-di-urea (EDU), an effective phytoproctectant against O3 deleterious effects and a valuable research tool

• 農業気象 advpub(0), 2015
• NAID 130005085259

• てんかんの病態生理とてんかんおよびてんかん発作の分類 (今月の特集 てんかんと臨床検査のかかわり)

• 臨床検査 58(9), 1034-1044, 2014-09
• NAID 40020190497

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★リンクテーブル★

リンク元	「抑制性シナプス後電位」「inhibitory postsynaptic potential」
関連記事	「IP」「IPSPs」

「抑制性シナプス後電位」

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英

inhibitory postsynaptic potential, IPSP

• Clチャネルの開口により過分極して生じる電位 (PT.70)

「inhibitory postsynaptic potential」

　　[★] 抑制性シナプス後電位 IPSP

「IP」

　　[★]

• inositol trisphosphate
• inorganic phosphorus 無機リン
• interpharangeal
• 間質性肺炎 interstitial pneumonitis

　

「IPSPs」

　　[★]

関

Inhibitory postsynaptic potentials