IPSPs/EPSPs

The EEG is produced by electrical dipoles in the outer brain cortex. The waveform is too low in frequency to be the summed result of fast action potential events. Instead, the electric signal is believed to be attributable to the aggregate of excitatory and inhibitory postsynaptic potentials (EPSPs/IPSPs). 

Fig. 8. Intracellular records from an organotypic culture of hippocampal pyramidal cells to show synaptic responses to monopolar field stimulation and the response to bath-applied met-enkephalin. Monopolar field stimulation within the culture produced in pyramidal cells an epsp-ipsp sequence. Twenty seconds before the onset of recording, 10 M met-enkephalin (A) and 10 M FK 33-824 (B) were bath-applied. The enkephalin first elicited single spikes riding on the epsp s and then caused sustained firing with bursts of activity followed by silent periods. During the silent periods, the complete blockade of ipsp s can be clearly observed. The effect of M bicuculline methochloride was tested on the same cell. Both records were taken from the same cell. Stimulation (indicated as dots) parameters were 1 Hz, 0.1 msec, 6 xA, resting membrane potential -65 mV, age of the culture 40 days (From Gahwiler, 1980.)...

An inhibitory input increases the influx of Cl to make the inside of the neuron more negative. This hyperpolarisation, the inhibitory postsynaptic potential (IPSP), takes the membrane potential further away from threshold and firing. It is the mirror-image of the EPSP and will reduce the chance of an EPSP reaching threshold voltage. 

Not all influences on, or potentials recorded from, a neuron have the same time-course as the EPSP and IPSP, which follow the rapid opening of Na+ and Cl ion charmels directly linked to NT receptors. There are also slowly developing, longer lasting and smaller non-propagated (conditioning) changes in potential most of which appear to have a biochemical intermediary in the form of G-proteins linked to the activation (Gs) or... 

Figure 1.4 Ionic basis for excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs). Resting membrane potential ( — 70 mV) is maintained by Na+ influx and K+ efflux. Varying degrees of depolarisation, shown by different sized EPSPs (a and b), are caused by increasing influx of Na. When the membrane potential moves towards threshold potential (60-65 mV) an action potential is initiated (c). The IPSPs (a b ) are produced by an influx of Cl. Coincidence of an EPSP (b) and IPSP (a ) reduces the size of the EPSP (d)...

As previously mentioned, a single action potential at a single synapse results in a graded potential only an EPSP or an IPSP. Therefore, generation of an action potential in the postsynaptic neuron requires the addition or summation of a sufficient number of excitatory inputs to depolarize this neuron to threshold. Two types of summation may occur ... 

Temporal summation occurs when multiple EPSPs (or IPSPs) produced by a single presynaptic neuron in close sequence exert their effect on membrane potential of the postsynaptic neuron. For example, an action potential in the presynaptic neuron produces an EPSP and partial depolarization of the postsynaptic neuron (see Figure 5.2). While the postsynaptic neuron is still depolarized, a second action potential in the presynaptic neuron produces another EPSP in the postsynaptic neuron that adds to the first and further depolarizes this neuron. 

Figure 5.3 Spatial summation. Multiple excitatory postsynaptic potentials (EPSPs) or inhibitory postsynaptic potentials (IPSPs) produced by many presynaptic neurons simultaneously may add together to alter the membrane potential of the postsynaptic neuron. Sufficient excitatory input (A and B) will depolarize the membrane to threshold and generate an action potential. The simultaneous arrival of excitatory and inhibitory inputs (A and C) may cancel each other out so that the membrane potential does not change.

Activation of ionotropic mechanisms creates postsynaptic potentials. An influx of cations or efflux of anions depolarizes the neuron, creating an excitatory-postsynaptic potential (EPSP). Conversely, an influx of anions or efflux of cations hyperpolarizes the neuron, creating an inhibitory-postsynaptic potential (IPSP). Postsynaptic potentials are summated both... 

When receptors are directly linked to ion channels, fast excitatory postsynaptic potentials (EPSPs) or inhibitory postsynaptic potentials (IPSPs) occur. However, it is well established that slow potential changes also occur and that such changes are due to the receptor being linked to the ion channel indirectly via a second messenger system. 

During a laboratory demonstration to depict the complexity of neurotransmission in autonomic ganglia, Professor Smith sets up an anesthetized mammalian preparation in which she is recording postsynaptic events following the electrical stimulation of preganglionic sympathetic nerves. This demonstrates a complex action potential that consists of a fast EPSP followed by a slow IPSP followed by a slow EPSP and finally by a late very slow EPSP. 

In Professor Smith s demonstration, the slow EPSP and slow IPSP can both be blocked by prior administration of... 

B. The receptor contributing to the slow EPSP is a muscarinic-cholinergic receptor and is activated by ACh. The nicotinic-cholinergic receptor mediates the fast EPSP, an a-receptor may mediate the slow IPSP, and a Pzx receptor and a (3-adrenergic receptor do not appear to be involved in the complex action potentials seen at autonomic ganglia. 

Most neurons in the CNS receive both EPSP and IPSP input. Thus, several different types of neurotransmitters may act on the same neuron, but each binds to its own specific receptor. The overall resultant action is due to the summation of the individual actions of the various neurotransmitters on the neuron. The neurotransmitters are not uniformly distributed in the CNS but are localized in specific clusters of neurons whose axons may synapse with specific regions of the brain. Many neuronal tracts thus seem to be chemically coded, and this may offer greater opportunity for selective modulation of certain neuronal pathways. 

Pitman, R. M. and Kerkut, G. A. (1970) Comparison of the actions of iontophoretically applied acetylcholine and gamma aminobutyric acid with the EPSP and IPSP in cockroach central neurones. Comp. gen. Pharmacol., 1,221-231. 

Combination of the transmitter with postjunctional receptors and production of the postjunctional potential. The released transmitter diffuses across the synaptic or junctional cleft and combines with specialized receptors on the postjunctional membrane this often results in a localized increase in the ionic permeability, or conductance, of the membrane. With certain exceptions (noted below), one of three types of permeabdity change can occur (a) a generalized increase in the permeabdity to cations (notably Na+ but occasionady Ca +), resulting in a localized depolarization of the membrane, i.e., an excitatory postsynaptic potential (EPSP) (b) a selective increase in permeabdity to anions, usually Q, resulting in stabdization or hyperpolarization of the membrane (an inhibitory postsynaptic potential or IPSP) or (c) an increased permeability to K+ (the K+ gradient is directed outward thus, hyperpolarization results, i.e., an IPSP). 

---