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Key Event Title
Generation, Amplified excitatory postsynaptic potential (EPSP)
Key Event Components
|excitatory postsynaptic potential||occurrence|
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP||Point of Contact||Author Status||OECD Status|
|Blocking iGABA receptor ion channel leading to seizures||KeyEvent||Ping Gong (send email)||Open for citation & comment||WPHA/WNT Endorsed|
Key Event Description
In neuroscience, an excitatory postsynaptic potential (EPSP) is defined as a neurotransmitter-induced postsynaptic potential change that depolarizes the cell, and hence increases the likelihood of initiating a postsynaptic action potential (Purves et al. 2001). On the contrary, an inhibitory postsynaptic potential (IPSP) decreases this likelihood. Whether a postsynaptic response is an EPSP or an IPSP depends on the type of channel that is coupled to the receptor, and on the concentration of permeant ions inside and outside the cell. In fact, the only factor that distinguishes postsynaptic excitation from inhibition is the reversal potential of the postsynaptic potential (PSP) in relation to the threshold voltage for generating action potentials in the postsynaptic cell. When an active presynaptic cell releases neurotransmitters into the synapse, some of them bind to receptors on the postsynaptic cell. Many of these receptors contain an ion channel capable of passing positively charged ions (e.g., Na+ or K+) or negatively charged ions (e.g., Cl-) either into or out of the cell. In epileptogenesis, discharges reduced GABAA receptor-mediated hyperpolarizing IPSPs by shifting their reversal potentials in a positive direction. At the same time, the amplitudes of Schaffer collateral-evoked RS-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated EPSPs and action potential-independent miniature EPSPs were enhanced, whereas N-methyl-d-aspartate receptor-mediated EPSPs remained unchanged. Together, these changes in synaptic transmission produce a sustained increase in hippocampal excitability (Lopantsev et al. 2009).
How It Is Measured or Detected
EPSPs are usually recorded by measuring electrical responses and changes in intracellular calcium concentration using intracellular electrodes (Miura et al. 1997) or recording extracellular electrical activity or potential using >20 electroencephalogram (EEG) electrodes (often in clinical settings) (Bromfield et al. 2006). Recently, voltage-sensitive dyes have been successfully used for measuring voltage responses from large neuronal populations in acute brain slice preparations (Popovic et al. 2015; Acker et al. 2016).
Domain of Applicability
Miura et al. (1997) reported supporting evidence from guinea pigs whereas Dichter and Ayala (1987) and Bromfield et al. (2006) summarized relevant studies on humans. Acker et al. (2016) perform simultaneous two-photon voltage-sensitive dye recording with two-photon glutamate uncaging in order to measure the characteristics (amplitude and duration) of uncaging-evoked EPSPs in acute mouse brain slices.
Acker CD, Hoyos E, Loew LM. (2016) EPSPs Measured in Proximal Dendritic Spines of Cortical Pyramidal Neurons. eNeuro. 3(2) ENEURO.0050-15.2016.
Bromfield EB, Cavazos JE, Sirven JI. (2006) Chapter 1, Basic Mechanisms Underlying Seizures and Epilepsy. In: An Introduction to Epilepsy [Internet]. West Hartford (CT): American Epilepsy Society; Available from: http://www.ncbi.nlm.nih.gov/books/NBK2510/.
Dichter MA, Ayala GF. (1987) Cellular mechanisms of epilepsy: A status report. Science 237:157-64.
Lopantsev V, Both M, Draguhn A. 2009. Rapid Plasticity at Inhibitory and Excitatory Synapses in the Hippocampus Induced by Ictal Epileptiform Discharges. Eur J Neurosci 29(6):1153–64.
Miura M, Yoshioka M, Miyakawa H, Kato H, Ito KI. (1997) Properties of calcium spikes revealed during GABAA receptor antagonism in hippocampal CA1 neurons from guinea pigs. J Neurophysiol. 78(5):2269-79.
Popovic MA, Carnevale N, Rozsa B, Zecevic D. (2015) Electrical behaviour of dendritic spines as revealed by voltage imaging. Nature Communications. 6:8436.
Purves D, Augustine GJ, Fitzpatrick D, Katz LC, LaMantia A-S, McNamara JO, Williams SM (Eds). 2001. Neuroscience. 2nd edition. Chapter 7. Neurotransmitter Receptors and Their Effects. Sunderland (MA): Sinauer Associates. Available from: http://www.ncbi.nlm.nih.gov/books/NBK10799/.