Synaptic current

Figure 2.12 From voltage-clamp to current-clamp micro-electrode recordings of synaptic current (/, lower trace) and synaptic potential with superimposed action potential (V, upper trace) from a neuron in an isolated rat superior cervical sympathetic ganglion following a single stimulus (S) applied to the preganglionic nerve trunk. The interval between the stimulus and the postsynaptic response includes the conduction time along the unmyelinated axons of the preganglionic nerve trunk. (SJ Marsh and DA Brown, unpublished)...

Edwards, FA, Gibb, AJ and Colquhoun, D (1992) ATP receptor mediated synaptic currents in the central nervous system. Nature 359 144-147. 

Macroscopic Kinetics Relaxations (Such as Synaptic Currents) and Noise...198... 

The ion-channel blocking mechanism has been widely tested and found to be important in both pharmacology and physiology. Examples are the block of nerve and cardiac sodium channels by local anesthetics, or block of NMDA receptor channels by Mg2+ and the anesthetic ketamine. The channel-block mechanism was first used quantitatively to describe block of the squid axon K+ current by tetraethylammonium (TEA) ions. The effects of channel blockers on synaptic potentials and synaptic currents were investigated, particularly at the neuromuscular junction, and the development of the single-channel recording technique allowed channel blockages to be observed directly for the first time. 

The assumption that (> is very small has been used when studying the effects of channel blockers on synaptic currents, as the transmitter concentration (and hencepAlB) is probably small during the decay phase of the current. During noise analysis experiments, a low agonist concentration is used so that, again, under these conditions (5 should be small. 

Hoffman, N. W., Wuarin, J. P. Dudek, F. E. (1994). Whole-cell recordings of spontaneous synaptic currents in medial preoptic neurons from rat hypothalamic shces mediation by amino acid neurotransmitters. Brain Res. 660, 349-52. 

Seizures result from excessive excitation, or from disordered inhibition of a population of neurons. Initially, a small number of neurons fire abnormally. Then normal membrane conductances and inhibitory synaptic currents break down, excitability spreads locally (focal seizure) or more widely (generalized seizure). 

Bureau, I., Dieudonne, S., Coussen, F and Mulle, C. (2000) Kainate receptor-mediated synaptic currents in cerebellar Golgi cells are not shaped by diffusion of glutamate. Proc. Natl. Acad. Sci. USA 97,6838-6843. 

Tia, S., Wang, J. F., Kotchabhakdi, N and Vicini, S. (1996) Developmental changes of inhibitory synaptic currents in cerebellar granule neurons role of GABAa receptor a6 subunit.. /. Neurosci. 16, 3630-3640. 

GABAa receptor al subunit deletion prevents developmental changes of inhibitory synaptic currents in cerebellar neurons../. Neurosci. 21,3009-3016. 

Llano 1, Leresche N, Marty A (1991) Calcium entry increases the sensitivity of cerebellar Purkinje cells to applied GABA and decreases inhibitory synaptic currents. Neuron 6 565-574... 

Physiological studies have identified both post- and presynaptic roles for ionotropic kainate receptors. Kainate receptors contribute to excitatory post-synaptic currents in many regions of the CNS including hippocampus, cortex, spinal cord and retina. In some cases, postsynaptic kainate receptors are codistributed with AMPA and NMDA receptors, but there are also synapses where transmission is mediated exclusively by postsynaptic kainate receptors for example, in the retina at connections made by cones onto off bipolar cells. Extrasynaptically located postsynaptic kainate receptors are most likely activated by spill-over glutamate (Eder et al. 2003). Modulation of transmitter release by presynaptic kainate receptors can occur at both excitatory and inhibitory synapses. The depolarization of nerve terminals by current flow through ionotropic kainate receptors appears sufficient to account for most examples of presynaptic regulation however, a number of studies have provided evidence for metabotropic effects on transmitter release that can be initiated by activation of kainate receptors. The hyperexcitability evoked by locally applied kainate, which is quite effectively reduced by endocannabinoids, is probably mediated preferentially via an activation of postsynaptic kainate receptors (Marsicano et al. 2003). 

Li L., Murphy T. H., Hayden M. R., and Raymond L. A. (2004). Enhanced striatal NR2B-containing jV-methyl-D-aspartate receptor-mediated synaptic currents in a mouse model of Huntington disease. J. Neurophysiol. 92 2738-2746. 

GABAa receptors are another site of action of CPZ (9) in neurons of the central nervous system. Mozrzymas et al. [284] have found that CPZ (9) reduced the amplitude and accelerated the decay of miniature inhibitory post-synaptic currents. Using ultrafast y-aminobutyric acid (GABA) applications and model simulations, they demonstrated that CPZ (9) decreased the binding and increased the unbinding constants of the neurotransmitter to GABAa receptors. 

As indicated above, detection of evoked quantal responses (either through minimal stimulation or paired recordings) provides a suitable setting to determine neurotransmitter release probability and alterations in rate of vesicle fusion. However, in synapses with multiple release sites, such as the calyx of Held, isolation of evoked quantal responses is nearly impossible and truly quantal release is hard to detect except in the case of spontaneous neurotransmission. Therefore, under these conditions, the rate of synaptic vesicle fusion can be determined by deconvolution of synaptic currents with the quantal unitary current. This approach is valid only when the synaptic current can be assumed to result from the convolution between a quantal current and quantal release rates. This assumption is not valid in cases where post-synaptic mechanisms, such as receptor saturation and desensitization, alter quantal events and thus shape synaptic responses during repetitive stimulation (Neher and Sakaba, 2001). 

Umemiya M, Berger AJ (1995) Presynaptic inhibition by serotonin of glycinergic inhibitory synaptic currents in the rat brain stem. J Neurophysiol 73 1192-1201 Usiello A, Baik JH, Rouge-Pont F, Picetti R, Dierich A, LeMeur M, Piazza PV, Borrelli E (2000) Distinct functions of the two isoforms of dopamine D2 receptors. Nature 408 199-203 Vanderschuren LJ, Wardeh G, De Vries TJ, Mulder AH, Schoffelmeer AN (1999) Opposing role of dopamine Di and D2 receptors in modulation of rat nucleus accumbens noradrenaline release. J Neurosci 19 4123-31... 

Mukhtarov M, Ragozzino D, Bregestovski P (2005) Dual Ca2+ modulation of glycinergic synaptic currents in rodent hypoglossal motoneurones. J Physiol 569 817-31 Narasimhan K, Linden DJ (1996) Defining a minimal computational unit for cerebellar long-term... 

---